A member of the Bcl-2 protein family and homologous partner of C-BCL-2 PROTO-ONCOGENE PROTEIN. It regulates the release of CYTOCHROME C and APOPTOSIS INDUCING FACTOR from the MITOCHONDRIA. Several isoforms of BCL2-associated X protein occur due to ALTERNATIVE SPLICING of the mRNA for this protein.
Diffusible gene products that act on homologous or heterologous molecules of viral or cellular DNA to regulate the expression of proteins.
The type species of the genus ORTHOHEPADNAVIRUS which causes human HEPATITIS B and is also apparently a causal agent in human HEPATOCELLULAR CARCINOMA. The Dane particle is an intact hepatitis virion, named after its discoverer. Non-infectious spherical and tubular particles are also seen in the serum.
Antigens of the virion of the HEPATITIS B VIRUS or the Dane particle, its surface (HEPATITIS B SURFACE ANTIGENS), core (HEPATITIS B CORE ANTIGENS), and other associated antigens, including the HEPATITIS B E ANTIGENS.
A primary malignant neoplasm of epithelial liver cells. It ranges from a well-differentiated tumor with EPITHELIAL CELLS indistinguishable from normal HEPATOCYTES to a poorly differentiated neoplasm. The cells may be uniform or markedly pleomorphic, or form GIANT CELLS. Several classification schemes have been suggested.
Tumors or cancer of the LIVER.
Membrane proteins encoded by the BCL-2 GENES and serving as potent inhibitors of cell death by APOPTOSIS. The proteins are found on mitochondrial, microsomal, and NUCLEAR MEMBRANE sites within many cell types. Overexpression of bcl-2 proteins, due to a translocation of the gene, is associated with follicular lymphoma.
A family in the order MONONEGAVIRALES comprising one genus Bornavirus. This family has a unique form of mRNA processing: replication and transcription takes place in the nucleus.
The main structural component of the LIVER. They are specialized EPITHELIAL CELLS that are organized into interconnected plates called lobules.
Processes that stimulate the GENETIC TRANSCRIPTION of a gene or set of genes.
Established cell cultures that have the potential to propagate indefinitely.
A human liver tumor cell line used to study a variety of liver-specific metabolic functions.
One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.
The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.
A RNA-binding protein that is found predominately in the CYTOPLASM. It helps regulate GENETIC TRANSLATION in NEURONS and is absent or under-expressed in FRAGILE X SYNDROME.
An ORTHOHEPADNAVIRUS causing chronic liver disease and hepatocellular carcinoma in woodchucks. It closely resembles the human hepatitis B virus.
Any of the processes by which cytoplasmic factors influence the differential control of gene action in viruses.
Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.
INFLAMMATION of the LIVER in humans caused by a member of the ORTHOHEPADNAVIRUS genus, HEPATITIS B VIRUS. It is primarily transmitted by parenteral exposure, such as transfusion of contaminated blood or blood products, but can also be transmitted via sexual or intimate personal contact.
A genus of Sciuridae consisting of 14 species. They are shortlegged, burrowing rodents which hibernate in winter.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
A species in the genus Bornavirus, family BORNAVIRIDAE, causing a rare and usually fatal encephalitic disease in horses and other domestic animals and possibly deer. Its name derives from the city in Saxony where the condition was first described in 1894, but the disease occurs in Europe, N. Africa, and the Near East.
A cell line derived from cultured tumor cells.
A family of hepatotropic DNA viruses which contains double-stranded DNA genomes and causes hepatitis in humans and animals. There are two genera: AVIHEPADNAVIRUS and ORTHOHEPADNAVIRUS. Hepadnaviruses include HEPATITIS B VIRUS, duck hepatitis B virus (HEPATITIS B VIRUS, DUCK), heron hepatitis B virus, ground squirrel hepatitis virus, and woodchuck hepatitis B virus (HEPATITIS B VIRUS, WOODCHUCK).
DNA sequences which are recognized (directly or indirectly) and bound by a DNA-dependent RNA polymerase during the initiation of transcription. Highly conserved sequences within the promoter include the Pribnow box in bacteria and the TATA BOX in eukaryotes.
An enzyme that catalyzes the acetylation of chloramphenicol to yield chloramphenicol 3-acetate. Since chloramphenicol 3-acetate does not bind to bacterial ribosomes and is not an inhibitor of peptidyltransferase, the enzyme is responsible for the naturally occurring chloramphenicol resistance in bacteria. The enzyme, for which variants are known, is found in both gram-negative and gram-positive bacteria. EC 2.3.1.28.
Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.
The female sex chromosome, being the differential sex chromosome carried by half the male gametes and all female gametes in human and other male-heterogametic species.
Nuclear phosphoprotein encoded by the p53 gene (GENES, P53) whose normal function is to control CELL PROLIFERATION and APOPTOSIS. A mutant or absent p53 protein has been found in LEUKEMIA; OSTEOSARCOMA; LUNG CANCER; and COLORECTAL CANCER.
Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.
The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.
A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.
A secreted phospholipase A2 subtype that contains a interfacial-binding region with specificity for PHOSPHATIDYLCHOLINE. This enzyme group may play a role in eliciting ARACHIDONIC ACID release from intact cellular membranes and from LOW DENSITY LIPOPROTEINS. Members of this group bind specifically to PHOSPHOLIPASE A2 RECEPTORS.
Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.
Extrachromosomal, usually CIRCULAR DNA molecules that are self-replicating and transferable from one organism to another. They are found in a variety of bacterial, archaeal, fungal, algal, and plant species. They are used in GENETIC ENGINEERING as CLONING VECTORS.
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
A broad category of viral proteins that play indirect roles in the biological processes and activities of viruses. Included here are proteins that either regulate the expression of viral genes or are involved in modifying host cell functions. Many of the proteins in this category serve multiple functions.
Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.
Ubiquitous, inducible, nuclear transcriptional activator that binds to enhancer elements in many different cell types and is activated by pathogenic stimuli. The NF-kappa B complex is a heterodimer composed of two DNA-binding subunits: NF-kappa B1 and relA.
The process of intracellular viral multiplication, consisting of the synthesis of PROTEINS; NUCLEIC ACIDS; and sometimes LIPIDS, and their assembly into a new infectious particle.
Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.
The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.
Serologic tests in which a positive reaction manifested by visible CHEMICAL PRECIPITATION occurs when a soluble ANTIGEN reacts with its precipitins, i.e., ANTIBODIES that can form a precipitate.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.
Semiautonomous, self-reproducing organelles that occur in the cytoplasm of all cells of most, but not all, eukaryotes. Each mitochondrion is surrounded by a double limiting membrane. The inner membrane is highly invaginated, and its projections are called cristae. Mitochondria are the sites of the reactions of oxidative phosphorylation, which result in the formation of ATP. They contain distinctive RIBOSOMES, transfer RNAs (RNA, TRANSFER); AMINO ACYL T RNA SYNTHETASES; and elongation and termination factors. Mitochondria depend upon genes within the nucleus of the cells in which they reside for many essential messenger RNAs (RNA, MESSENGER). Mitochondria are believed to have arisen from aerobic bacteria that established a symbiotic relationship with primitive protoeukaryotes. (King & Stansfield, A Dictionary of Genetics, 4th ed)
Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity.
The B-cell leukemia/lymphoma-2 genes, responsible for blocking apoptosis in normal cells, and associated with follicular lymphoma when overexpressed. Overexpression results from the t(14;18) translocation. The human c-bcl-2 gene is located at 18q24 on the long arm of chromosome 18.
Proteins found in any species of virus.
Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (CELL NUCLEOLUS). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the ENDOPLASMIC RETICULUM. A cell may contain more than one nucleus. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)
INFLAMMATION of the LIVER in humans caused by HEPATITIS B VIRUS lasting six months or more. It is primarily transmitted by parenteral exposure, such as transfusion of contaminated blood or blood products, but can also be transmitted via sexual or intimate personal contact.
The parts of a macromolecule that directly participate in its specific combination with another molecule.
A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.
The functional hereditary units of VIRUSES.
The hepatitis B antigen within the core of the Dane particle, the infectious hepatitis virion.
A large multisubunit complex that plays an important role in the degradation of most of the cytosolic and nuclear proteins in eukaryotic cells. It contains a 700-kDa catalytic sub-complex and two 700-kDa regulatory sub-complexes. The complex digests ubiquitinated proteins and protein activated via ornithine decarboxylase antizyme.
A member of the bcl-2 protein family that plays a role in the regulation of APOPTOSIS. Two major isoforms of the protein exist due to ALTERNATIVE SPLICING of the BCL2L1 mRNA and are referred to as Bcl-XS and Bcl-XL.
All of the processes involved in increasing CELL NUMBER including CELL DIVISION.
A positive regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.
A transcription factor that regulates the expression of a large set of hepatic proteins including SERUM ALBUMIN; beta-fibrinogen; and ALPHA 1-ANTITRYPSIN. It is composed of hetero- or homo-dimers of HEPATOCYTE NUCLEAR FACTOR 1-ALPHA and HEPATOCYTE NUCLEAR FACTOR 1-BETA.
A negative regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.
Proteins found in the nucleus of a cell. Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus.
Small double-stranded, non-protein coding RNAs (21-31 nucleotides) involved in GENE SILENCING functions, especially RNA INTERFERENCE (RNAi). Endogenously, siRNAs are generated from dsRNAs (RNA, DOUBLE-STRANDED) by the same ribonuclease, Dicer, that generates miRNAs (MICRORNAS). The perfect match of the siRNAs' antisense strand to their target RNAs mediates RNAi by siRNA-guided RNA cleavage. siRNAs fall into different classes including trans-acting siRNA (tasiRNA), repeat-associated RNA (rasiRNA), small-scan RNA (scnRNA), and Piwi protein-interacting RNA (piRNA) and have different specific gene silencing functions.
A family of intracellular signaling adaptor proteins that contain caspase activation and recruitment domains. Proteins that contain this domain play a role in APOPTOSIS-related signal transduction by associating with other CARD domain-containing members and in activating INITIATOR CASPASES that contain CARD domains within their N-terminal pro-domain region.
Screening techniques first developed in yeast to identify genes encoding interacting proteins. Variations are used to evaluate interplay between proteins and other molecules. Two-hybrid techniques refer to analysis for protein-protein interactions, one-hybrid for DNA-protein interactions, three-hybrid interactions for RNA-protein interactions or ligand-based interactions. Reverse n-hybrid techniques refer to analysis for mutations or other small molecules that dissociate known interactions.
Deoxyribonucleic acid that makes up the genetic material of viruses.
A type of chromosome aberration characterized by CHROMOSOME BREAKAGE and transfer of the broken-off portion to another location, often to a different chromosome.
The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in neoplastic tissue.
A gene silencing phenomenon whereby specific dsRNAs (RNA, DOUBLE-STRANDED) trigger the degradation of homologous mRNA (RNA, MESSENGER). The specific dsRNAs are processed into SMALL INTERFERING RNA (siRNA) which serves as a guide for cleavage of the homologous mRNA in the RNA-INDUCED SILENCING COMPLEX. DNA METHYLATION may also be triggered during this process.
A group of heterogeneous lymphoid tumors generally expressing one or more B-cell antigens or representing malignant transformations of B-lymphocytes.
A short pro-domain caspase that plays an effector role in APOPTOSIS. It is activated by INITIATOR CASPASES such as CASPASE 9. Isoforms of this protein exist due to multiple alternative splicing of its MESSENGER RNA.
A family of intracellular CYSTEINE ENDOPEPTIDASES that play a role in regulating INFLAMMATION and APOPTOSIS. They specifically cleave peptides at a CYSTEINE amino acid that follows an ASPARTIC ACID residue. Caspases are activated by proteolytic cleavage of a precursor form to yield large and small subunits that form the enzyme. Since the cleavage site within precursors matches the specificity of caspases, sequential activation of precursors by activated caspases can occur.
Cis-acting DNA sequences which can increase transcription of genes. Enhancers can usually function in either orientation and at various distances from a promoter.
A condition characterized genotypically by mutation of the distal end of the long arm of the X chromosome (at gene loci FRAXA or FRAXE) and phenotypically by cognitive impairment, hyperactivity, SEIZURES, language delay, and enlargement of the ears, head, and testes. INTELLECTUAL DISABILITY occurs in nearly all males and roughly 50% of females with the full mutation of FRAXA. (From Menkes, Textbook of Child Neurology, 5th ed, p226)
A specific pair of GROUP D CHROMOSOMES of the human chromosome classification.
The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for VIRUS CULTIVATION and antitumor drug screening assays.
Genes whose expression is easily detectable and therefore used to study promoter activity at many positions in a target genome. In recombinant DNA technology, these genes may be attached to a promoter region of interest.
The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.
Hepatocyte nuclear factor 1-alpha is a transcription factor found in the LIVER; PANCREAS; and KIDNEY that regulates HOMEOSTASIS of GLUCOSE.
Malignant lymphoma composed of large B lymphoid cells whose nuclear size can exceed normal macrophage nuclei, or more than twice the size of a normal lymphocyte. The pattern is predominantly diffuse. Most of these lymphomas represent the malignant counterpart of B-lymphocytes at midstage in the process of differentiation.
Enzymes that oxidize certain LUMINESCENT AGENTS to emit light (PHYSICAL LUMINESCENCE). The luciferases from different organisms have evolved differently so have different structures and substrates.
A member of the Bcl-2 protein family that reversibly binds MEMBRANES. It is a pro-apoptotic protein that is activated by caspase cleavage.
The activated center of a lymphoid follicle in secondary lymphoid tissue where B-LYMPHOCYTES are stimulated by antigens and helper T cells (T-LYMPHOCYTES, HELPER-INDUCER) are stimulated to generate memory cells.
Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.
Single-stranded complementary DNA synthesized from an RNA template by the action of RNA-dependent DNA polymerase. cDNA (i.e., complementary DNA, not circular DNA, not C-DNA) is used in a variety of molecular cloning experiments as well as serving as a specific hybridization probe.
A protein that has been shown to function as a calcium-regulated transcription factor as well as a substrate for depolarization-activated CALCIUM-CALMODULIN-DEPENDENT PROTEIN KINASES. This protein functions to integrate both calcium and cAMP signals.
A specific pair of GROUP E CHROMOSOMES of the human chromosome classification.
Histochemical localization of immunoreactive substances using labeled antibodies as reagents.
Storage-stable glycoprotein blood coagulation factor that can be activated to factor Xa by both the intrinsic and extrinsic pathways. A deficiency of factor X, sometimes called Stuart-Prower factor deficiency, may lead to a systemic coagulation disorder.
In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships.
Proteins prepared by recombinant DNA technology.
Methods used for detecting the amplified DNA products from the polymerase chain reaction as they accumulate instead of at the end of the reaction.
The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.
Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.
Transport proteins that carry specific substances in the blood or across cell membranes.
Cell changes manifested by escape from control mechanisms, increased growth potential, alterations in the cell surface, karyotypic abnormalities, morphological and biochemical deviations from the norm, and other attributes conferring the ability to invade, metastasize, and kill.
Eukaryotic cell line obtained in a quiescent or stationary phase which undergoes conversion to a state of unregulated growth in culture, resembling an in vitro tumor. It occurs spontaneously or through interaction with viruses, oncogenes, radiation, or drugs/chemicals.
ENDOPEPTIDASES which have a cysteine involved in the catalytic process. This group of enzymes is inactivated by CYSTEINE PROTEINASE INHIBITORS such as CYSTATINS and SULFHYDRYL REAGENTS.
Proteins obtained from foods. They are the main source of the ESSENTIAL AMINO ACIDS.
Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake.
The determination of the pattern of genes expressed at the level of GENETIC TRANSCRIPTION, under specific circumstances or in a specific cell.
Elements of limited time intervals, contributing to particular results or situations.
The complex series of phenomena, occurring between the end of one CELL DIVISION and the end of the next, by which cellular material is duplicated and then divided between two daughter cells. The cell cycle includes INTERPHASE, which includes G0 PHASE; G1 PHASE; S PHASE; and G2 PHASE, and CELL DIVISION PHASE.
Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.
Use of restriction endonucleases to analyze and generate a physical map of genomes, genes, or other segments of DNA.
Systems of enzymes which function sequentially by catalyzing consecutive reactions linked by common metabolic intermediates. They may involve simply a transfer of water molecules or hydrogen atoms and may be associated with large supramolecular structures such as MITOCHONDRIA or RIBOSOMES.
The part of a cell that contains the CYTOSOL and small structures excluding the CELL NUCLEUS; MITOCHONDRIA; and large VACUOLES. (Glick, Glossary of Biochemistry and Molecular Biology, 1990)
The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.
The complete genetic complement contained in a DNA or RNA molecule in a virus.
The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.
Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.
A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.
A species of POLYOMAVIRUS originally isolated from Rhesus monkey kidney tissue. It produces malignancy in human and newborn hamster kidney cell cultures.
The rate dynamics in chemical or physical systems.
Proteins that bind to RNA molecules. Included here are RIBONUCLEOPROTEINS and other proteins whose function is to bind specifically to RNA.
Proteins that originate from insect species belonging to the genus DROSOPHILA. The proteins from the most intensely studied species of Drosophila, DROSOPHILA MELANOGASTER, are the subject of much interest in the area of MORPHOGENESIS and development.
Mutant mice homozygous for the recessive gene "nude" which fail to develop a thymus. They are useful in tumor studies and studies on immune responses.
The biosynthesis of PEPTIDES and PROTEINS on RIBOSOMES, directed by MESSENGER RNA, via TRANSFER RNA that is charged with standard proteinogenic AMINO ACIDS.
Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.
Sequences of DNA or RNA that occur in multiple copies. There are several types: INTERSPERSED REPETITIVE SEQUENCES are copies of transposable elements (DNA TRANSPOSABLE ELEMENTS or RETROELEMENTS) dispersed throughout the genome. TERMINAL REPEAT SEQUENCES flank both ends of another sequence, for example, the long terminal repeats (LTRs) on RETROVIRUSES. Variations may be direct repeats, those occurring in the same direction, or inverted repeats, those opposite to each other in direction. TANDEM REPEAT SEQUENCES are copies which lie adjacent to each other, direct or inverted (INVERTED REPEAT SEQUENCES).
Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.
Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.
The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability.
A broad category of carrier proteins that play a role in SIGNAL TRANSDUCTION. They generally contain several modular domains, each of which having its own binding activity, and act by forming complexes with other intracellular-signaling molecules. Signal-transducing adaptor proteins lack enzyme activity, however their activity can be modulated by other signal-transducing enzymes
The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.
Proteins whose abnormal expression (gain or loss) are associated with the development, growth, or progression of NEOPLASMS. Some neoplasm proteins are tumor antigens (ANTIGENS, NEOPLASM), i.e. they induce an immune reaction to their tumor. Many neoplasm proteins have been characterized and are used as tumor markers (BIOMARKERS, TUMOR) when they are detectable in cells and body fluids as monitors for the presence or growth of tumors. Abnormal expression of ONCOGENE PROTEINS is involved in neoplastic transformation, whereas the loss of expression of TUMOR SUPPRESSOR PROTEINS is involved with the loss of growth control and progression of the neoplasm.
Malignant lymphoma in which the lymphomatous cells are clustered into identifiable nodules within the LYMPH NODES. The nodules resemble to some extent the GERMINAL CENTER of lymph node follicles and most likely represent neoplastic proliferation of lymph node-derived follicular center B-LYMPHOCYTES.
Proteins which maintain the transcriptional quiescence of specific GENES or OPERONS. Classical repressor proteins are DNA-binding proteins that are normally bound to the OPERATOR REGION of an operon, or the ENHANCER SEQUENCES of a gene until a signal occurs that causes their release.
Ribonucleic acid that makes up the genetic material of viruses.
Lymphoid cells concerned with humoral immunity. They are short-lived cells resembling bursa-derived lymphocytes of birds in their production of immunoglobulin upon appropriate stimulation.
The ordered rearrangement of gene regions by DNA recombination such as that which occurs normally during development.
Members of the beta-globin family. In humans, two non-allelic types of gamma-globin - A gamma and G gamma are encoded in the beta-globin gene cluster on CHROMOSOME 11. Two gamma-globin chains combine with two ZETA-GLOBIN chains to form the embryonic hemoglobin Portland. Fetal HEMOGLOBIN F is formed from two gamma-globin chains combined with two ALPHA-GLOBIN chains.
A type of IN SITU HYBRIDIZATION in which target sequences are stained with fluorescent dye so their location and size can be determined using fluorescence microscopy. This staining is sufficiently distinct that the hybridization signal can be seen both in metaphase spreads and in interphase nuclei.
A subtype of RETINOIC ACID RECEPTORS that are specific for 9-cis-retinoic acid which function as nuclear TRANSCRIPTION FACTORS that regulate multiple signaling pathways.
Extranodal lymphoma of lymphoid tissue associated with mucosa that is in contact with exogenous antigens. Many of the sites of these lymphomas, such as the stomach, salivary gland, and thyroid, are normally devoid of lymphoid tissue. They acquire mucosa-associated lymphoid tissue (MALT) type as a result of an immunologically mediated disorder.
A specific pair of human chromosomes in group A (CHROMOSOMES, HUMAN, 1-3) of the human chromosome classification.
A member of the myeloid leukemia factor (MLF) protein family with multiple alternatively spliced transcript variants encoding different protein isoforms. In hematopoietic cells, it is located mainly in the nucleus, and in non-hematopoietic cells, primarily in the cytoplasm with a punctate nuclear localization. MLF1 plays a role in cell cycle differentiation.
Genes and gene segments encoding the IMMUNOGLOBULIN HEAVY CHAINS. Gene segments of the heavy chain genes are symbolized V (variable), D (diversity), J (joining), and C (constant).
Lymphocyte progenitor cells that are restricted in their differentiation potential to the B lymphocyte lineage. The pro-B cell stage of B lymphocyte development precedes the pre-B cell stage.
A malignant disease of the B-LYMPHOCYTES in the bone marrow and/or blood.
The largest of polypeptide chains comprising immunoglobulins. They contain 450 to 600 amino acid residues per chain, and have molecular weights of 51-72 kDa.
Normal cellular genes homologous to viral oncogenes. The products of proto-oncogenes are important regulators of biological processes and appear to be involved in the events that serve to maintain the ordered procession through the cell cycle. Proto-oncogenes have names of the form c-onc.
The type species of the genus MICROVIRUS. A prototype of the small virulent DNA coliphages, it is composed of a single strand of supercoiled circular DNA, which on infection, is converted to a double-stranded replicative form by a host enzyme.
Family of retrovirus-associated DNA sequences (myc) originally isolated from an avian myelocytomatosis virus. The proto-oncogene myc (c-myc) codes for a nuclear protein which is involved in nucleic acid metabolism and in mediating the cellular response to growth factors. Truncation of the first exon, which appears to regulate c-myc expression, is crucial for tumorigenicity. The human c-myc gene is located at 8q24 on the long arm of chromosome 8.
An increase in circulating RETICULOCYTES, which is among the simplest and most reliable signs of accelerated ERYTHROCYTE production. Reticulocytosis occurs during active BLOOD regeneration (stimulation of red bone marrow) and in certain types of ANEMIA, particularly CONGENITAL HEMOLYTIC ANEMIA.
Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.
Lymphocyte progenitor cells that are restricted in their differentiation potential to the T lymphocyte lineage.
Enzyme that is a major constituent of kidney brush-border membranes and is also present to a lesser degree in the brain and other tissues. It preferentially catalyzes cleavage at the amino group of hydrophobic residues of the B-chain of insulin as well as opioid peptides and other biologically active peptides. The enzyme is inhibited primarily by EDTA, phosphoramidon, and thiorphan and is reactivated by zinc. Neprilysin is identical to common acute lymphoblastic leukemia antigen (CALLA Antigen), an important marker in the diagnosis of human acute lymphocytic leukemia. There is no relationship with CALLA PLANT.
A chronic leukemia characterized by abnormal B-lymphocytes and often generalized lymphadenopathy. In patients presenting predominately with blood and bone marrow involvement it is called chronic lymphocytic leukemia (CLL); in those predominately with enlarged lymph nodes it is called small lymphocytic lymphoma. These terms represent spectrums of the same disease.
A class of cell surface receptors for PURINES that prefer ATP or ADP over ADENOSINE. P2 purinergic receptors are widespread in the periphery and in the central and peripheral nervous system.
The major component of hemoglobin in the fetus. This HEMOGLOBIN has two alpha and two gamma polypeptide subunits in comparison to normal adult hemoglobin, which has two alpha and two beta polypeptide subunits. Fetal hemoglobin concentrations can be elevated (usually above 0.5%) in children and adults affected by LEUKEMIA and several types of ANEMIA.
The middle piece of the spermatozoon is a highly organized segment consisting of MITOCHONDRIA, the outer dense fibers and the core microtubular structure.
Proteins that are normally involved in holding cellular growth in check. Deficiencies or abnormalities in these proteins may lead to unregulated cell growth and tumor development.
A cyclin D subtype which is regulated by GATA4 TRANSCRIPTION FACTOR. Experiments using KNOCKOUT MICE suggest a role for cyclin D2 in granulosa cell proliferation and gonadal development.
Cellular DNA-binding proteins encoded by the c-myc genes. They are normally involved in nucleic acid metabolism and in mediating the cellular response to growth factors. Elevated and deregulated (constitutive) expression of c-myc proteins can cause tumorigenesis.
A type of chromosomal aberration involving DNA BREAKS. Chromosome breakage can result in CHROMOSOMAL TRANSLOCATION; CHROMOSOME INVERSION; or SEQUENCE DELETION.
Ordered rearrangement of B-lymphocyte variable gene regions coding for the IMMUNOGLOBULIN CHAINS, thereby contributing to antibody diversity. It occurs during the differentiation of the IMMATURE B-LYMPHOCYTES.
A subclass of caspases that contain short pro-domain regions. They are activated by the proteolytic action of INITIATOR CASPASES. Once activated they cleave a variety of substrates that cause APOPTOSIS.
Hybridization of a nucleic acid sample to a very large set of OLIGONUCLEOTIDE PROBES, which have been attached individually in columns and rows to a solid support, to determine a BASE SEQUENCE, or to detect variations in a gene sequence, GENE EXPRESSION, or for GENE MAPPING.
A family of transcription factors that share an N-terminal HELIX-TURN-HELIX MOTIF and bind INTERFERON-inducible promoters to control GENE expression. IRF proteins bind specific DNA sequences such as interferon-stimulated response elements, interferon regulatory elements, and the interferon consensus sequence.
A specific pair of GROUP C CHROMOSOMES of the human chromosome classification.
A prediction of the probable outcome of a disease based on a individual's condition and the usual course of the disease as seen in similar situations.
Molecular products metabolized and secreted by neoplastic tissue and characterized biochemically in cells or body fluids. They are indicators of tumor stage and grade as well as useful for monitoring responses to treatment and predicting recurrence. Many chemical groups are represented including hormones, antigens, amino and nucleic acids, enzymes, polyamines, and specific cell membrane proteins and lipids.
Regions along polytene chromosomes that are uncondensed and active in DNA REPLICATION or RNA transcription (GENETIC TRANSCRIPTION).
Process of classifying cells of the immune system based on structural and functional differences. The process is commonly used to analyze and sort T-lymphocytes into subsets based on CD antigens by the technique of flow cytometry.
Blood coagulation disorder usually inherited as an autosomal recessive trait, though it can be acquired. It is characterized by defective activity in both the intrinsic and extrinsic pathways, impaired thromboplastin time, and impaired prothrombin consumption.
A nuclear co-repressor protein that shows specificity for RETINOIC ACID RECEPTORS and THYROID HORMONE RECEPTORS. The dissociation of this co-repressor from nuclear receptors is generally ligand-dependent, but can also occur by way of its phosphorylation by members of the MAP KINASE SIGNALING SYSTEM. The protein contains two nuclear receptor interaction domains and four repressor domains and is closely-related in structure to NUCLEAR RECEPTOR CO-REPRESSOR 1.
Antibodies obtained from a single clone of cells grown in mice or rats.
A cell line generated from human embryonic kidney cells that were transformed with human adenovirus type 5.
A CELL LINE derived from human T-CELL LEUKEMIA and used to determine the mechanism of differential susceptibility to anti-cancer drugs and radiation.
Genes encoding the different subunits of the IMMUNOGLOBULINS, for example the IMMUNOGLOBULIN LIGHT CHAIN GENES and the IMMUNOGLOBULIN HEAVY CHAIN GENES. The heavy and light immunoglobulin genes are present as gene segments in the germline cells. The completed genes are created when the segments are shuffled and assembled (B-LYMPHOCYTE GENE REARRANGEMENT) during B-LYMPHOCYTE maturation. The gene segments of the human light and heavy chain germline genes are symbolized V (variable), J (joining) and C (constant). The heavy chain germline genes have an additional segment D (diversity).
Ordered rearrangement of B-lymphocyte variable gene regions of the IMMUNOGLOBULIN HEAVY CHAINS, thereby contributing to antibody diversity. It occurs during the first stage of differentiation of the IMMATURE B-LYMPHOCYTES.
The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.
A member of the beta-globin family. In humans, delta-globin is encoded in the beta-globin gene cluster located on CHROMOSOME 11. Two delta-globin chains along with two alpha-globin chains form HEMOGLOBIN A2 which makes up about 3% of the HEMOGLOBIN in adults.
A protein serine-threonine kinase that catalyzes the PHOSPHORYLATION of I KAPPA B PROTEINS. This enzyme also activates the transcription factor NF-KAPPA B and is composed of alpha and beta catalytic subunits, which are protein kinases and gamma, a regulatory subunit.
The GENETIC TRANSLATION products of the fusion between an ONCOGENE and another gene. The latter may be of viral or cellular origin.
A general term for various neoplastic diseases of the lymphoid tissue.
Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.
Any of a group of malignant tumors of lymphoid tissue that differ from HODGKIN DISEASE, being more heterogeneous with respect to malignant cell lineage, clinical course, prognosis, and therapy. The only common feature among these tumors is the absence of giant REED-STERNBERG CELLS, a characteristic of Hodgkin's disease.
A leukemia/lymphoma found predominately in children and young adults and characterized LYMPHADENOPATHY and THYMUS GLAND involvement. It most frequently presents as a lymphoma, but a leukemic progression in the bone marrow is common.
A multi-domain mitochondrial membrane protein and member of the bcl-2 Protein family. Bak protein interacts with TUMOR SUPPRESSOR PROTEIN P53 and promotes APOPTOSIS.
DNA present in neoplastic tissue.
Members of the beta-globin family. In humans, they are encoded in a gene cluster on CHROMOSOME 11. They include epsilon-globin, gamma-globin, delta-globin and beta-globin. There is also a pseudogene of beta (theta-beta) in the gene cluster. Adult HEMOGLOBIN is comprised of two ALPHA-GLOBIN chains and two beta-globin chains.
A group of compounds that contain the structure SO2NH2.
A single nucleotide variation in a genetic sequence that occurs at appreciable frequency in the population.
Genes whose gain-of-function alterations lead to NEOPLASTIC CELL TRANSFORMATION. They include, for example, genes for activators or stimulators of CELL PROLIFERATION such as growth factors, growth factor receptors, protein kinases, signal transducers, nuclear phosphoproteins, and transcription factors. A prefix of "v-" before oncogene symbols indicates oncogenes captured and transmitted by RETROVIRUSES; the prefix "c-" before the gene symbol of an oncogene indicates it is the cellular homolog (PROTO-ONCOGENES) of a v-oncogene.
A technique for identifying specific DNA sequences that are bound, in vivo, to proteins of interest. It involves formaldehyde fixation of CHROMATIN to crosslink the DNA-BINDING PROTEINS to the DNA. After shearing the DNA into small fragments, specific DNA-protein complexes are isolated by immunoprecipitation with protein-specific ANTIBODIES. Then, the DNA isolated from the complex can be identified by PCR amplification and sequencing.
A short pro-domain caspase that plays an effector role in APOPTOSIS. It is activated by INITIATOR CASPASES such as CASPASE 3 and CASPASE 10. Several isoforms of this protein exist due to multiple alternative splicing of its MESSENGER RNA.
Lymphocytes responsible for cell-mediated immunity. Two types have been identified - cytotoxic (T-LYMPHOCYTES, CYTOTOXIC) and helper T-lymphocytes (T-LYMPHOCYTES, HELPER-INDUCER). They are formed when lymphocytes circulate through the THYMUS GLAND and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen.
Motifs in DNA- and RNA-binding proteins whose amino acids are folded into a single structural unit around a zinc atom. In the classic zinc finger, one zinc atom is bound to two cysteines and two histidines. In between the cysteines and histidines are 12 residues which form a DNA binding fingertip. By variations in the composition of the sequences in the fingertip and the number and spacing of tandem repeats of the motif, zinc fingers can form a large number of different sequence specific binding sites.
CXCR receptors isolated initially from BURKITT LYMPHOMA cells. CXCR5 receptors are expressed on mature, recirculating B-LYMPHOCYTES and are specific for CHEMOKINE CXCL13.
Substances that inhibit or prevent the proliferation of NEOPLASMS.
A pro-apoptotic protein and member of the Bcl-2 protein family that is regulated by PHOSPHORYLATION. Unphosphorylated Bad protein inhibits the activity of BCL-XL PROTEIN.

A photodynamic pathway to apoptosis and necrosis induced by dimethyl tetrahydroxyhelianthrone and hypericin in leukaemic cells: possible relevance to photodynamic therapy. (1/4256)

The mechanism of cell death induction by dimethyl tetrahydroxyhelianthrone (DTHe), a new second-generation photodynamic sensitizer, is analysed in human leukaemic cell lines in comparison with the structurally related hypericin. DTHe has a broad range of light spectrum absorption that enables effective utilization of polychromatic light. Photosensitization of HL-60 cells with low doses of DTHe (0.65 microM DTHe and 7.2 J cm(-2) light energy) induced rapid apoptosis of > or =90% of the cells. At doses > or =2 microM, dying cells assumed morphological necrosis with perinucleolar condensation of chromatin in HL-60 and K-562 cell lines. Although nuclear fragmentation that is characteristic to apoptosis was prevented, DNA digestion to oligonucleosomes proceeded unhindered. Such incomplete apoptosis was more prevalent with the related analogue hypericin throughout most doses of photosensitization. Despite hypericin being a stronger photosensitizer, DTHe exhibited advantageous phototoxic properties to tumour cells, initiating apoptosis at concentrations about threefold lower than hypericin. Photosensitization of the cells induced dissociation of the nuclear envelope, releasing lamins into the cytosol. DTHe also differed from hypericin in effects exerted on the nuclear lamina, causing release of an 86-kDa lamin protein into the cytosol that was unique to DTHe. Within the nucleus, nuclear envelope lamin B underwent covalent polymerization, which did not affect apoptotic nuclear fragmentation at low doses of DTHe. At higher doses, polymerization may have been extensive enough to prevent nuclear collapse. Hut-78, CD4+ cells were resistant to the photodynamically activated apoptotic pathway. Beyond the tolerated levels of photodynamic damage, these cells died exclusively via necrosis. Hut-78 cells overexpress Bcl-X(L) as well as a truncated Bcl-X(L)tr isoform that could contribute to the observed resistance to apoptosis.  (+info)

Microsatellite instability, Epstein-Barr virus, mutation of type II transforming growth factor beta receptor and BAX in gastric carcinomas in Hong Kong Chinese. (2/4256)

Microsatellite instability (MI), the phenotypic manifestation of mismatch repair failure, is found in a proportion of gastric carcinomas. Little is known of the links between MI and Epstein-Barr virus (EBV) status and clinicopathological elements. Examination of genes mutated through the MI mechanism could also be expected to reveal important information on the carcinogenic pathway. Seventy-nine gastric carcinomas (61 EBV negative, 18 EBV positive) from local Hong Kong Chinese population, an intermediate-incidence area, were examined. Eight microsatellite loci, inclusive of the A10 tract of type II transforming growth factor beta receptor (TbetaR-II), were used to evaluate the MI status. MI in the BAX and insulin-like growth factor II receptor (IGF-IIR) genes were also examined. High-level MI (>40% unstable loci) was detected in ten cases (12.7%) and low-level MI (1-40% unstable loci) in three (3.8%). High-level MI was detected in two EBV-associated cases (11%) and the incidence was similar for the EBV-negative cases (13%). The high-level MIs were significantly associated with intestinal-type tumours (P = 0.03) and a more prominent lymphoid infiltrate (P = 0.04). Similar associations were noted in the EBV-positive carcinomas. The high-level MIs were more commonly located in the antrum, whereas the EBV-associated carcinomas were mostly located in body. Thirteen cardia cases were negative for both high-level MI and EBV. All patients aged below 55 were MI negative (P = 0.049). Of the high-level MIs, 80% had mutation in TbetaR-II, 40% in BAX and 0% in IGF-IIR. Of low-level MIs, 33% also had TbetaR-II mutation. These mutations were absent in the MI-negative cases. Of three lymphoepithelioma-like carcinomas, two cases were EBV positive and MI negative, one case was EBV negative but with high-level MI. In conclusion, high-level MIs were present regardless of the EBV status, and were found in a particular clinicopathological subset of gastric carcinoma patient. Inactivation of important growth regulatory genes observed in these carcinomas confirms the importance of MI in carcinogenesis.  (+info)

Role of hypoxia-induced Bax translocation and cytochrome c release in reoxygenation injury. (3/4256)

We investigated mechanisms of cell death during hypoxia/reoxygenation of cultured kidney cells. During glucose-free hypoxia, cell ATP levels declined steeply resulting in the translocation of Bax from cytosol to mitochondria. Concurrently, there was cytochrome c release and caspase activation. Cells that leaked cytochrome c underwent apoptosis after reoxygenation. ATP depletion induced by a mitochondrial uncoupler resulted in similar alterations even in the presence of oxygen. Moreover, inclusion of glucose during hypoxia prevented protein translocations and reoxygenation injury by maintaining intracellular ATP. Thus, ATP depletion, rather than hypoxia per se, was the cause of protein translocations. Overexpression of Bcl-2 prevented cytochrome c release and reoxygenation injury without ameliorating ATP depletion or Bax translocation. On the other hand, caspase inhibitors did not prevent protein translocations, but inhibited apoptosis during reoxygenation. Nevertheless, they could not confer long-term viability, since mitochondria had been damaged. Omission of glucose during reoxygenation resulted in continued failure of ATP production, and cell death with necrotic morphology. In contrast, cells expressing Bcl-2 had functional mitochondria and remained viable during reoxygenation even without glucose. Therefore, Bax translocation during hypoxia is a molecular trigger for cell death during reoxygenation. If ATP is available during reoxygenation, apoptosis develops; otherwise, death occurs by necrosis. By preserving mitochondrial integrity, BCL-2 prevents both forms of cell death and ensures cell viability.  (+info)

Apoptosis during breast carcinoma progression. (4/4256)

The purpose of this study was to investigate apoptosis, proliferation, and the expression of apoptosis-influencing proteins bcl-2 and bax and estrogen and progesterone receptors during breast carcinoma progression. The material consisted of 53 paired breast carcinoma samples representing primary and recurrent tumors and 24 control samples. The recurrent sample was located either in the breast scar tissue or at a distant metastatic site. Apoptosis was detected both morphologically and by 3' end labeling of fragmented DNA. Cell proliferation was evaluated immunohistochemically by the MIB index. The expressions of bcl-2, bax, and estrogen and progesterone receptors were studied immunohistochemically. There was a significant increase in the extent of apoptosis and proliferation in recurrent tumors compared to the primary lesions (P = 0.015 and P = 0.038, respectively). In primary tumors with an apoptotic index of >0.50%, the survival of the patients was significantly shorter (P = 0.015). In cases with a significant increase in apoptosis or proliferation in the recurrent tumor, the survival of the patients was significantly shorter (P = 0.009 and P = 0.003, respectively). Of the variables analyzed, bcl-2 expression and a positive estrogen receptor status were significantly associated with a low extent of apoptosis (P = 0.010 and P = 0.042, respectively). Their changes were parallel to the changes in apoptosis during tumor progression, although the associations did not reach statistical significance. The results show that increased apoptosis is associated with a worse prognosis in breast carcinoma. A significant increase in apoptosis in recurrent breast carcinoma lesions predicts a worse clinical outcome.  (+info)

Expression of apoptosis-related genes in human head and neck squamous cell carcinomas undergoing p53-mediated programmed cell death. (5/4256)

Human head and neck squamous cell carcinoma (HNSCC) lines infected with a replication-defective Ad5CMV-p53 vector bearing a wild-type human p53 gene were used to examine alterations in the production of proteins implicated in regulating apoptosis. Because HNSCC lines express abundant levels of c-myc, and simultaneous expression of c-myc and p53 is known to trigger apoptosis in other cells, cooperation between these two genes was examined. Surprisingly, levels of c-myc mRNA and protein were rapidly and profoundly suppressed after infection with wild-type p53. Suppression of c-myc using antisense oligodeoxynucleotides (in the absence of p53) was sufficient to trigger apoptosis in Tu-138 cells, raising the possibility that the reduction of c-myc may be involved in at least one of the cell death pathways mediated by p53. Expression of a panel of Bcl-2 homology proteins was also examined in HNSCC lines undergoing p53-mediated apoptosis. No changes in Bcl-2, Bak, or Bcl-xS were found after p53 expression. Increased levels of the apoptosis-accelerating protein Bax were found in HNSCC lines after infection with Ad5CMV-p53. Induction of the apoptosis-inhibiting protein Bcl-xL was observed in Tu-167 cells and may account for the delayed onset of apoptosis in these cells. These studies suggest that multiple pathways may regulate apoptosis after transient overexpression of p53.  (+info)

Long term lithium treatment suppresses p53 and Bax expression but increases Bcl-2 expression. A prominent role in neuroprotection against excitotoxicity. (6/4256)

This study was undertaken to investigate the molecular mechanisms underlying the neuroprotective actions of lithium against glutamate excitotoxicity with a focus on the role of proapoptotic and antiapoptotic genes. Long term, but not acute, treatment of cultured cerebellar granule cells with LiCl induces a concentration-dependent decrease in mRNA and protein levels of proapoptotic p53 and Bax; conversely, mRNA and protein levels of cytoprotective Bcl-2 are remarkably increased. The ratios of Bcl-2/Bax protein levels increase by approximately 5-fold after lithium treatment for 5-7 days. Exposure of cerebellar granule cells to glutamate induces a rapid increase in p53 and Bax mRNA and protein levels with no apparent effect on Bcl-2 expression. Pretreatment with LiCl for 7 days prevents glutamate-induced increase in p53 and Bax expression and maintains Bcl-2 in an elevated state. Glutamate exposure also triggers the release of cytochrome c from the mitochondria into the cytosol. Lithium pretreatment blocks glutamate-induced cytochrome c release and cleavage of lamin B1, a nuclear substrate for caspase-3. These results strongly suggest that lithium-induced Bcl-2 up-regulation and p53 and Bax down-regulation play a prominent role in neuroprotection against excitotoxicity. Our results further suggest that lithium, in addition to its use in the treatment of bipolar depressive illness, may have an expanded use in the intervention of neurodegeneration.  (+info)

Expression of bcl-2 and bax in glomerular disease. (7/4256)

Bcl-2 may account in part for the maintenance of hypercellularity in human glomerular diseases through preventing cell death and by counteracting bax which may be expressed to regulate excessive proliferation. This process is associated with the effect of PDGF B-chain expression. Bax expression may be important in the cell loss leading to glomerulosclerosis and TGF-beta1 participates in this process by increasing bax expression. Thus, the balance of bcl-2/bax expression may be critical in the course of human glomerular diseases.  (+info)

MycN sensitizes neuroblastoma cells for drug-induced apoptosis. (8/4256)

Amplification of the MYCN gene is found in a large proportion of neuroblastoma and considered as an adverse prognostic factor. To investigate the effect of ectopic MycN expression on the susceptibility of neuroblastoma cells to cytotoxic drugs we used a human neuroblastoma cell line harboring tetracycline-controlled expression of MycN. Neither conditional expression of MycN alone nor low drug concentrations triggered apoptosis. However, when acting in concert, MycN and cytotoxic drugs efficiently induced cell death. Apoptosis depended on mitochondrial permeability transition and activation of caspases, since the mitochondrion-specific inhibitor bongkrekic acid and the caspase inhibitor zVAD-fmk almost completely abrogated apoptosis. Loss of mitochondrial transmembrane potential and release of cytochrome c from mitochondria preceded activation of caspase-8 and caspase-3 and cleavage of PARP. CD95 expression was upregulated by treatment with cytotoxic drugs, while MycN cooperated with cytotoxic drugs to increase sensitivity to CD95-induced apoptosis and enhancing CD95-L expression. MycN overexpression and cytotoxic drugs also synergized to induce p53 and Bax protein expression, while Bcl-2 and Bcl-X(L) protein levels remained unchanged. Since amplification of MYCN is usually associated with a poor prognosis, these findings suggest that dysfunctions in apoptosis pathways may be a mechanism by which MycN-induced apoptosis of neuroblastoma cells is inhibited.  (+info)

The pro-apoptotic protein Bax plays a key role in the mitochondrial signalling pathway. Upon induction of apoptosis, Bax undergoes a conformational change and translocates to mitochondrial membranes, where it inserts and mediates the release of cytochrome c from the intermembrane space into the cytosol. However, the domains of Bax that are essential for the induction of cytochrome c release are still elusive. Therefore various Bax deletion mutants were generated and expressed in Escherichia coli. The proteins were then purified in order to delineate the function of the transmembrane domain, the BH3 (Bcl-2 homology 3) domain and the putative pore-forming α-helices-5 and -6. These proteins were used to analyse the mechanism of Bax-induced cytochrome c release from mitochondria. None of the Bax proteins caused cytochrome c release merely through physical perturbation of the mitochondrial outer membrane. The α-helices-5 and -6 of Bax were shown to mediate the insertion of the protein into ...
2000) AtBI-1, a plant homologue of Bax Inhibitor-1, suppresses Bax-induced cell death in yeast and is rapidly upregulated during wounding and pathogen challenge. The Plant Journal, 21 (4). pp. 393-399 ...
TY - JOUR. T1 - Adenovirus-mediated bax overexpression for the induction of therapeutic apoptosis in prostate cancer. AU - Li, Xiaoying. AU - Marani, Michela. AU - Yu, Jiang. AU - Nan, Bicheng. AU - Roth, Jack A.. AU - Kagawa, Shunsuke. AU - Fang, Bingliang. AU - Denner, Larry. AU - Marcelli, Marco. PY - 2001/1/1. Y1 - 2001/1/1. N2 - Using adenoviral technology, we overexpressed the proapoptotic molecules pro-caspase-3, pro-caspase-7, and Bax to induce therapeutic apoptosis of prostate cancer cell lines growing in vitro and in vivo. Because overexpressed pro-caspase-3 did not undergo autocatalytic activation in any of the five prostate cancer cell lines evaluated, this strategy was unable to engage any component of the apoptotic pathway. Overexpressed procaspase-7 was proteolytically cleaved in LNCaP and LnCaP-Bcl-2 cells but not in PC-3, DU-145, or TsuPr(1) cells. Cleavage was associated with engagement of many components of the apoptotic pathway, including DEVDase activity, cleavage of ...
The Bcl-2 family member Bax plays a critical role in apoptosis. In healthy resting cells, Bax resides in the cytoplasm and loosely attached to the mitochondrial membrane. Apoptotic stimuli induce Bax activation, which is characterized by translocation and multimerization on the mitochondrial membran …
Etxebarria A., Terrones O., Yamaguchi H., Landajuela A., Landeta O., Antonsson B., Wang H.G., Basanez G.. Endophilin B1/BAX-interacting factor 1 (Bif-1) is a protein that cooperates with dynamin-like protein 1 (DLP1/Drp1) to maintain normal mitochondrial outer membrane (MOM) dynamics in healthy cells and also contributes to BAX-driven MOM permeabilization (MOMP), the irreversible commitment point to cell death for the majority of apoptotic stimuli. However, despite its importance, exactly how Bif-1 fulfils its proapoptotic role is unknown. Here, we demonstrate that the stimulatory effect of Bif-1 on BAX-driven MOMP and on BAX conformational activation observed in intact cells during apoptosis can be recapitulated in a simplified system consisting of purified proteins and MOM-like liposomes. In this reconstituted model system the N-BAR domain of Bif-1 reproduced the stimulatory effect of Bif-1 on functional BAX activation. This process was dependent on physical interaction between Bif-1 N-BAR and ...
A critical hallmark of tumor cell success is evasion of apoptosis. Mcl-1 or Bcl-2. Finally BH3-M6 sensitizes cells to apoptosis induced from the proteasome inhibitor CEP-1612. Bim Poor Bik Bmf Bet Noxa and Puma) (5). Multi-domain pro-apoptotic protein Bax and Bak are definitely necessary for apoptosis (2). In response to mobile tension they induce the discharge from mitochondria of apoptogenic elements such as for example cytochrome as well as the initiation of intrinsic apoptosis. Nevertheless triggered Bax and Bak still could be kept in balance by binding to anti-apoptotic Bcl-2 protein (8 -10). X-ray diffraction and nuclear magnetic resonance (NMR) research have shown how the amphipathic α-helices of pro-apoptotic protein such as for example Bak or Poor BH3 domains match a hydrophobic pocket shaped from the BH1 BH2 and BH3 domains of Bcl-2 Bcl-XL and Mcl-1 (11). When BH3-just protein bind to anti-apoptotic Bcl-2 protein multi-domain protein Bak or Bax become absolve to induce apoptosis (12). ...
In the mouse, the nucleotides three bases downstream of the two response elements are guanine and cytosine, suggesting that dioxin cannot activate Bax. Indeed, mouse oocytes are normally insensitive to dioxin, and oocyte microinjection experiments with a construct containing the wildtype Bax promoter confirm that dioxin is ineffective at induction. Furthermore, mutation of these critical downstream nucleotides to adenine renders the promoter responsive to dioxin. Thus, two nucleotides in the Bax promoter would seem to be the sole protection against damage mediated by dioxin.Matikainen et al.6 further show the effects of the PAH 9,10-dimethylbenz(a)antracene (DMBA) on oocytes and on Bax levels (see figure). Intraperitoneal delivery of DMBA causes a 72% increase in Bax mRNA levels after 24 hours, and a concomitant increase in Bax protein in oocytes. Treatment with DMBA or a DMBA metabolite also leads to a decrease in the number of non-apoptotic oocytes in cultured wildtype mouse ovaries. ...
BTSA1 is a pharmacologically optimized BAX activator that binds with high affinity and specificity to the N-terminal activation site and induces conformational changes to BAX leading to BAX-mediated apoptosis. It effectively promotes apoptosis in leukemia cell lines and patient samples while sparing healthy cells ...
Complete information for BAX gene (Protein Coding), BCL2 Associated X, Apoptosis Regulator, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
Homodimer. Forms higher oligomers under stress conditions. Interacts with BCL2L11. Interaction with BCL2L11 promotes BAX oligomerization and association with mitochondrial membranes, with subsequent release of cytochrome c. Forms heterodimers with BCL2, BCL2L1 isoform Bcl-X(L), BCL2L2, MCL1 and A1. Interacts with SH3GLB1 and HN. Interacts with SFN and YWHAZ; the interaction occurs in the cytoplasm. Under stress conditions, JNK-mediated phosphorylation of SFN and YWHAZ, releases BAX to mitochondria. Isoform Sigma interacts with BCL2A1 and BCL2L1 isoform Bcl-X(L). Interacts with RNF144B, which regulates the ubiquitin-dependent stability of BAX. Interacts with CLU under stress conditions that cause a conformation change leading to BAX oligomerization and association with mitochondria. Does not interact with CLU in unstressed cells. Interacts with FAIM2/LFG2. Interacts with RTL10/BOP. Interacts (via a C-terminal 33 residues) with NOL3 (via CARD domain); inhibits BAX activation and translocation and ...
apoptosis; death receptors; CD95; drugs; resistance; acute myeloid-leukemia; non-hodgkins-lymphoma; apoptosis-inducing ligand; acute lymphoblastic-leukemia; drug-induced apoptosis; cell lung-cancer; nf-kappa-b; bcl-2 antisense oligonucleotide; bax protein expression; flice-inhibitory ...
Immunostaining for Bax/Bcl2 Bax reveals weak expression in the developing decidua, but not in the uterine epithelium of the implantation chamber on 4.5 dpc (a).
Similar experiments were performed with cells from Bak KO mice. In this case, there was somewhat more Bax/106 cells in the heavy membrane fractions from activated T cells than in the fractions from resting T cells, a result we observed intermittently in the activated T cell preparations. The increase in Bax was paralleled by a similar increase in the amount of Tom20 in the heavy membrane fractions, such that the ratio of Bax/Tom20 remained constant within the different types of cells, suggesting that the result is due to an overall increase in the numbers of mitochondria in activated versus resting T cells. In spite of this, the amounts of Bax and Tom20 in the heavy membrane fractions were unaffected by incubation of the activated T cells to bring them closer to death (Fig. 5 B and Fig. S2, which is available at http://www.jem.org/cgi/content/full/jem.20051736/DC1).. These experiments showed that the amount of Bax associated with heavy membranes changes only slightly when cells are activated, ...
Similar to what has been previously observed following treatment of human leukemia cells with SAHA (38, 39, 43), treatment with LAQ824 also induced the hyperacetylation of histones H3 and H4 and increased expression of p21 in SKBR-3 and BT-474 cells. This is due to association of the promoter of p21 with acetylated histones in the nucleosomes (35). In contrast, increase in p27 levels following treatment with HDI is not due to transcriptional up-regulation. It may occur due to a post-transcriptional mechanism (35). Regardless, LAQ824-induced accumulation of p21 and p27 correlated with cytostasis as well as with induction of Bax conformational change, PARP cleavage activity of caspase-3, and apoptosis of SKBR-3 and BT-474 cells. Present studies also demonstrate for the first time that treatment with LAQ824 not only depletes the mRNA levels of Her-2 but also promotes its degradation by the proteasome. The mRNA levels of Her-2/neu declined markedly after short exposure intervals to LAQ824 as ...
Bax兔多克隆抗体(ab53154)可与大鼠, 人样本反应并经WB, ELISA, IHC, ICC/IF实验严格验证,被2篇文献引用并得到1个独立的用户反馈。所有产品均提供质保服务,中国75%以上现货。
Purpose: : In the intrinsic apoptotic pathway, Bcl-2 family member protein Bax triggers cytochrome C release from mitochondria. Thus, it leads to an activation of the downstream caspase cascade ultimately resulting in apoptosis. The aim of the study was to investigate kinetics and up-regulation of this central pro-apoptotic factor in human corneal endothelial cells. Methods: : Human corneal endothelial cells (HCECs, 100% confluence) were incubated with the intrinsic apoptotic inducer Etoposide (a topoisomerase II inhibitor) in increasing concentrations (1.25, 2.5, 5.0 µg/ml). Bax protein level was determined within twelve hours using cell-based ELISA. These results were confirmed by Western blot. The rate of apoptotic HCECs was measured 6h, 12h, 24h and 48h after incubation with Etoposide by flow cytometric assay using Annexin V and Propidium Iodide. Results: : We detected a positive correlation between increasing Bax protein level and apoptotic HCECs. Specifically, HCECs showed an early ...
Bax, a multidomain pro-apoptotic Bcl-2 protein, localizes to the endoplasmic reticulum (ER), where it regulates ER stress-induced apoptosis. Adaptation to ER stress depends on the activation of an integrated signal transduction pathway known as the unfolded protein response (UPR). This study examined the death-inducing activity of Bax and its ability to induce UPR signalling pathways in yeast. We observed that inhibition of global translation in yeast cells expressing Bax correlated with Bax-induced cell death. Using a lacZ reporter containing several UPR cis-activating regulatory elements, we also found that Bax directly activated the UPR. Furthermore, this correlated with the splicing of HAC1 mRNA, a gene involved in UPR activation. Bax induced expression of representative UPR target genes such as KAR2, DER1 and GCN4. Finally, we found that Ire1p function is critical for Bax-induced cell death. Copyright (C) 2012 John Wiley & Sons, Ltd. ...
The proapoptotic BAX protein triggers apoptosis via the intrinsic pathway by inducing mitochondrial outer membrane permeabilization (MOMP). BAX largely exists in an inactive conformation in the cytoplasm, but under cellular stress BAX is activated by BH3-only proteins and translocates to the mitochondrial outer membrane to induce MOMP. Structural studies have revealed conformational changes at the N-terminal surface and C-terminal α9 helix that are required for BAX activation by BH3 proteins and MOMP induction, but suggest that additional mechanisms may stabilize BAX in the inactive cytosolic conformation. Garner, Reyna, and colleagues identified an autoinhibited dimeric BAX conformation in addition to the inactive monomer conformation. The BAX dimers did not induce membrane permeabilization, and, in contrast to BAX monomers, were resistant to BH3-mediated activation. Moreover, BAX dimers failed to translocate to the membrane upon BH3-induced stimulation. Crystallization studies indicated that ...
Mycobacterium tuberculosis (MTB) persists in host macrophages (Mφs) because it has developed mechanisms to escape Mφ killing. In vitro studies have shown that MTB can induce and inhibit apoptosis by causing the expression of Bax and Bcl-2, respectively, suggesting that the infected cells fate depends on pro- and antiapoptotic signals. In the present study, we investigated the role of Bcl-2 in MTB infection in situ. The aim was to study the pattern and distribution of Bcl-2 and Bax in cellular infiltrates of MTB-infected B6D2F1 hybrid mice and correlate the expression with the presence of MTB antigens (MAgs). Using formalin-fixed lung tissues (n = 45), our results showed a significant difference in the percentage of Mφs stained for Bcl-2 or MAgs and Bax (P , 0.0001). Bcl-2 expression was increased in a population of Mφs and corresponded in intensity, colocalization and percentage with that of MAgs on the same cells, while Bax expression was reduced. In lymphocyte aggregates, Bcl-2 and Bax ...
The effects of 20 μg/mL exogenous prostaglandin A2 (PGA2) were determined on Bax, Bcl-2 and proliferating cell nuclear antigen (PCNA) expression levels in MCF-7 cells. Flow cytometric analysis indicated a pronounced increase in the S phase and a decrease in the G1 phase, whereas a significant increase in the DNA content preceding the G0/G1 peak was also observed after 48 h of exposure to PGA2. Confirmation of apoptosis was determined after 12 h, 36 h and 48 h of PGA2 exposure employing the mitosensor reagent that detects potential changes in the mitochondrial membrane. Twenty-eight percent of PGA2-exposed cells were in apoptosis when compared to the 7.1% vehicle-treated cells after 48 h. PGA2 exposure led to statistically significant increase (1.25-fold) over vehicle-treated controls in Bax expression levels. Decreases in Bcl-2 (0.79-fold), as well as PCNA (0.69-fold) expression levels over vehicle-treated controls were observed. The Bax/Bcl-2 ratio for PGA2-exposed cells was 2.7. The present ...
Going further and looking more carefully at the intracellular kinetics of CCR, we observed that what we described so far as a coordinated and `all-or-none phenomenon seemed in fact to be polarized, and to spread or propagate within cells (Fig. 3D,E). For instance, in the cell of Fig. 3D, CCR clearly initiated in the mitochondria populating the left cell extremity, and progressively propagated up to the mitochondria located in the extreme right zone of the cytoplasm. CCR recorded at the level of small individual groups of mitochondria positioned along the cell axis exhibited constant internal kinetics, but was triggered gradually, suggestive of a traveling wave of CCR (Fig. 3E). This phenomenon preceded Bax motion - evidenced either by computing the standard deviation of pixel intensity (Goldstein et al., 2000) (Fig. 3D, right plot) or by direct intensity measurement within mitochondrial regions of interest (not shown) - was not distinctive of CCR induced by STS and was also observed after FasL ...
We have identified a new pro-apoptotic Bcl-2-related protein Bok, based on its binding to an ovarian anti-apoptosis protein Mcl-1. In addition to its restricted expression in several reproductive tissues, Bok also shows a selective heterodimerization property by interacting with some (Mcl-1, BHRF1, and Bfl-1) but not other (Bcl-2, Bcl-xL, and Bcl-w) anti-apoptotic proteins. Coupled with findings showing that Bok-induced apoptosis could only be antagonized by selective anti-apoptotic proteins, the present data suggest that different pro- and anti-apoptotic Bcl-2 protein pairs may play tissue-specific roles in the regulation of apoptosis. Because of the restricted expression of Bok to ovarian granulosa cells and several reproductive tissues characterized by hormonally regulated cyclic cell turnover, further analyses of Bok action in the gonads and uterus could provide unique models to study the hormonal regulation of apoptosis. Because most of the Bcl-2-related proteins have been identified in the ...
Functional interaction of Bcl-2/Bcl-xL and Bax/Bak, but not Bid/Bik, with the VDAC. Bax/Bak directly opens the VDAC to induce cytochrome c release, while Bcl-2/
Critical issues in apoptosis include the importance of caspases versus organelle dysfunction, dominance of anti- versus proapoptotic BCL-2 members, and whether commitment occurs upstream or downstream of mitochondria. Here, we show cells deficient for the downstream effectors Apaf-1, Caspase-9, or C …
Chen M., Huang L., Shabier Z., Wang J.. The lifespan of dendritic cells (DCs) can potentially influence immune responses by affecting the duration of DCs in stimulating lymphocytes. Significant differences in the lifespan have been reported for various DC subsets, however, the molecular mechanisms for regulating such differences between DC subsets remain unclear. In this study, we compared the apoptosis signaling molecules in two major DC subjects, the myeloid DCs (mDCs) and plasmacytoid DCs (pDCs). We observed a lower ratio between anti-apoptotic Bcl-2/Bcl-xL and pro-apoptotic Bax/Bak in shorter-lived myeloid DCs (mDCs) than in longer-lived plasmacytoid DCs (pDCs) or T cells. Transfection with Bcl-2 or Bcl-xL prolonged the survival of mouse primary mDCs in vitro, while deletion of Bcl-2 accelerated DC turnover in vivo. In addition, the ratios between anti-apoptotic Bcl-2/Bcl-xL and pro-apoptotic Bax/Bak could be regulated in DCs. Signaling from toll-like receptors (TLRs) up-regulated Bcl-xL and ...
BTSA1 is a pharmacologically optimized BAX activator that binds with high affinity and specificity to the N-terminal activation site and induces conformational changes to BAX leading to BAX-mediated apoptosis. It effectively promotes apoptosis in leukemia cell lines and patient samples while sparing healthy cells. Buy Bcl-2 inhibitor BTSA1 from AbMole BioScience.
Overexpression of the prosurvival Bcl-2 family members (Bcl-2, Bcl-xL, and Mcl-1) is commonly associated with tumor maintenance, progression, and chemoresistance. We previously reported the discovery of ABT-737, a potent, small-molecule Bcl-2 family protein inhibitor. A major limitation of ABT-737 is that it is not orally bioavailable, which would limit chronic single agent therapy and flexibility to dose in combination regimens. Here we report the biological properties of ABT-263, a potent, orally bioavailable Bad-like BH3 mimetic (K(i)s of |1 nmol/L for Bcl-2, Bcl-xL, and Bcl-w). The oral bioavailability of ABT-263 in preclinical animal models is 20% to 50%, depending on formulation. ABT-263 disrupts Bcl-2/Bcl-xL interactions with pro-death proteins (e.g., Bim), leading to the initiation of apoptosis within 2 hours posttreatment. In human tumor cells, ABT-263 induces Bax translocation, cytochrome c release, and subsequent apoptosis. Oral administration of ABT-263 alone induces complete tumor
摘要(Abstract): 目的观察大鼠局灶性脑缺血再灌注(ischemiareperfusion,I/R)损伤后海马CA1区神经元凋亡、TUNEL阳性细胞变化,以及凋亡相关蛋白Bcl-2与Bax蛋白的表达情况。方法将健康雄性SD(Sprague-Dawley)大鼠随机分为假手术组和I/R组,每组再分为缺血再灌注后3、6、12、24、48、72 h亚组。应用免疫组化方法检测再灌注后不同时间点大鼠海马CA1区神经元凋亡基因Bcl-2和Bax蛋白的表达及Bcl-2/Bax比值变化,采用原位细胞凋亡检测(TUNEL)技术检测凋亡阳性细胞数。结果各组非缺血侧相应区域神经元胞质中Bcl 2均有微弱表达。I/R组缺血侧海马CA1区于再灌注3 h开始出现Bcl-2和Bax蛋白微弱表达,随再灌注时间延长神经元内Bcl-2表达逐渐增强,再灌注24 h后Bcl-2表达达高峰,假手术组与I/R组比较差异有统计学意义( ...
Notwithstanding this classification program has permitted significant advances in cancer treatment, it is actually not always accurate. To date, many efforts happen to be targeted to the dis covery of new biomarkers revealing the biological profile recommended reading of each NPC case, consequently contributing to NPC diag nosis and prognosis, at the same time as to prediction of successful therapeutic tactics and monitoring of patients re sponse to treatment method. A few possible NPC biomarkers have already been studied, such as molecules implicated in pathways affecting major cellular properties, this kind of as cell proliferation, apoptosis, invasion, and metastasis. Hardly ever theless, no established tissue molecular markers for NPC are implemented to date in clinical practice, hence, the iden tification of novel prognostic and predictive biomarkers for NPC is often a high necessity. The aforementioned information prompted us to analyze BAX mRNA expression in 88 malignant and 9 ...
The Bcl-2 gene family encodes a set of proteins involved in apoptotic inhibition, which are commonly analyzed during the performance of a Bcl-2 apoptosis assay. The ApoPrimer Set (Bcl-2 family) for RT-PCR is composed of a set of primers used to amplify cDNA derived from the mRNA of 7 Bcl-2 family (mcl-1, bfl-1, bax-alpha, bcl-2, bak, bik, bcl-x) members as well as a beta-actin control. A positive control RNA is also included. The beta-actin primer is a useful internal control for sample quantification and for comparison between samples. PCR products generated from the positive control RNA can be distinguished from target mRNA due to size differences of the amplified products. ...
The Bcl-2 gene family encodes a set of proteins involved in apoptotic inhibition, which are commonly analyzed during the performance of a Bcl-2 apoptosis assay. The ApoPrimer Set (Bcl-2 family) for RT-PCR is composed of a set of primers used to amplify cDNA derived from the mRNA of 7 Bcl-2 family (mcl-1, bfl-1, bax-alpha, bcl-2, bak, bik, bcl-x) members as well as a beta-actin control. A positive control RNA is also included. The beta-actin primer is a useful internal control for sample quantification and for comparison between samples. PCR products generated from the positive control RNA can be distinguished from target mRNA due to size differences of the amplified products. ...
There is an increasing body of evidence demonstrating the implication of apoptosis and/or its regulating proteins in the outcome of tumors treated by RT and chemotherapy (7 , 21, 22, 23, 24, 25) . In the present study, we investigated the value of the expression of the proapoptotic proteins Bax and p53 and of the antiapoptotic proteins Bcl-2 and Mcl-1, as well as the value of spontaneous apoptosis regarding the outcome in patients who have had nonsurgical treatment for anal cancer. With the exception of p53, to our knowledge, this is the first study that addresses the question of prognostic significance of these proteins in this disease. Although rare, anal carcinoma is one of the few cancers treated primarily by RT and chemotherapy. Identification of factors that can reliably predict a favorable treatment outcome would, thus, have paramount clinical importance in this disease. Moreover, biological predictive factors shown to be reliable in anal carcinoma might prove to be of value in other ...
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Inhibition of apoptotic Bax translocation to the mitochondria is a central function of parkin. Cell Death Dis. 2014 Jul 03; 5:e1313 ...
Rabbit polyclonal antibody raised against a synthetic peptide of BAX. A synthetic peptide (conjugated with KLH) corresponding to N-terminus of human BAX. (PAB0810) - Products - Abnova
Human BAX full-length ORF ( AAH14175, 1 a.a. - 192 a.a.) recombinant protein with GST-tag at N-terminal. (H00000581-P01) - Products - Abnova
YC-137 is a BCL-2 inhibitor, which selectively induces apoptosis of Bcl-2-overexpressing cells and disrupts its interaction with Bid BH3, thereby blocking the anti-apoptotic activity of Bcl-2.
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Supplementary MaterialsFigure 1source data 1: Resource data indicating that BimL requires a CTS to induce MOMP in HEK293 cells. to membranes. elife-44525-fig4-data1.xlsx (18K) GUID:?6217D04D-BD0F-4FF4-97F3-EA7D1AC332EC Figure 5source data 1: Source data demonstrating that recombinant BimL-dCTS indirectly activates Bax through inhibition of Bcl_XL. elife-44525-fig5-data1.xlsx (15K) GUID:?2FBDE8FA-CD3F-4B89-86F2-CB6EDE9F5481 Figure 6figure supplement 1source data 1: Source data with fitted curves used to calculate dissociation constants Ntn1 and EC50s for Figure 6B. elife-44525-fig6-figsupp1-data1.xlsx (52K) GUID:?39E7B383-B55E-415D-BD93-37BD0557E842 Figure 7source data 1: Source data demonstrating that BimL-dCTS-MAO binds to liposomes and Bax, but activates Bax poorly. elife-44525-fig7-data1.xlsx (18K) GUID:?47A95C70-2208-4738-8FA6-F19BF88AA00F Figure 7figure supplement 1source data 1: Source data demonstrating BimL-dCTS-MAO binds to mitochondria but binds poorly to Bax. ...
The Pa-PDT induced p-JNK caused down-regulation of the pro-apoptotic protein bcl-2 that facilitates the collapse of mitochondrial membrane and eventually initiates the intrinsic apoptotic pathway ...
overexpressing GPX1 in endothelial cells is able to change the basal mRNA and protein BAX levels without affecting those of TP53 and BCL2 (useful to antiatherogenic therapies which use antioxidants with the aim of protecting the vascular wall against ...
摘要(Abstract): 目的探讨孕期不同剂量苯并(a)芘暴露对仔鼠肝脏凋亡相关蛋白Bcl-xl和Bax表达水平的影响。方法将雌雄大鼠合笼后雌性SD大鼠见阴栓确定为受孕,以检出日为孕期第0 d。将孕鼠随机分为4组,每组8只,分为对照组(玉米油)和苯并(a)芘处理组(0.75 mg/kg、1.5 mg/kg和3 mg/kg)。从妊娠第3 d开始经灌胃苯并(a)芘直到妊娠第17 d结束,分别在孕0、4、7、14、19 d称孕鼠体重。待其自然分娩后24 h内测量仔鼠的体重、身长及尾长,然后取仔鼠肝脏,采用Western blot方法检测仔鼠肝脏中Bcl-xl和Bax蛋白的表达水平。结果随着孕期苯并(a)芘暴露水平的增加,新生仔鼠体重、身长、尾长等生长发育指标均有一定程度的下降,但未达到显著性差异(P>0.05)。Western blot结果显示,与对照组相比,中、高剂量染毒组仔鼠肝脏的Bcl-xl蛋白表达均明显下降,Bax蛋白表达均明显升高,差异均有统计学意义( ...
Venetoclax (ABT-199, GDC-0199)是一种Bcl-2选择性抑制剂,无细胞试验中Ki为
The Bcl-2 family of proteins is characterized by its ability to modulate cell death (apoptosis) under a broad range of physiological conditions.…
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Recommended Review Article:. Chipuk JE, Green DR. 2008. How do BCL-2 proteins induce mitochondrial outer membrane permeabilization? TRENDS IN CELL BIOLOGY 18(4): 157-164. Recommended Articles:. Aslan JE, Thomas G. 2009. Death by Committee: Organellar Trafficking and Communication in Apoptosis. TRAFFIC 10(10): 1390-1404. Chipuk JE, Green DR. 2009. PUMA cooperates with direct activator proteins to promote mitochondrial outer membrane permeabilization and apoptosis. CELL CYCLE 8(17): 2692-2696. Chipuk JE, Bouchier-Hayes L, Green DR. 2006. Mitochondrial outer membrane permeabilization during apoptosis: the innocent bystander scenario. CELL DEATH AND DIFFERENTIATION 13(8): 1396-1402 Chipuk JE, Green DR. 2006. Dissecting p53-dependent apoptosis. CELL DEATH AND DIFFERENTIATION 13(6): 994-1002 Chipuk JE, Bouchier-Hayes L, Kuwana T, et al. 2005. PUMA couples the nuclear and cytoplasmic proapoptotic function of p53 . SCIENCE 309(5741): 1732-1735. Kuwana T, Bouchier-Hayes L, Chipuk JE, et al. 2005. BH3 ...
23284 Comment by Andrea LeBlanc: This interesting paper shows that quite a few of the disease-associated human prion mutations actually switch to the normal Doppel sequence. The doppel (i.e., doppelgaenger) gene is downstream of the PrP gene. Its protein resembles amino-terminally truncated PrP and interacts with PrP.) Doppel overexpression is neurotoxic. Therefore, the switch of PrP into a Doppel-like protein could indicate that Doppel and mutant PrP are neurotoxic through a similar mechanism. However, it remains to be seen if these mutant PrPs are neurotoxic or not.. Our work has focused on the function of normal prion protein in primary human neurons. I suspected a function for prion protein in cell death or cell survival because of some similarity between the BH2 domain of Bcl-2 proteins and the octapeptide repeat of prion protein. While we now know that PrP is not a member of the Bcl-2 family of proteins, it is, however, a strong neuroprotective agent against Bax-mediated cell death. We ...
TY - JOUR. T1 - Increased cardiomyocyte apoptosis and changes in proapoptotic and antiapoptotic genes bax and bcl-2 during left ventricular adaptations to chronic pressure overload in the rat. AU - Condorelli, Gianluigi. AU - Morisco, Carmine. AU - Stassi, Giorgio. AU - Notte, Antonella. AU - Farina, Felicia. AU - Sgaramella, Giuseppe. AU - De Rienzo, Assunta. AU - Roncarati, Roberta. AU - Trimarco, Bruno. AU - Lembo, Giuseppe. PY - 1999/6/15. Y1 - 1999/6/15. N2 - Background - Left ventricular hypertrophy (LVH) represents both an adaptive response to increased cardiac work load and a precursor state of heart failure. Recent evidence linked cardiac myocyte death by apoptosis with LVH and heart failure. It remained unclear, however, whether apoptosis participated in the transition from LVH to left ventricular dysfunction (LVD). Methods and Results - Cardiac myocyte apoptotic events and changes in apoptosis-specific genes were studied in a rat model of chronic pressure overload induced by ...
The Bcl-2 family of proteins regulates mitochondrial outer membrane permeabilization (MOMP) - considered as the point-of-no-return in apoptosis. As the gatekeeper for survival or death of cells, this network is tightly regulated by interactions of its members with opposing functions. The embedded together model remains as one of the most accepted models to describe the interactions between family members. This model highlights the role of the mitochondrial membrane to augment these interactions. And while this model has been repeatedly exemplified in vitro, the e↵ect of membranes on Bcl-2 protein interactions has not yet been fully explored in living cells. On the other hand, the Bcl-2 proteins could also a↵ect the physical properties of the membrane. Bax and Bak are the main e↵ectors of apoptosis, believed to form pores on the mitochondrial outer membrane. However, no one has seen an apoptotic pore. Aside from its permeabilizing activity, the e↵ect of Bcl-2 proteins on the physical ...
Title: Bcl-2 Proteins: Targets and Tools for Chemosensitisation of Tumor Cells. VOLUME: 3 ISSUE: 4. Author(s):Ali Bettaieb, Laurence Dubrez-Daloz, Sophie Launay, Stephanie Plenchette, Cedric Rebe, Severine Cathelin and Eric Solary. Affiliation:INSERM U517, IFR 100, 7 boulevard Jeanne dArc, 21000 Dijon, France.. Keywords:apoptosis, cell death, bcl-2, bh3-only proteins, mitochondria, antisense oligonucleotides, bh3 mimetics. Abstract: Proteins of the Bcl-2 family share one or several Bcl-2 homology (BH) regions and behave as pro- or antiapoptotic proteins. Prosurvival members such as Bcl-2 and Bcl-XL are supposed to preserve mitochondrial outer membrane integrity, thus preventing the release of soluble apoptogenic molecules. Pro-apoptotic members include BH3- only proteins that act as sensors of cellular damage and initiate the death process and Bax-like proteins that act downstream of BH3-only proteins to permeabilise the mitochondrial outer membrane. Whether BH3-only proteins directly activate ...
The findings reported here demonstrate that BMS-247550 (EpoB), a lactam analogue of epothilone B, kills cells through a mitochondrial pathway of apoptosis controlled by Bcl-2 and Bax. Similar to Taxol, EpoB causes cell cycle arrest at the G2-M transition and secondarily induces apoptosis of human breast cancer cells. In agreement with this, cells synchronized in G2-M phase of the cell cycle are more sensitive to EpoB-induced cytotoxicity. Upon EpoB treatment, Bax undergoes a conformational change and subsequently translocates to mitochondria. This conformational change of Bax occurs upstream of Bid cleavage, cytochrome c release, and caspase activation. In addition, overexpression of Bcl-2 decreases EpoB-induced Bax conformational change, cytochrome c release, and apoptosis, whereas blockade of Bcl-2 by Bak-BH3 peptide or HA14-1 increases EpoB-mediated cytotoxicity.. In healthy cells, Bax exists predominantly in the cytosol, despite the presence of a typical membrane-anchoring sequence near its ...
The P4 position of caspase cleavage sites confers protease specificity (10). Consistent with the preference for Asp at the P4 position of caspase-3 cleavage sites, mutation of Asp31 (D31A) also abolished cleavage of Bcl-2 by caspase-3 in vitro (11). However, Asp31 itself apparently does not serve as a cleavage site because this site is preserved in the loop deletion mutant Δloop, which is not cleaved. (Deletion of the loop region reconstitutes Ala32.) The Asp residues at P1 and P4 in human Bcl-2 are also conserved in the rat and murine Bcl-2 proteins.. To determine whether Bcl-2 is cleaved inside cells, we cotransfected COS cells with plasmids expressing Bcl-2 and caspase-3. Approximately 50% of the Bcl-2 protein was cleaved in the presence of caspase-3 (Fig. 1B). Similar to results obtained in vitro, mutation of Asp31 or Asp34 abolished proteolysis in transfected cells, whereas mutation of Asp64 had no effect. Cotransfection of the baculovirus caspase inhibitor P35 abolished proteolysis of ...
The P4 position of caspase cleavage sites confers protease specificity (10). Consistent with the preference for Asp at the P4 position of caspase-3 cleavage sites, mutation of Asp31 (D31A) also abolished cleavage of Bcl-2 by caspase-3 in vitro (11). However, Asp31 itself apparently does not serve as a cleavage site because this site is preserved in the loop deletion mutant Δloop, which is not cleaved. (Deletion of the loop region reconstitutes Ala32.) The Asp residues at P1 and P4 in human Bcl-2 are also conserved in the rat and murine Bcl-2 proteins.. To determine whether Bcl-2 is cleaved inside cells, we cotransfected COS cells with plasmids expressing Bcl-2 and caspase-3. Approximately 50% of the Bcl-2 protein was cleaved in the presence of caspase-3 (Fig. 1B). Similar to results obtained in vitro, mutation of Asp31 or Asp34 abolished proteolysis in transfected cells, whereas mutation of Asp64 had no effect. Cotransfection of the baculovirus caspase inhibitor P35 abolished proteolysis of ...
BackgroundThe Bcl-2-associated X protein (Bax) is a proapoptotic member of the Bcl-2 family known to be activated and upregulated during apoptosis. Single nucleotide polymorphisms (SNPs) in Bax promoter may participate in the process of carcinogenesis by altering its own expression and the cancer related genes. Bax-248G|A polymorphism has been implicated to alter the risk of cancer, but the listed results are inconsistent and inconclusive. In the present study, we performed a meta-analysis to systematically summarize the possible association of this polymorphism with the risk of cancer. MethodologyWe conducted a search of case-control studies on the associations of Bax-248G|A polymorphism with susceptibility to cancer in Pub Med, Science Direct, Wiley Online Library and hand search. Data from all eligible studies based on some key search terms, inclusion and exclusion criteria were extracted for this meta-analysis. Hardy-Weinberg equilibrium (HWE) in controls, power calculation, heterogeneity analysis
The BCL-2 family of proteins forms a complex interaction network that regulates cellular life and death decisions and contributes to cancer development, maintenance, and chemoresistance. BH3 only member proteins (e.g. BIM) serve as cellular stress sentinels and, when triggered, signal irreversible activation of apoptosis through their α-helical BH3 death domains. These pro-apoptotic signals are normally held in check by the multidomain anti-apoptotic proteins (e.g. BCL-XL, MCL-1) but when they are unable to do so the multidomain pro-apoptotic proteins BAX and BAK induce cell death through pore formation in the mitochondrial outer membrane. Therapeutic manipulation of the BCL-2 family with BH3 mimetics (including small molecules and synthetic peptides) is an emerging paradigm in cancer treatment and immune modulation. The design of next-generation therapeutics based on the BIM BH3 helix offers the unique advantage of recapitulating BIMs natural capacity to directly target the full complement of ...
Colorectal cancer is one of the most common causes to death due to cancer in the world. It is important to understand the molecular mechanisms behind tumour development for both prognostic and therapeutic applications. In this thesis, we have focused on genes and proteins related to tumour suppressor function, apoptosis and DNA repair in patients with colorectal adenocarcinomas. In Paper I, the pattern of mutations affecting the tumour suppressor p53 was investigated in 75 cases in order to determine whether there were any specific mutations in the cases with p53 accumulated in the cytoplasm. We found that the frequency and pattern of mutation were similar to those with nuclear p53 expression, suggesting that the prognostic importance of cytoplasmic p53 accumulation may depend on both mutational and non-mutational mechanisms. In Paper II we investigated the protein expression of the pro-apoptotic gene Bax from normal mucosa to primary tumour and to regional lymph node metastases in 135 patients. ...
Tissue destruction that occurs upon infection with the bacterium Escherichia coli 0157:H17 is attributed in part to the bacterial factor verotoxin II (VTII), but the molecular mechanism of cell-death induction has not been clear. Suzuki et al. report that VTII has a pentameric sequence that is identical to a sequence found in the BH1 domain of mitochondrial Bcl-2, a protein that inhibits apoptosis. The BH1 domain of Bcl-2 mediates interaction with other Bcl-2 family members to suppress cell death. Biochemical analysis indicates that the pentameric sequence of VTII interacts with Bcl-2. When cells expressing Bcl-2 were treated with VTII, caspase 3 activation and subsequent apoptosis occurred. VTII also localized to mitochondria where Bcl-2 resides. The authors propose that VTII-Bcl-2 interaction is one of the death-induction mechanisms utilized by this bacterium. However, the molecular mechanism by which VTII induces cell death through Bcl-2 remains to be determined, but may involve blocking of ...
TY - JOUR. T1 - The Bax inhibitor UvBI-1, a negative regulator of mycelial growth and conidiation, mediates stress response and is critical for pathogenicity of the rice false smut fungus Ustilaginoidea virens. AU - Xie, Songlin. AU - Wang, Yufu. AU - Wei, Wei. AU - Li, Chongyang. AU - Liu, Yi. AU - Qu, Jinsong. AU - Meng, Qianghong. AU - Lin, Yang. AU - Yin, Weixiao. AU - Yang, Yinong. AU - Luo, Chaoxi. PY - 2019/10/1. Y1 - 2019/10/1. N2 - Bax inhibitor-1 (BI-1), an evolutionarily conserved protein, is a suppressor of cell death induced by the proapoptotic protein Bax and is involved in the response to biotic and abiotic stress in animals, plants and yeast. Rice false smut caused by Ustilaginoidea virens is one of the destructive rice diseases worldwide. Although BI-1 proteins are widely distributed across filamentous fungi, few of them are functionally characterized. In this study, we identified a BI-1 protein in U. virens, UvBI-1, which contains a predicted Bax inhibitor-1-like family domain ...
Opening track Done Me Wrong unfurls perfectly, with all the hallmarks of classic.. . Bax. Mosca; Release Date ; Label Numbers; Catalog NMBRS16 Done Me Wrong Original Mix Bax Original Mix Aus Music. Ever since Mosca crashed into the electronic-music world in early One: hes not particularly prolific, as Done Me Wrong b/w Bax is. Buy Done Me Wrong/Bax (12) by Mosca (12 $). Amoeba Music. Ships Free in the U.S. View credits, reviews, tracks and shop for the Vinyl release of Done Me Wrong / Bax on Discogs. Mosca - Done Me Wrong Bax, on the other hand, not so much. is just a little intro to the music I make, the trax I run, and a bit about me. Done Me Wrong / Bax, a Single by Mosca. Released 19 September on Numbers. (catalog no. NMBRS16; Vinyl 12). Genres: Speed Garage. Opening track Done Me Wrong unfurls perfectly, with all the hallmarks of classic.. . Bax. Mosca; Release Date ; Label Numbers; Catalog NMBRS16 Done Me Wrong Original Mix Bax Original Mix Aus Music. Ever since Mosca crashed ...
TY - JOUR. T1 - Effects of aging on expression of genes involved in regulation of proliferation and apoptosis in the colonic epithelium. AU - Lee, Heung Man. AU - Greeley, George H.. AU - Englander, Ella W.. N1 - Funding Information: Supported by a grant from the National Institutes of Health (PO1 DK35608). PY - 2000/6/20. Y1 - 2000/6/20. N2 - The purpose of this study was to characterize the effects of aging on colonic messenger ribonucleic acid (mRNA) and protein levels of genes involved in the regulation of cell proliferation and apoptosis, and epithelial morphology in male Fischer 344 rats. Our study shows that, with aging, colonic expression of insulin-like growth factor-1 (IGF-1) and IGF-binding protein-3 (IGFBP-3) is significantly increased and decreased, respectively. Colonic Bax protein levels are increased significantly with aging. Immunohistochemical localization of Bax protein shows a greatly increased expression in colonic crypts, especially in the upper portion of crypts. p53 ...
Venetoclax, also known as ABT-199 or GDC0199, is an orally bioavailable, selective small molecule inhibitor of the anti-apoptotic protein Bcl-2, with potential antineoplastic activity. Venetoclax mimics BH3-only proteins, the native ligands of Bcl-2 and apoptosis activators, by binding to the hydrophobic groove of Bcl-2 proteins thereby repressing Bcl-2 activity and restoring apoptotic processes in tumor cells.
To determine whether resveratrol, a natural plant-derived drug, has protective effects against antibody-induced apoptosis of retinal cells in vitro and to provide insights on the mechanism of resveratrol protection. E1A.NR3 retinal cells pretreated with 40 μM resveratrol were grown in the presence of anti-recoverin (Rec-1), anti-enolase (Enol-1) antibodies, and normal purified immunoglobulins. When the cells were exposed to resveratrol before treatment with Enol-1 or Rec-1 antibodies, 30-55% more cells survived compared to the resveratrol-untreated cells. Western blotting showed a reduction in proapoptotic protein Bax in the cytoplasm and mitochondria of resveratrol-treated cells. Resveratrol-pretreated cells also showed a significant decrease in intracellular calcium and an inhibition of caspase-3 activity as compared to the untreated cells. Sirt1 expression was greatly reduced in the cells grown in the presence of Rec-1 and Enol-1, but it increased about five times in the resveratrol-pretreated cells
The power of interferons (IFNs) to inhibit viral replication and cellular proliferation is well established but the specific contribution of each IFN-stimulated gene (ISG) to these biological responses remains to be completely understood. In addition ISG54 was not able to promote cell death in the absence of pro-apoptotic Bcl family members Bax and Bak. Analyses of binding partners of ISG54 uncovered association with two homologous protein ISG56/IFIT1 and ISG60/IFIT3. Furthermore ISG60 binding regulates the apoptotic ramifications of GDC-0973 ISG54 negatively. The outcomes reveal a previously unidentified function of ISG54 in the induction of apoptosis with a mitochondrial pathway and shed brand-new light over the mechanism where IFN elicits anti-viral and anti-cancer results. (6). Still a primary hyperlink of ISGs to mitochondrial-mediated cell loss of life continues to be to become characterized. Within this survey we recognize ISG54 being a GDC-0973 mediator of mitochondrial cell loss of ...
Supplementary Materialsoncotarget-10-6219-s001. domains. BH3-only proteins can straight bind and activate BAX/BAK or can put their amphipathic BH3 -helix right into a groove on anti-apoptotic proteins target(s) leading to release and following indirect BAX/BAK activation [1]. Cancers cells have always been recognized to evade cell loss of life through overexpression of anti-apoptotic BCL-2 associates or through down-regulation of BH3-just proteins [1]. To get over these hurdles theres a great pharmacologic crusade to build up agents that straight engage BCL-2 family members proteins to induce loss of life whatever the cells origins or hereditary perturbations [2]. Despite early guarantee, many BH3-mimetics, never have translated towards the medical clinic or have already been which can function successfully, at least partly, in addition to the BCL-2 network [3C5]. Functional redundancy inside the BCL-2 family members makes it complicated to tailor effective healing strategies without incurring ...
Supplementary MaterialsS1 Fig: The Jejunal mucosal morphology from the weaned pigs. probiotic stress. The purpose of this research was to research whether nutritional LGG supplementation could relieve diarrhea via enhancing jejunal mucosal hurdle function in the weaned piglets challenged by RV, and additional analyze the tasks for apoptosis of jejunal mucosal cells and intestinal microbiota. A complete of 24 crossbred barrows weaned at 21 d old had been assigned randomly to at least one 1 of 2 diet programs: the basal diet plan and LGG supplementing diet plan. On day time 11, all pigs had been orally infused RV or the sterile essential medium. RV infusion increased the diarrhea rate, increased the RV-Ab, NSP4 and IL-2 buy lorcaserin HCl concentrations and the Bax mRNA levels of jejunal mucosa (GG (LGG), isolated by Glodin and Gorbach from the healthy adults faece [5C6], has been shown some probiotic characteristics, including high adhesion capacity GG, a generous gift from Professor Shiyan Qiao ...
Korhonen, L., Belluardo, N., Mudo, G. and Lindholm, D. (2003), Increase in Bcl-2 phosphorylation and reduced levels of BH3-only Bcl-2 family proteins in kainic acid-mediated neuronal death in the rat brain. European Journal of Neuroscience, 18: 1121-1134. doi: 10.1046/j.1460-9568.2003.02826.x ...
Programmed cell death. Neurons are programmed to die in great numbers during normal human development and aberrantly die by apoptosis in several neurodegenerative disorders. We are exploring the molecular mechanism of apoptosis concentrating on the roles of mitochondria and the Bcl-2 family of proteins. We have found that Bcl-xL and Bax move from the cytosol compartment to the mitochondria during apoptosis and that this step critically commits cells to the death pathway. Two major aspects of this process are under investigation; the molecular trigger for Bax migration into mitochondria and the consequences of Bax insertion into mitochondria. Live cell imaging of mitochondria and Bcl-2 family members analyzed by confocal microscopy has been instrumental in recent studies that link mitochondrial division processes to Bax mediated apoptosis. Unexpectedly, Bcl-2 family proteins have been found to regulate mitochondrial morphogenesis in healthy cells leading us to actively study the roles of ...
With ActivStyles personalized service, you can spend more time caring for your loved one and less time worrying about their medical supplies. ActivStyle is here to provide an easy way to collar the home medical supplies you call, when you requisite them. We pay over 30 jillion dollars pa on dieting products purchase gyne-lotrimin 100mg fast delivery antifungal drink. While the 5-year survival of the patients in the chemoradiation arm was 62 % and the sur- vival toll was 58 % in the emission unattended arm, this difference failed to reach statistical significance. The Bcl-2 kinsfolk proteins can be divided into three significant subgroups: (1) Anti-apoptotic proteins, such as Bcl-2, Bcl-XL, and Mcl-1, which typically interest four conserved motifs termed Bcl-2 homology (BH) domains and can species heterodimers with Bax, inhibiting mitochondrial cytochrome c release and protecting against chamber destruction; (2) The pro-apoptotic proteins, such as Bax, Bak, and Bok, which typically entertain ...
PMCID: PMC3863416. 2012. Buttermore ED, Piochon C. Wallace M, Philpot B, Hansel C, Bhat MA. 2012. Pinceau organization in the cerebellum requires distinct functions of Neurofascin in Purkinje and basket neurons during postnatal development. J Neurosci. 32(14), pp. 4724-4742.. Chen YC, Lin YQ, Banerjee S, Venken K, Li J, Ismat A, Chen K, Duraine L, Bellen HJ, Bhat MA. 2012. Drosophila Neuroligin 2 is required presynaptically and postsynaptically for proper synaptic differentiation and synaptic transmission. J. Neurosci. 32(45), pp. 16018-30.. Coutinho-Budd J, Ghukasyan V, Zylka MJ, and Polleux F. 2012. The F-BAR domains from srGAP1, srGAP2, and srGAP3 differentially regulate membrane deformation. J. Cell Sci. 125(14), pp. 3390-401.. Dumitru, R, Gama, V, Fagan, M, Bower, J, Pevny, L, and Deshmukh, M. 2012. Human embryonic stem cells have constitutively active bax at the golgi and are primed to undergo rapid apoptosis. Mol. Cell. 5, pp. 573-83. Higginbotham H, Eom TY, Mariani LE, Bachleda A, Hirt ...
BCL-2: …in mammals known as the BCL-2 protein family. This protein family, which provides the framework for controlling apoptosis, takes its name from a type of cancer called B-cell lymphoma. BCL-2, the first family member, forms the molecular basis for sustaining the lymphoma cancer cells. The BCL-2 family of proteins has…
An alternative essential proapoptotic protein, BAK, was not upregulated by lethal UVB doses in either early or late passage cells . BAK, in contrast to BAX, is not really acknowledged to be a transcriptional target of P. We then examined anti apoptotic proteins. BCL was downregulated by UVB in both early and late passage cells at h submit irradiation . No visible distinction was observed among passage amounts. The scenario was quite different for BCL xL. As expected , BCL xL was quickly downregulated in youthful fibroblasts starting at h publish UVB. Strikingly, the basal BCL xL degree in outdated fibroblasts was instead rapidly upregulated following UVB and reached a plateau at h . BCLxL acts by antagonistically binding to pro apoptotic partners such as BAX. We for this reason quantitated the adjust in BAX BCL xL ratio among very low and high passage ranges . In youthful cells , this ratio increased fold h right after UVB however it was unchanged during the old cells . This end result displays ...
Principal Investigator:MORIKAWA Keiko, Project Period (FY):1994 - 1995, Research Category:Grant-in-Aid for General Scientific Research (C), Research Field:Hematology
In an upcoming G&D paper, Dr. Albert Baldwin and colleagues (UNC School of Medicine) lend new insight into an alternate mechanism of p53 inactivation in tumor cells. The researchers found that the putative oncoprotein Bcl-3, which is expressed in some leukemias and solid tumors, potently suppresses p53 activation through a mechanism that involves the controlled upregulation of Hdm2 gene expression. ...
The present invention provides novel anticode oligomers and methods of using them for controlling the growth of cancer cells expressing the bcl-2 gene.
The present invention provides novel anticode oligomers and methods of using them for controlling the growth of cancer cells expressing the bcl-2 gene.
BAK1 belongs to the BCL2 protein family. BCL2 family members form oligomers or heterodimers and act as anti- or pro-apoptotic regulators that are…
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Such proteins include Bcl-2 and Bax. Bcl-2 is an antiapoptotic protein. The level of Bcl-2 in PD8 male rats is much higher than ... It is proved that Bcl-2 level in AVPV is higher whereas Bax level is lower in females than in males, just as being opposite of ... On the other hand, Bax, a proapoptotic protein, shows lower level in PD8 males than in PD8 females. Also, the number of active ... In MPNc, the levels of some proteins, which are related to apoptosis, were shown to be of significant difference between males ...
Its purified protein is composed of alpha and beta subunits in equal quantities. R-PC II has PCB at beta-84 and the ... When BCl-2 decreases, the expression of caspases increases. As a result, apoptosis occurs. C-PC alone is not enough to treat ... Stability of this protein invitro at these temperatures has been shown to be substantially lower. Photo-spectral analysis of ... These molecules decrease BCl-2 (regulator of apoptosis) production. Here, BCl-2 inhibits proteins called caspases. Caspases are ...
"Presenilin 1 protein directly interacts with Bcl-2". J. Biol. Chem. 274 (43): 30764-9. doi:10.1074/jbc.274.43.30764. PMID ... Levesque G (1999). "Presenilins interact with armadillo proteins including neural-specific plakophilin-related protein and beta ... They found that there is higher level expression of both proteins and a multidrug resistance-associated protein 1 (ABCC1) was ... "A new splice variant of glial fibrillary acidic protein, GFAP epsilon, interacts with the presenilin proteins". J. Biol. Chem. ...
14-3-3 proteins also contribute to the autoinhibition. As 14-3-3 proteins are all known to form constitutive dimers, their ... C-Raf has been shown to interact with: AKT1, ASK1, BAG1, BRAF, Bcl-2, CDC25A, CFLAR, FYN, GRB10, HRAS, HSP90AA1, KRAS, MAP2K1, ... Raf kinases A-Raf kinase B-Raf kinase KSR1 protein KSR2 protein GRCm38: Ensembl release 89: ENSMUSG00000000441 - Ensembl, May ... Yuryev A, Wennogle LP (February 2003). "Novel raf kinase protein-protein interactions found by an exhaustive yeast two-hybrid ...
... attaches to a protein called Bcl-2. This protein is present in high amounts in CLL cancer cells, where it helps the ... protein, leading to programmed cell death of CLL cells. Overexpression of Bcl-2 in some lymphoid malignancies has sometimes ... By attaching to Bcl-2 and blocking its actions, venetoclax causes the death of cancer cells and thereby slows down progression ... The apparent volume of distribution for venetoclax is approximately 256-321 L. It is highly bound to human plasma protein. ...
... resides on the outer mitochondrial membrane where it co-localizes with the apoptotic Bcl-2 family protein BID. MTCH2 ... February 2005). "Automated yeast two-hybrid screening for nuclear receptor-interacting proteins". Molecular & Cellular ... Gross A (August 2016). "BCL-2 family proteins as regulators of mitochondria metabolism". Biochimica et Biophysica Acta (BBA) - ... a clue to cracking the BCL-2 family riddle?". Journal of Bioenergetics and Biomembranes. 37 (3): 113-9. doi:10.1007/s10863-005- ...
... while studying the bcl-2 gene in follicular lymphoma, the most common human lymphoma. He studied for his B.Sc at Emory ... "The Bcl-2 protein family: arbiters of cell survival". Science. 281 (5381): 1322-6. doi:10.1126/science.281.5381.1322. PMID ... He is married to his fellow scientist and collaborator Suzanne Cory; they have 2 children. "ACRF Medical Research Advisory ...
5-MTHF: 5-methyltetrahydrofolate; 5,10-methyltetrahydrofolate; BAX: Bcl-2-associated X protein; BHMT: betaine-homocysteine S- ... It is substrate for the enzyme methylenetetrahydrofolate reductase (MTHFR)[1][2] It is mainly produced by the reaction of ... 5,10-Methylenetetrahydrofolate (N5,N10-Methylenetetrahydrofolate; 5,10-CH2-THF) is cofactor in several biochemical reactions. ... It is the one-carbon donor for thymidylate synthase, for methylation of 2-deoxy-uridine-5-monophosphate (dUMP) to 2-deoxy- ...
... is an inhibitor of the Bcl-2 family of proteins. This inhibition induces apoptosis in cancer cells, preventing tumor ... a Small-Molecule BCL-2 Family Antagonist, for Patients with Myelofibrosis". Clinical Lymphoma, Myeloma & Leukemia. 10 (4): 285- ... a small molecule pan-Bcl-2 family antagonist in patients with relapsed or refractory classical Hodgkin lymphoma". Blood. 119 (9 ... "Mechanisms of Antileukemic Activity of the Novel Bcl-2 Homology Domain-3 Mimetic GX15-070 (Obatoclax)". Cancer Research. 68 (9 ...
Many families of proteins act as negative regulators categorized into either antiapoptotic factors, such as IAPs and Bcl-2 ... The adenovirus E1B-55K protein and the hepatitis B virus HBx protein are examples of viral proteins that can perform such a ... these inhibitory proteins target retinoblastoma tumor-suppressing proteins. These tumor-suppressing proteins regulate the cell ... Finally, the Akt protein kinase promotes cell survival through two pathways. Akt phosphorylates and inhibits Bad (a Bcl-2 ...
BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 is a protein that in humans is encoded by the BNIP3 gene. BNIP3 is a ... Sequence similarity with Bcl-2 family members was not detected. Humans and other animals (Drosophila, Caenorhabditis), as well ... The dimeric mitochondrial protein encoded by this gene is known to induce apoptosis, even in the presence of BCL2. Change of ... BNIP3 interacts with the E1B 19 kDa protein which is responsible for the protection of virally induced cell death, as well as ...
WD-40 repeats are sequences around 40 amino acids long which end in Trp-Asp and are typically involved in protein-protein ... Members of the Bcl-2 family of pro-apoptotic proteins can induce the opening of the VDAC (12). This will cause the same release ... the inner membrane protein adenine nucleotide translocator (AdNT) and the matrix protein cyclophilin D (CyD) (12). This pore ... by acting on intracellular protein-protein interactions without altering the transcriptional levels of the apoptosome ...
Ras-related protein R-Ras is a protein that in humans is encoded by the RRAS gene. RRAS has been shown to interact with: ARAF, ... Fernandez-Sarabia MJ, Bischoff JR (November 1993). "Bcl-2 associates with the ras-related protein R-ras p23". Nature. 366 (6452 ... "Novel raf kinase protein-protein interactions found by an exhaustive yeast two-hybrid analysis". Genomics. 81 (2): 112-25. doi: ... Ohba Y, Mochizuki N, Yamashita S, Chan AM, Schrader JW, Hattori S, Nagashima K, Matsuda M (2000). "Regulatory proteins of R-Ras ...
... encodes a protein that activates apoptosis and interacts selectively with survival-promoting proteins Bcl-2 and Bcl-X(L)". EMBO ... Activator of apoptosis Hrk regulates apoptosis through interaction with death-repressor proteins Bcl-2 and Bcl-X(L). The HRK ... "Physical and functional interaction between BH3-only protein Hrk and mitochondrial pore-forming protein p32". Cell Death Differ ... HRK interacts with BCL2 and BCLXL via the BH3 domain, but not with the death-promoting BCL2-related proteins BAX, BAK, or BCLXS ...
Once triggered, it results in the diffusion of proteins from the space between the inner and outer mitochondrial membranes into ... Kalkavan, Halime; Green, Douglas R. (2018). "MOMP, cell suicide as a BCL-2 family business". Cell Death & Differentiation. 25 ( ... Initiation of MOMP involves Bcl-2 family proteins, including BAX and BAK. The outer mitochondrial membrane, typically permeable ... to molecules smaller than 5 kDa, forms pores during MOMP that allow it to accommodate proteins larger than 100 kDa. During MOMP ...
BCL2/adenovirus E1B 19 kDa protein-interacting protein 2 is a protein that in humans is encoded by the BNIP2 gene. This gene is ... Low BC, Lim YP, Lim J, Wong ES, Guy GR (November 1999). "Tyrosine phosphorylation of the Bcl-2-associated protein BNIP-2 by ... 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173-8. doi:10.1038 ... and GTPase-activating protein domains of a novel Rho GTPase-activating protein, BPGAP1". J. Biol. Chem. 278 (46): 45903-14. doi ...
... and there may be an increase in expression of the anti-apoptotic protein BCl-2. Many physicians over the centuries have tried ... 2001). "Mild hypothermia increases Bcl-2 protein expression following global cerebral ischemia". Brain Res. 95 (1-2): 75-85. ... "Induction of apoptosis in fibroblasts by c-myc protein". Cell. 69 (1): 119-28. doi:10.1016/0092-8674(92)90123-T. PMID 1555236. ... 50 (2): 244-57. doi:10.1016/j.brainresrev.2005.07.003. PMID 16216332. Stone BS, Zhang J, Mack DW, Mori S, Martin LJ, ...
The protein encoded by this gene belongs to the Bcl-2 family. Alternative splicing occurs at this locus and two transcript ... Induced myeloid leukemia cell differentiation protein Mcl-1 is a protein that in humans is encoded by the MCL1 gene. ... "Proapoptotic Bak is sequestered by Mcl-1 and Bcl-xL, but not Bcl-2, until displaced by BH3-only proteins". Genes Dev. 19 (11): ... The protein MCL1 has a very short biological half-life of only 20-30 minutes. The loss of MCL1 has a more dramatic impact than ...
... alpha interacting protein (synphilin), and SYPH1. This gene encodes a protein containing several protein-protein interaction ... "Lack of binding observed between human alpha-synuclein and Bcl-2 protein family". Neurosci. Lett. 316 (2): 103-7. doi:10.1016/ ... Synphilin-1 is a protein that in humans is encoded by the SNCAIP gene. SNCAIP stands for "synuclein, alpha interacting protein ... The SNCAIP gene provides instructions for making a protein called synphilin-1 and a slightly different version of this protein ...
Members of the Bcl-2 protein family regulate apoptosis by controlling the formation of MAC: the pro-apoptotic members Bax and/ ... by BCL-2 family proteins". Biochim Biophys Acta. 1762 (2): 191-201. doi:10.1016/j.bbadis.2005.07.002. PMID 16055309. Evgeny V. ... or Bak form MAC, whereas the anti-apoptotic members like Bcl-2 or Bcl-xL prevent MAC formation. Once formed, MAC mediates the ...
... endothelial cells have shown that both fisetin and quercetin induce apoptosis by inhibition of the anti-apoptotic protein Bcl- ... FOXO4 can bind with p53 protein to induce cellular senescence. A peptide competing with FOXO4 can act as a senolytic by ... Inhibitors of different members of the bcl-2 family of anti-apototic proteins. Studies of cell cultures of senescent human ... "Activity of the Bcl-2 Family Inhibitor ABT-263 in a Panel of Small Cell Lung Cancer Xenograft Models". Clinical Cancer Research ...
... it encodes both of the human proteins Bcl-xL and Bcl-xS. The protein encoded by this gene belongs to the BCL-2 protein family. ... Tagami S, Eguchi Y, Kinoshita M, Takeda M, Tsujimoto Y (Nov 2000). "A novel protein, RTN-XS, interacts with both Bcl-XL and Bcl ... Ayllón V, Cayla X, García A, Fleischer A, Rebollo A (Jul 2002). "The anti-apoptotic molecules Bcl-xL and Bcl-w target protein ... encodes a protein that activates apoptosis and interacts selectively with survival-promoting proteins Bcl-2 and Bcl-X(L)". The ...
The protein encoded by this gene belongs to the Bcl-2 protein family. Bcl-2 family members form hetero- or homodimers and act ... This protein contains a Bcl-2 homology domain 2 (BH2). The function of this gene has not yet been determined. Two alternatively ... 2001). "In vitro selection and characterization of Bcl-X(L)-binding proteins from a mix of tissue-specific mRNA display ... 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173-8. doi:10.1038 ...
The protein encoded by this gene belongs to the BCL-2 protein family. BCL-2 family members form hetero- or homodimers and act ... This protein can interact with other members of BCL-2 protein family including BCL2, BCL2L1/BCL-X(L), and BAX. Overexpression ... Ke N, Godzik A, Reed JC (2001). "Bcl-B, a novel Bcl-2 family member that differentially binds and regulates Bax and Bak". J. ... The mouse counterpart of this protein is found to interact with Apaf1 and forms a protein complex with Caspase 9, which ...
... is a protein that in humans is encoded by the BCL2L11 gene. The protein encoded by this gene belongs to the BCL-2 protein ... The protein encoded by this gene contains a Bcl-2 homology domain 3 (BH3). It has been shown to interact with other members of ... BCL-2 family members form hetero- or homodimers and act as anti- or pro-apoptotic regulators that are involved in a wide ... O'Connor L, Strasser A, O'Reilly LA, Hausmann G, Adams JM, Cory S, Huang DC (February 1998). "Bim: a novel member of the Bcl-2 ...
CNC patients have also been discovered with an unusually shortened PRKAR1α protein, detected in tumours and leukocytes, ... "Loss of Prkar1a leads to Bcl-2 family protein induction and cachexia in mice". Cell Death and Differentiation. 21 (11): 1815-24 ... "Mutations of the gene encoding the protein kinase a type I-alpha regulatory subunit in patients with the Carney complex". ... which is the gene encoding the regulatory R1α subunit of protein kinase A. Germline heterozygous PRKAR1α inactivation mutations ...
Hung WJ, Roberson RS, Taft J, Wu DY (May 2003). "Human BAG-1 proteins bind to the cellular stress response protein GADD34 and ... Wang HG, Takayama S, Rapp UR, Reed JC (July 1996). "Bcl-2 interacting protein, BAG-1, binds to and activates the kinase Raf-1 ... The protein encoded by this gene binds to BCL2 and is referred to as BCL2-associated athanogene. It enhances the anti-apoptotic ... At least three protein isoforms are encoded by this mRNA through the use of alternative translation initiation sites, including ...
"Amyotrophic lateral sclerosis-associated SOD1 mutant proteins bind and aggregate with Bcl-2 in spinal cord mitochondria". ... The mature protein is highly stable, but unstable when in its metal-free and disulfide-reduced forms. This manifests in vitro, ... The maturation process of this protein is complex and not fully understood, involving the selective binding of copper and zinc ... Two models suggest SOD1 inhibits apoptosis by interacting with BCL-2 proteins or the mitochondria itself. Most notably, SOD1 is ...
"Integrated strategy reveals the protein interface between cancer targets Bcl-2 and NAF-1". Proc. Natl. Acad. Sci. U.S.A. 111 ( ... The protein encoded by this gene is a zinc finger protein that localizes to the endoplasmic reticulum. The encoded protein ... Chang NC, Nguyen M, Germain M, Shore GC (February 2010). "Antagonism of Beclin 1-dependent autophagy by BCL-2 at the ... "A homozygous mutation in a novel zinc-finger protein, ERIS, is responsible for Wolfram syndrome 2". Am. J. Hum. Genet. 81 (4): ...
Homeobox protein Hox-D8 is a protein that in humans is encoded by the HOXD8 gene.[5][6][7] ... 1989). "Complementary homeo protein gradients in developing limb buds". Genes Dev. 3 (5): 641-50. doi:10.1101/gad.3.5.641. PMID ... HOXD8+protein,+human at the US National Library of Medicine Medical Subject Headings (MeSH) ... This article on a gene on human chromosome 2 is a stub. You can help Wikipedia by expanding it.. *v ...
ATBF1 · BCL(6、11A、11B) · CTCF · E4F1 · EGR(1、2、3、4) · ERV3 · GFI1 · GLI-Krüppel family(1、2、3、REST、S2、YY1) · HIC(1、2) · HIVEP(1、 ... Rb · RBL1(英语:Retinoblastoma-like protein 1) · RBL2(英语:Retinoblastoma-like protein 2) ... BBX(英语:BBX (gene)) · HMGB(1(英语:HMGB1)、2(英语:HMGB2)、3(英语:HMGB3)、4(英语:HMGB4)) · HMGN(英语:HMGN)、(1(英语:HMGN1)、2(英语:HMGN2)、3(英语:HMGN3) ... protein homodimerization activity. · sequence-specific DNA binding. · metal ion binding. · protein heterodimerization activity ...
Towards a proteome-scale map of the human protein-protein interaction network. „Nature". 437 (7062), s. 1173-8, 2005. DOI: ... Novel dipeptidyl proteasome inhibitors overcome Bcl-2 protective function and selectively accumulate the cyclin-dependent ... a b Ono T, Kitaura H, Ugai H, Murata T, Yokoyama KK, Iguchi-Ariga SM, Ariga H. TOK-1, a novel p21Cip1-binding protein that ... Regulation of cyclin A-Cdk2 by SCF component Skp1 and F-box protein Skp2. „Mol. Cell. Biol.". 19 (1), s. 635-45, 1999. PMID: ...
ATBF1 • BCL (6, 11A, 11B) • CTCF • E4F1 • EGR (2, 3) • ERV3 • GFI1 • GLI-Kruppel familija (1, 2, 3, REST, S2, YY1) • HIC (1, 2) ... Bernstein PL, Herrick DJ, Prokipcak RD, Ross J (1992). "Control of c-myc mRNA half-life in vitro by a protein capable of ... ARID (1A, 1B, 2, 3A, 3B, 4A) • CAP • IFI (16, 35) • MLL (2, 3, T1) • MNDA • NFY (A, B, C) • Ro/Sigma ... ARX • CDX (1, 2) • CRX • CUTL1 • DBX (1, 2) • DLX (3, 4, 5) • EMX2 • EN (1, 2) • FHL (1, 2, 3) • HESX1 • HHEX • HLX • Homeobox ...
Binding proteins: IGFBP (1, 2, 3, 4, 5, 6, 7). *Cleavage products/derivatives with unknown target: Glypromate (GPE, (1-3)IGF-1) ... a b Proto-Oncogene+Proteins+c-sis at the US National Library of Medicine Medical Subject Headings (MeSH) ... Hannink M, Donoghue DJ (1989). "Structure and function of platelet-derived growth factor (PDGF) and related proteins". Biochim ... 28A (2): 102-8. doi:10.1007/BF02631013. PMID 1537750.. *^ "Researchers make older beta cells act young again". Eurekalert.org. ...
protein binding. • protease binding. • tumor necrosis factor receptor binding. • cytokine activity. • identical protein binding ... For instance, NF-κB enhances the transcription of C-FLIP, Bcl-2, and cIAP1 / cIAP2, inhibitory proteins that interfere with ... positive regulation of protein complex assembly. • protein kinase B signaling. • positive regulation of cytokine production. • ... protein localization to plasma membrane. • positive regulation of protein catabolic process. • regulation of receptor activity ...
Uses: M-protein level in the blood is standard of care and is used for almost all patients with multiple myeloma. Patient- ... Jun 2006). "The bcl-2/IgH rearrangement in a population of 204 healthy individuals: occurrence, age and gender distribution, ... Targets: M-protein levels in blood, patient-specific assays for immunoglobulin and T cell receptor genes (high levels of ... These proteins can be stained with fluorescent dye labeled antibodies and detected using flow cytometry. The limit of detection ...
Wiskott-Aldrich syndrome protein verprolin homologous-1 (WAVE-1) dan Bcl-xL akan membentuk kompleks protein mitokondrial untuk ... Myelin basic protein (MBP)[sunting , sunting sumber]. Bagian ini tidak memiliki referensi atau sumber tepercaya sehingga isinya ... Protein tau (TP)[sunting , sunting sumber]. Bagian ini tidak memiliki referensi atau sumber tepercaya sehingga isinya tidak ... Fatty acid-binding proteins (FABPs)[sunting , sunting sumber]. Bagian ini tidak memiliki referensi atau sumber tepercaya ...
The protein ZIP1 is responsible for the active transport of zinc into prostate cells. One of the zinc's important roles is to ... The upregulation of BCL-2 after androgen ablation in prostate carcinoma cell lines and in a castrated-male rat model further ... Prostate specific membrane antigen is a transmembrane carboxypeptidase and exhibits folate hydrolase activity.[75] This protein ... The absence of zinc is thought to occur via a silencing of the gene that produces the transporter protein ZIP1. ZIP1 is now ...
tyrosine phosphorylation of STAT protein. • positive regulation of tyrosine phosphorylation of STAT protein. • regulation of ... In rodent lymphocytes, IL-15 prevents apoptosis by inducing BCL2L1/BCL-x(L), an inhibitor of the apoptosis pathway.[10] In ... protein binding. • cytokine receptor binding. • cytokine activity. Cellular component. • cell nucleus. • integral component of ... mitogen-activated protein kinase) kinase pathway and the phosphorylation of Lck (lymphocyte-activated protein tyrosine kinase) ...
protein binding. • heme binding. • electron carrier activity. Cellular component. • cytosol. • protein phosphatase type 2A ... BAK1/Bcl-2 homologous antagonist killer. Bcl-2-associated death promoter. Anti-apoptotic:. Bcl-2. Bcl-xL. ... Soltys BJ, Gupta RS (2000). "Mitochondrial proteins at unexpected cellular locations: export of proteins from mitochondria from ... "Effect of constitutive 70-kDa heat shock protein polymerization on its interaction with protein substrate". The Journal of ...
protein binding. • cyclin-dependent protein serine/threonine kinase inhibitor activity. • ubiquitin protein ligase binding. • ... role of bcl-2, and the cyclin dependent kinase inhibitors P27 and P21". Leuk. Lymphoma. 43 (1): 51-7. doi:10.1080/ ... cyclin-dependent protein serine/threonine kinase activity. • protein kinase inhibitor activity. • protein kinase binding. • ... This article is about the p21Cip1 protein. For the p21/ras protein, see Ras (protein). For other uses, see P21 (disambiguation) ...
Hepatocyte nuclear factor 3-gamma (HNF-3G), also known as forkhead box protein A3 (FOXA3) or transcription factor 3G (TCF-3G) ... protein domain specific binding. • RNA polymerase II transcription factor activity, sequence-specific DNA binding. ... HNF-3G is a member of the forkheadclass of DNA-binding proteins. These hepatocyte nuclear factors are transcriptional ... Dintilhac A, Bernués J (2002). "HMGB1 interacts with many apparently unrelated proteins by recognizing short amino acid ...
Por exemplo, o NF-κB potencia a transcrición de C-FLIP, Bcl-2, e cIAP1 / cIAP2, proteínas inhibidoras que interfiren coa ... "A novel form of TNF/cachectin is a cell surface cytotoxic transmembrane protein: ramifications for the complex physiology of ... que induce a expresión de Mn-SOD e Bcl-2. Véxase tamén a sección nomenclatura para a proposta moderna de denominar ao TNFα ... Cell Biol. 6 (2): 97-105. PMID 14743216. doi:10.1038/ncb1086.. *↑ Micheau O, Tschopp J (July 2003). "Induction of TNF receptor ...
Manipulation of apoptosis regulator proteins Bcl-2 and Bax (overexpression of Bcl-2 or deletion of Bax) produces an increase in ... and the scaffold protein FIP200. Class III PI3K complex, containing hVps34, Beclin-1, p150 and Atg14-like protein or ... Additionally, Bcl-2 inhibits Beclin-1-dependent autophagy, thereby functioning both as a pro-survival and as an anti-autophagic ... It has also been shown that in mice null for the proapoptotic factor Bax (Bcl-2-associated X protein) a larger percentage of ...
... protein that promote osteoclast formation. Oxidative stress results when ethanol induces NOX expression, resulting in ROS ... "Spatial distribution of Bax and Bcl-2 in osteocytes after bone fatigue: complementary roles in bone remodeling regulation?". ... 54 (2): 55-9. doi:10.2302/kjm.54.55. PMID 16077253. Maddalozzo, G. F.; Turner, R. T.; Edwards, C. H. T.; Howe, K. S.; Widrick, ... 26 (2): 229-238. doi:10.1002/jbmr.320. ISSN 1523-4681. PMC 3179345 . PMID 21254230. Verborgt, Olivier; Tatton, Nadine A.; ...
Rob M Ewing, Chu Peter, Elisma Fred, Li Hongyan, Taylor Paul, et al., Large-scale mapping of human protein-protein interactions ... Bcl-2,[17] SUPT3H,[14] SAP130,[14] DNMT3A,[18] SMAD3,[19] MAX,[20][21][22][23][24][25][26][27][28][29][30][31][32] SMAD2,[19] ... Gazin C, Rigolet M, Briand JP, et al., Immunochemical detection of proteins related to the human c-myc exon 1, in EMBO J., vol ... Q Guo, Xie J, Dang C V, Liu E T, Bishop J M, Identification of a large Myc-binding protein that contains RCC1-like repeats (PDF ...
... is caused by a reaction to gliadins and glutenins (gluten proteins)[49] found in wheat, and similar proteins ... "BCL Newsletter. United States Conference of Catholic Bishops. November 2003. Archived from the original on 2 January 2007. ... These are storage proteins rich in proline (prol-) and glutamine (-amin) that dissolve in alcohols and are resistant to ... The vast majority of people with coeliac have one of two types of the HLA-DQ protein.[62] HLA-DQ is part of the MHC class II ...
"Chapter 1: Proteins are the Body's Worker Molecules". The Structures of Life. National Institute of General Medical Sciences. ... Pinaghugot gikan sa "https://bcl.wikipedia.org/w/index.php?title=Asidong_amino&oldid=205142" ... Bistado sinda bilang 2-, alpha-, o α-asidong amino (harus henerikong pormula na H2NCHRCOOH, kun sain an R iyo sarong organikong ... An mga asidong amino (Ingles: amino acid) iyo mga organikong kompuwesto na igwang amino (-NH2) asin carboxyl (-COOH) na ...
... which is facilitated by binding to adaptor proteins via protein-protein interaction motifs that are collectively referred to as ... Simple explanation of the mechanisms of apoptosis triggered by internal signals (bcl-2), along the caspase-9, caspase-3 and ... 7 (2): 99-109. doi:10.1038/nrmicro2070. PMC 2910423. PMID 19148178.. *^ a b c d e f Eldridge, Matthew JG; Shenoy, Avinash R ( ... The adaptor protein FADD will recruit (by a Death domain-Death domain interaction) pro-Caspase 8 via the DED domain. This FasR ...
ATBF1 • BCL (6, 11A, 11B) • CTCF • E4F1 • EGR (2, 3) • ERV3 • GFI1 • GLI-Kruppel familija (1, 2, 3, REST, S2, YY1) • HIC (1, 2) ... Protein kodiran ovim genom je član NR1 potfamilije nuklearnih hormonskih receptora. To je DNA-vezujući protein koji se može ... ARID (1A, 1B, 2, 3A, 3B, 4A) • CAP • IFI (16, 35) • MLL (2, 3, T1) • MNDA • NFY (A, B, C) • Ro/Sigma ... 2000). "Differential ligand-dependent protein-protein interactions between nuclear receptors and a neuronal-specific cofactor ...
ATBF1 • BCL (6, 11A, 11B) • CTCF • E4F1 • EGR (2, 3) • ERV3 • GFI1 • GLI-Kruppel familija (1, 2, 3, REST, S2, YY1) • HIC (1, 2) ... Signal provodeći adapterski protein: Gradivni protein. Drugi glasnik: cAMP-zavisni put • Ca2+ signalizacija • Lipidna ... B enzm: 1.1/2/3/4/5/6/7/8/10/11/13/14/15-18, 2.1/2/3/4/5/6/7/8, 2.7.10, 2.7.11-12, 3.1/2/3/4/5/6/7, 3.1.3.48, 3.4.21/22/23/24, ... ARID (1A, 1B, 2, 3A, 3B, 4A) • CAP • IFI (16, 35) • MLL (2, 3, T1) • MNDA • NFY (A, B, C) • Ro/Sigma ...
SREB proteins are indirectly required for cholesterol biosynthesis and for uptake and fatty acid biosynthesis. These proteins ... proteins. However, in contrast to E-box-binding HLH proteins, an arginine residue is replaced with tyrosine making them capable ... SREBP precursors are retained in the ER membranes through a tight association with SCAP and a protein of the INSIG family. ... Sterol regulatory element-binding proteins (SREBPs) are transcription factors that bind to the sterol regulatory element DNA ...
protein binding. • ankyrin binding. • gamma-catenin binding. • beta-catenin binding. • GTPase activating protein binding. • ... Oneyama C, Nakano H, Sharma SV (March 2002). "UCS15A, a novel small molecule, SH3 domain-mediated protein-protein interaction ... Several proteins such as SNAI1/SNAIL,[58][59] ZFHX1B/SIP1,[60] SNAI2/SLUG,[61][62] TWIST1[63] and DeltaEF1[64] have been found ... identical protein binding. Cellular component. • cell-cell adherens junction. • apical junction complex. • trans-Golgi network ...
13(S)-HpODE, and 13(S)-HODE directly activate human (but not mouse) GPR132 (G protein coupled receptor 132, also termed G2A) in ... but also promotes its cell survival by stimulating production and of insulin-like growth factor 1 and possibly altering the Bcl ... Blackburn, Mary L; Podgorski, Izabela; Bull, Arthur W (1999). "Specific protein targets of 13-oxooctadecadienoic acid (13-OXO) ... 18 (2): 349-56. doi:10.1021/tx049685x. PMID 15720142.. *^ a b c d Yoshida, Yasukazu; Umeno, Aya; Akazawa, Yoko; Shichiri, ...
... arrest and cellular apoptosis via the accumulation of cytosolic p53 and subsequent activation of Bcl-2-associated X protein, an ... Chlorambucil was approved for medical use in the United States in 1957.[2] It is on the World Health Organization's List of ... InChI=1S/C14H19Cl2NO2/c15-8-10-17(11-9-16)13-6-4-12(5-7-13)2-1-3-14(18)19/h4-7H,1-3,8-11H2,(H,18,19) Y ... Common side effects include bone marrow suppression.[2] Other serious side effects include an increased long term risk of ...
protein binding. • ligand-dependent nuclear receptor binding. • transcription factor activity, RNA polymerase II distal ... "Inactivation of caspase-8 on mitochondria of Bcl-xL-expressing MCF7-Fas cells: role for the bifunctional apoptosis regulator ... Seol W, Choi HS, Moore DD (Jan 1995). "Isolation of proteins that interact specifically with the retinoid X receptor: two novel ... Seol W, Choi HS, Moore DD (Jan 1995). "Isolation of proteins that interact specifically with the retinoid X receptor: two novel ...
This protein family, which provides the framework for controlling apoptosis, takes its name from a type of cancer called B-cell ... BCL-2, the first family member, forms the molecular basis for sustaining the lymphoma cancer cells. The BCL-2 family of ... in mammals known as the BCL-2 protein family. ... BCL-2. protein. THIS IS A DIRECTORY PAGE. Britannica does not ... BCL-2, the first family member, forms the molecular basis for sustaining the lymphoma cancer cells. The BCL-2 family of ...
LSBio BCL2L14 / BCL-G Proteins [LifeSpan BioSciences, Inc.] LSBio BCL2L14 / BCL-G Proteins. LifeSpan BioSciences, Inc. ... Ubiquitin-like protein MNSFβ covalently binds to Bcl-G and enhances lipopolysaccharide/interferon γ-induced apoptosis in ... Ubiquitin-like protein MNSFβ covalently binds to Bcl-G and enhances lipopolysaccharide/interferon γ-induced apoptosis in ... LSBio BCL2L14 / BCL-G Antibodies [LifeSpan BioSciences, Inc.] LSBio BCL2L14 / BCL-G Antibodies. LifeSpan BioSciences, Inc. ...
The anti-apoptotic protein, Bcl-2, interacts with the evolutionarily conserved autophagy protein, Beclin 1. However, little is ... but also as an antiautophagy protein via its inhibitory interaction with Beclin 1. This antiautophagy function of Bcl-2 may ... Bcl-2 antiapoptotic proteins inhibit Beclin 1-dependent autophagy.. Pattingre S1, Tassa A, Qu X, Garuti R, Liang XH, Mizushima ... Here, we show that wild-type Bcl-2 antiapoptotic proteins, but not Beclin 1 binding defective mutants of Bcl-2, inhibit Beclin ...
"Identification of the protein-protein contact site and interaction mode of human VDAC1 with Bcl-2 family proteins". Biochem. ... "Entrez Gene: BCL2-associated X protein". Oltvai ZN, Milliman CL, Korsmeyer SJ (August 1993). "Bcl-2 heterodimerizes in vivo ... This protein forms a heterodimer with BCL2, and functions as an apoptotic activator. This protein is reported to interact with ... For instance, binding of HA-BAD to BCL-xL and concomitant disruption of BAX:BCL-xL interaction was found to partly reverse ...
This cell death was inhibited by knockdown of the autophagy protein ATG5 by RNAi. Thus, Bcl-2 appears to be a more general ... Bcl-2 is well known for its role as an antiapoptotic protein, and Pattingre et al. now show that Bcl-2 also inhibits autophagy ... Knockdown of Bcl-2 in HeLa cells with siRNA resulted in an increase in the number of autophagic structures under starvation ... In MCF7 cells (which do not have wild-type beclin 1), expression of mutant forms of beclin 1 that could not bind Bcl-2 caused ...
In addition to the regulation of apoptosis, BCL-2 proteins at the ER also regulate autophagy, a survival pathway that limits ... Although initially identified as central regulators of apoptosis at the level of mitochondria, an important role for BCL-2 ... and the BCL-2 family is almost invariably implicated in the regulation of these pathways. This also includes Ca2+-mediated ... with particular emphasis on the BCL-2 family proteins. ... proteins at the endoplasmic reticulum is now well established. ...
In nonapoptotic cells the proapoptotic BCL-2 proteins BAX and BAK but also prosurvival family members, like... ... BCL-2 proteins control stress-dependent commitment to the programmed cell death apoptosis. ... BCL-2 proteins Mitochondria Apoptosis Retrotranslocation BH3-only proteins This is a preview of subscription content, log in to ... The retrotranslocation of BCL-2 proteins from the OMM can be measured using fluorescence-labeled protein in intact cells or ...
The PDB archive contains information about experimentally-determined structures of proteins, nucleic acids, and complex ... Association to the apoptosis repressors Bcl-X(L), BHRF1, Bcl-2 or its adenovirus homolog E1B 19k protein suppresses this death- ... Protein Feature View of PDB entries mapped to a UniProtKB sequence * Number of PDB entries for Q13323: no matching PDB entries ... This protein in other organisms (by gene name): Q13323 - Homo sapiens 0 * O70337 - Mus musculus no matching PDB entries ...
Bcl-2 family members are essential for maintenance of major organ systems, and mutations affecting them are implicated in ... Bcl-2 and related cytoplasmic proteins are key regulators of apoptosis, the cell suicide program critical for development, ... Those most similar to Bcl-2 promote cell survival by inhibiting adapters needed for activation of the proteases (caspases) that ... apparently through mechanisms that include displacing the adapters from the pro-survival proteins. Thus, for many but not all ...
Mouse models to study the Bcl-2 family of proteins Lead researcher. Dr Philippe Bouillet, Dr Gabrielle Belz ...
BHRF1 or Bcl-2 suppresses this death-promoting activity. ... Binding to the apoptosis repressors Bcl-X(L), ... View protein in Pfam. PF12201 bcl-2I13, 1 hit. ProDomi. View protein in ProDom or Entries sharing at least one domain. ... Protein-protein interaction databases. ComplexPortali. CPX-310 BIK:BCL-w complex. ... to allow unambiguous identification of a protein.,p>,a href=/help/protein_names target=_top>More...,/a>,/p>Protein namesi. ...
Bcl-2 or its adenovirus homolog E1B 19k protein suppresses this death-promoting activity. Does not interact with BAX. ... Association to the apoptosis repressors Bcl-X(L), BHRF1, ... View protein in Pfam. PF12201. bcl-2I13. 1 hit. ProDom; a ... Protein. Similar proteins. Organisms. Length. Cluster ID. Cluster name. Size. Q13323. A0A024R4X6. Homo sapiens (Human). 160. ... to allow unambiguous identification of a protein.,p>,a href=/help/protein_names target=_top>More...,/a>,/p>Protein namesi. ...
Bcl-xL) or promote (e.g. Bax, Bcl-xS, Bak) apoptosis. Bcl-2 inhibits apoptosis by preventing the release ... If the Bcl-2 level is higher than the Bax level, apoptosis will be prohibited. The ratio of Bcl-2 to Bax in the cell can ... Some cancer cells, such as melanoma, overexpress Bcl-2 preventing apoptosis and allowing malignant growth to continue.
... Bcl-2 is a member of a large gene family encoding proteins that can either inhibit (e.g. Bcl-2, ...
Bcl-2 Protein Targeting by the p53/p21 Complex-Response. Eun Mi Kim, Jongdoo Kim and Hong-Duck Um ... Bcl-2 Protein Targeting by the p53/p21 Complex-Response Message Subject (Your Name) has forwarded a page to you from Cancer ... Bcl-w promotes cell invasion by blocking the invasion-suppressing action of Bax. Cell Signal 2012;24:1163-72. ... Interactions of endogenous proteins p53 and p21 in IMR-32 neuroblastoma and H460 lung cancer cells. A, IMR-32 cell lysates were ...
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The expression profile of 93 genes involved in apoptosis as well as the protein level of BCL-2 family proteins were then ... Finally, the modulation of the abundance and/or of the post-translational modifications of most proteins of the BCL-2 family by ... hypoxia decreased the abundance of nearly all the pro-apoptotic BCL-2 family proteins while none of them are decreased in A549 ... are important mediators of etoposide-induced cell death in HepG2 cells and the hypoxia-induced modification of these proteins ...
BCL2 was the first cloned component of the mechanism for apoptosis - the process by which metazoan cells commit suicide - to ... BH3 peptide fits into a hydrophobic groove on the surface of Bcl‐x. The BH3 of Bcl‐x itself is coloured green. Note that Bcl‐x ... and Bok (middle, purple symbol) and BH3‐only proteins (top, green symbol). All BCL2 family members bear a number of BCL2 ... only proteins on the mitochondrial outer membrane. In healthy (non‐apoptotic) cells, only small amounts of antiapoptotic BCL. ‐ ...
Its three sub-families have distinct roles: the BH3-only proteins trigger apoptosis by binding via their BH3 domain to pro- ... Commitment of cells to apoptosis is governed largely by protein-protein interactions between members of the Bcl-2 protein ... Commitment of cells to apoptosis is governed largely by protein-protein interactions between members of the Bcl-2 protein ... Some BH3-only proteins also bind to Bax and Bak. Whether Bax and Bak are activated directly by these BH3-only proteins, or ...
Vesicular Stomatitis Virus Induces Apoptosis Primarily through Bak Rather than Bax by Inactivating Mcl-1 and Bcl-XL Alicia F. ... Bcl-2 Blocks Accretion or Depletion of Stored Calcium but Has No Effect on the Redistribution of IP3 Receptor I Mediated by ... Epstein-Barr Virus-Encoded Bcl-2 Homologue Functions as a Survival Factor in Wp-Restricted Burkitt Lymphoma Cell Line P3HR-1 ... The Hepatitis C Virus Core Protein Contains a BH3 Domain That Regulates Apoptosis through Specific Interaction with Human Mcl-1 ...
Bcl-2 Protein Targeting by the p53/p21 Complex-Letter. Liz J. Hernandez Borrero, Rahmat Sikder, Amriti Lulla, Prashanth Gokare ... Bcl-2 Protein Targeting by the p53/p21 Complex-Letter. Liz J. Hernandez Borrero, Rahmat Sikder, Amriti Lulla, Prashanth Gokare ... Bcl-2 Protein Targeting by the p53/p21 Complex-Letter. Liz J. Hernandez Borrero, Rahmat Sikder, Amriti Lulla, Prashanth Gokare ... It is important to document endogenous protein:protein interactions and to include critical controls to support novel paradigm- ...
Silent mating-type information regulation 2 homologue 1 (SIRT1), a member of the class III histone deacetylase (HDAC) family, ... Following treatment with sirtinol (inhibitor of SIRT1), the expression of the pro-survival protein Bcl-2 was markedly decreased ... SIRT1 Suppresses Breast Cancer Growth Through Downregulation of the Bcl-2 Protein Oncol Rep. 2013 Jul;30(1):125-30. doi: ... Silent mating-type information regulation 2 homologue 1 (SIRT1), a member of the class III histone deacetylase (HDAC) family, ...
... was analyzed and Bcl-2/Bad ratio in the follicular apparatus of the rat ovary was determined on day... ... proapoptotic protein Bad and anti-apoptotic protein Bcl-2) ... proapoptotic protein Bad and anti-apoptotic protein Bcl-2) was ... Expression of Bcl-2 Family Proteins in the Ovarian Follicular Apparatus in the Acute Period after Experimental Hyperthermia. ... apoptosis hyperthermia ovarian follicular apparatus Bcl-2/Bad Translated from Byulleten Eksperimentalnoi Biologii i Meditsiny ...
... Metastatic melanoma is one of the most difficult cancers to cure and recent ... There is some evidence that Bcl-2 pro-survival proteins (which normally keep cells alive by inhibiting the cell death program ... Our research aims to identify the key Bcl-2 pro-survival proteins that are responsible for melanoma survival. This will be ... The second aim is to determine whether resistance to current melanoma treatment arises due to elevated levels of Bcl-2 pro- ...
bcl2-Associated X Protein Isoform beta*bcl2-Associated X Protein Isoform beta ... bcl2-Associated X Protein Isoform sigma*bcl2-Associated X Protein Isoform sigma ... bcl2-Associated X Protein Isoform omega*bcl2-Associated X Protein Isoform omega ... bcl2-Associated X Protein Isoform alpha*bcl2-Associated X Protein Isoform alpha ...
Investigating the requirement of pro-survival Bcl-2 family proteins in leukaemia Lead researcher. Dr Stephan Glaser ...
B) Summary of protein-protein interactions between pairs of pro-apoptotic proteins (Bok, Bak, Bik, and Bax) and different anti- ... Bcl-xL, and Bcl-w) anti-apoptotic proteins. Coupled with findings showing that Bok-induced apoptosis could only be antagonized ... Bcl-xL, and Bcl-w. We further tested interactions between Bok and several pro-apoptotic Bcl-2 proteins (Fig. 2A). Of interest, ... Bcl-xL, Bcl-w, BAD, Bax, Bak, or Bik fused to the GAL4 binding domain. In addition, prominent growth of colonies expressing Bcl ...
Increase in Bcl-2 phosphorylation and reduced levels of BH3-only Bcl-2 family proteins in kainic acid-mediated neuronal death ... Korhonen, L., Belluardo, N., Mudo, G. and Lindholm, D. (2003), Increase in Bcl-2 phosphorylation and reduced levels of BH3-only ... Bcl-2 family proteins in kainic acid-mediated neuronal death in the rat brain. European Journal of Neuroscience, 18: 1121-1134 ... 2. Department of Experimental Medicine, Section of Human Physiology, Faculty of Medicine, University of Palermo, Palermo, Italy ...
Among the proteins involved in this response are nutrient-deprivation autophagy factor-1 (NAF-1)- and Bcl-2. NAF-1 is a ... A combination of the solution studies together with a new application of DCA to the eukaryotic proteins NAF-1 and Bcl-2 ... Integrated strategy reveals the protein interface between cancer targets Bcl-2 and NAF-1.. [Sagi Tamir, Shahar Rotem-Bamberger ... NAF-1 binds to both the pro- and antiapoptotic regions (BH3 and BH4) of Bcl-2, as demonstrated by a nested protein fragment ...
To gain better understanding of how this protein functions, we have undertaken a... ... The Bcl-2 protein blocks a distal step in an evolutionarily conserved pathway for programmed cell death and apoptosis. ... two proteins that we have shown can associate with protein complexes containing Bcl-2 and which cooperate with Bcl-2 to ... H. Zha, C. Aime-Sempe, T. Sato and J.C. Reed, Pro-apoptotic protein Bax heterodimerizes with Bcl-2 and homodimerizes with Bax ...
HIF-1α and HSP90 proteins form a tri-complex that may contribute to enhancing the stability of the HIF-1α protein in bcl-2 ... Conclusions/Significance We identified the stabilization of HIF-1α protein as a mechanism through which bcl-2 induces the ... the current study identified HIF-1α protein stabilization as a key regulator for the induction of HIF-1 by bcl-2 under hypoxia ... but it was not dependent on the prolyl hydroxylation of HIF-1α protein. We also showed that bcl-2, ...
  • Immunoprecipitated BCL-2 from Jurkat-BCL-2 cells treated with paclitaxel was incubated with λPPase at 30°C for 30 min with or without phosphatase inhibitors (50 mM NaF, 2 mM sodium orthovanadate, 5 mM EDTA, and 5 mM EGTA). (asm.org)
  • The antiapoptotic members of the Bcl-2 protein family (Bcl-2, Bcl-X L , and Mcl-1) are important inhibitors of apoptosis, but have not been investigated extensively in cholangiocarcinoma. (bmj.com)
  • This report reviews the recent progress of structures, functions and inhibition of Bcl-2 family proteins, especially the development of Bcl-2 inhibitors in past decades as anticancer agents. (eurekaselect.com)
  • INHIBITORS OF PROSURVIVAL BCL-2 PROTEINS Small organic molecules Obatoclax This synthetic indol bipyrrole molecule derived from the natural product prodigiosin is capable of binding to all prosurvival BCL-2 family proteins with low affinity (in the M range) and inducing apoptosis in tumor cells [17]. (immune-source.com)
  • Membrane proteins encoded by the BCL-2 GENES and serving as potent inhibitors of cell death by APOPTOSIS. (rush.edu)
  • Vaccinia virus (VACV) encodes many immunomodulatory proteins, including inhibitors of apoptosis and modulators of innate immune signalling. (ox.ac.uk)
  • The most prominent effect elicited by microtubule inhibitors is the phosphorylation of the antiapoptotic proteins, Bcl-2 and Bcl-xL. (grantome.com)
  • Small molecule inhibitors of Bcl-2 proteins were investigated for their ability to sensitize a range of leukemia cell lines to vinblastine . (dartmouth.edu)
  • Although initially identified as central regulators of apoptosis at the level of mitochondria, an important role for BCL-2 proteins at the endoplasmic reticulum is now well established. (nature.com)
  • In nonapoptotic cells the proapoptotic BCL-2 proteins BAX and BAK but also prosurvival family members, like BCL-x L or MCL-1, translocate to the outer mitochondrial membrane (OMM) and retrotranslocate from the mitochondria back into the cytosol. (springer.com)
  • Martinou J-C, Youle RJ (2011) Mitochondria in apoptosis: Bcl-2 family members and mitochondrial dynamics. (springer.com)
  • Todt F, Cakir Z, Reichenbach F, Youle RJ, Edlich F (2013) The C-terminal helix of Bcl-x(L) mediates Bax retrotranslocation from the mitochondria. (springer.com)
  • Bcl-2 inhibits apoptosis by preventing the release of Apoptosis Inducing factor (AIF) and cytochrome c from mitochondria. (sigmaaldrich.com)
  • The BCL-2 family of proteins constitutes a critical control point in apoptosis residing immediately upstream of irreversible cellular damage, where family members control the release of apoptogenic factors from mitochondria. (aacrjournals.org)
  • Tsujimoto, Y. Role of Bcl-2 family proteins in apoptosis: apoptosomes or mitochondria. (springer.com)
  • Shimizu, S., Shinohara, Y. and Tsujimoto, Y. Bax and Bcl-xL independently regulate apoptotic changes of yeast mitochondria that require VDAC but not adenine nucleotide translocator. (springer.com)
  • 17 Some members of the Bcl-2 protein family when bound to the mitochondria regulate the function of the large polymeric channel, permeability transition pore complex, 18 located at the point of contact between the inner and the outer mitochondrial membranes. (bmj.com)
  • Mor … More eover, intracellular acidification, translocation of Bax, a pro-apoptotic protein, from cytosol to mitochondria, opening of mitochondrial permeability transition pore, loss of mitochondrial membrane potential, cytochrome c release from mitochondria into cytosol, and activation of caspase-9 and 3 were observed in a pH-dependent fashion. (nii.ac.jp)
  • In many types of normal cells, BAD immunoreactivity was associated with cytosolic organelles resembling mitochondria, suggesting that BAD is often heterodimerized with other Bcl-2 family proteins in vivo. (elsevier.com)
  • He then looks at the molecular machinery that links signals that cause cell death to caspases, emphasizing the importance of the BCL-2 family of proteins and the role of cytochrome c released from mitochondria. (cshlpress.org)
  • Caspase-2 failed to induce cytochrome c release from mitochondria with Bid -/- background, and the release could be restored by addition of the wild-type Bid protein, but not by Bid with the caspase-2 cleavage site mutated. (elsevier.com)
  • Caspase-2 was not able to induce cytochrome c release from Bax -/- Bak -/- mitochondria either. (elsevier.com)
  • Furthermore, this work has also shown the potential of scanning Fluorescence Correlation Spectroscopy (FCS) as a tool to measure interactions of Bcl-2 proteins in the mitochondria of living cells. (uni-tuebingen.de)
  • I first validated scanning FCS' applicability using green fluorescent protein (GFP) targeted to mitochondria. (uni-tuebingen.de)
  • Using two color FCS, I report for the first time, to the best of my knowledge, a calculated dissociation constant between truncated Bid and anti-apoptotic member, Bcl-xL, in the mitochondria. (uni-tuebingen.de)
  • Intact BH3 motif is required by BIK, BID, BAK, BAD and BAX for their pro-apoptotic activity and for their interaction with anti-apoptotic members of the Bcl-2 family. (rcsb.org)
  • A major mechanism by which mammalian cells kill themselves involves members of the BCL‐2 family of proteins, some of which promote cell death, and others which inhibit cell death. (els.net)
  • In particular, recent advances in understanding the interplay between distinct members of the BCL-2 family and the molecular mechanisms underlying their regulation of MOMP are described. (aacrjournals.org)
  • Bcl-2 homology-3 domain (BH3)-only proteins are pro-apoptotic members of the Bcl-2 family whose enhanced expression acts as a trigger for the intrinsic apoptotic cascade. (frontiersin.org)
  • Prosurvival members of the Bcl-2 family (Bcl-2, Bcl-x L , Bcl-w, Mcl-1, and A1) prevent Bax/Bak activation and thereby preclude MOMP and apoptosis. (rupress.org)
  • In response, they unleash the apoptotic cascade by inactivating the protective function of the pro-survival members of the Bcl-2 family and by activating the Bax/Bax-like pro-apoptotic family members. (biologists.org)
  • Amongst the members of the Bcl-2 family, the BH3-only proteins have now been recognised as essential initiators of programmed cell death and stress-induced apoptosis ( Huang and Strasser, 2000 ). (biologists.org)
  • The expression of caspases and members of the Bcl-2 family was examined through immunoblot analysis. (springermedizin.de)
  • Targeting the anti-apoptotic members of the Bcl-2 family of proteins is proving to be a successful way to selectively target cancer cells and induce apoptosis. (biomedcentral.com)
  • Due to the myriad interactions between prosurvival and proapoptotic members of the Bcl-2 family of proteins, establishing the mechanisms that regulate the intrinsic apoptotic pathway has proven challenging. (rcsb.org)
  • Overexpression of Bcl-2 suppresses apoptosis induced by a variety of agents both in vitro and in vivo ( 10 ). (pnas.org)
  • It has also been found that the anti-apoptotic effect of Bcl-2 is not universal because Bcl-2 overexpression is not effective in blocking Fas-mediated apoptosis and the apoptosis of autoreactive thymocytes during negative selection ( 13 , 14 ). (pnas.org)
  • In recent years, a rising number of biological dysfunctions involved in SCLC pathogenesis were reported, including ectopic expression of neuroendocrine regulatory peptides, overexpression of Myc family oncogenes and extracellular matrix proteins, as well genetic abnormalities in the tumor suppressor genes p53 and pRB ( 1 , 2 ). (aacrjournals.org)
  • A recent study demonstrated the lack of beta-amyloid (Aβ) plaque formation and accumulation of the amyloid precursor protein (APP) in a triple transgenic mouse model of Alzheimer's disease (3xTg-AD) following overexpression of the anti-apoptotic protein, Bcl-2 (Rohn et al. (pubmedcentralcanada.ca)
  • Overexpression of Bcl-2 prevented caspase activation, the caspase cleavage of tau and improved place recognition memory in 3xTg-AD mice [ 8 ]. (pubmedcentralcanada.ca)
  • An additional finding of that study was the accumulation of full-length APP and tau following overexpression of Bcl-2 in 3xTg-AD mice [ 8 ]. (pubmedcentralcanada.ca)
  • The interpretation of this finding was the observed accumulation of APP and tau resulted from an inhibition in caspasemediated proteolysis following overexpression of Bcl-2. (pubmedcentralcanada.ca)
  • However, direct demonstration that APP is cleaved by caspases and is prevented following overexpression of Bcl-2 was not investigated. (pubmedcentralcanada.ca)
  • 6 ], we now demonstrate caspase-cleavage of APP does occur in 3xTgAD mice and is prevented along with the formation of extracellular deposits of Aβ following overexpression of Bcl-2. (pubmedcentralcanada.ca)
  • In cultured cells, gene deletion of Bax/Bak or Bid abrogated apoptosis induced by overexpression of caspase-2. (elsevier.com)
  • Overexpression of bcl-2 proteins, due to a translocation of the gene, is associated with follicular lymphoma. (rush.edu)
  • Overexpression of Bcl-2 contributes to resistance of cancer cells to human cytotoxic lymphocytes (CL) by blocking granzyme B (GraB)-induced mitochondrial outer membrane permeabilization (MOMP). (isharonline.org)
  • Bcl-2 family member Bcl-G is not a proapoptotic protein. (nih.gov)
  • The expression of apoptosis regulators (proapoptotic protein Bad and anti-apoptotic protein Bcl-2) was analyzed and Bcl-2/Bad ratio in the follicular apparatus of the rat ovary was determined on day 3 after hyperthermia (rectal temperature 43.5°C). Hyperthermia in the catabolic phase leads to different degrees of activation of the molecular "switches" of apoptosis in cells of ovarian follicular epithelium. (springer.com)
  • In this study, we aimed at determining whether HGF is a potent inhibitor of cell apoptosis in NPC, and tried to find out which antiapoptotic or proapoptotic protein is involved in this process. (biomedsearch.com)
  • Bid, a widely expressed proapoptotic protein of the Bcl-2 family, disp. (ku.dk)
  • Bid is an abundant proapoptotic protein of the Bcl-2 family that is crucial for the induction of death receptor-mediated apoptosis in primary tissues such as liver. (ku.dk)
  • On the other hand, Bax, a proapoptotic protein, shows lower level in PD8 males than in PD8 females. (wikipedia.org)
  • J. Reed, C. Stein, S. Haldar, C. Subasinghe, C. Croce, S. Yum and J. Cohen, Antisense-mediated inhibition of Bcl-2 proto-oncogene expression and leukemic cell growth: Comparisons of phosphodiester and phosphorothioate oligodeoxynucleotides, Cancer Res . (springer.com)
  • Thus, E6 expression results in the loss of p53 function in cells, including stimulation of apoptosis and inhibition of the expression of the antiapoptotic protein bcl-2. (aacrjournals.org)
  • The molecular mechanism of the reversal in resistance may be attributed to the inhibition by ABT-263 of anti-apoptosis proteins of the Bcl-2 family. (springermedizin.de)
  • Hypoxic KRAS/PIK3CA -mutant HCT-116 and HCT-15 cell lines (both with low endogenous expression of the anti-apoptotic Mcl-1 protein and showing augmented inhibition of viability following the addition of ABT-737 to AZD8055) responded to combo-Rx by induction of apoptosis but with the simultaneous strong Mcl-1 up-regulation and activation of MAPK/PI3K-conducted signaling. (biomedcentral.com)
  • The concurrent inhibition of anti-apoptotic proteins and mTOR-mediated signaling in hypoxic KRAS/PIK3CA -mutant CRC cell lines resulted in pro-survival responses in parallel with the intended anti-proliferative effects, a finding that should be of note if considering combinatory targeting of multiple pathways in this CRC entity. (biomedcentral.com)
  • Guizhi Xiao, Hao Fang, Chengguo Xing and Wenfang Xu, " Structure, Function and Inhibition of Bcl-2 Family Proteins: A New Target for Anti-Tumor Agents", Mini-Reviews in Medicinal Chemistry (2009) 9: 1596. (eurekaselect.com)
  • The herpes simplex virus 1 (HSV-1) Us3 open-reading frame encodes a serine/threonine protein kinase that participates in the inhibition of apoptosis induced by virus infection and other stress agents. (semanticscholar.org)
  • Significant inhibition of apoptosis with increased expression of BIRC3 and Bcl-2 and enhanced activation of Akt/PKB was induced by protein S in islet β-cells compared with controls. (diabetesjournals.org)
  • It is proposed that vinblastine primes the cells for apoptosis by activating a pro-apoptotic Bcl-2 protein while concurrent inhibition of anti-apoptotic proteins leads to rapid apoptosis . (dartmouth.edu)
  • The rapid apoptosis is dependent on vinblastine-mediated activation of JNK which may cause concurrent inhibition of Bcl-2 . (dartmouth.edu)
  • One exception is the sensitization of NB4 cells to ABT-737 , a situation where JNK-mediated inhibition of Bcl-2 would be redundant . (dartmouth.edu)
  • We therefore examined whether miRNA-mediated inhibition of PUMA translation was responsible for the loss of PUMA protein. (uoguelph.ca)
  • We provide evidence for the role of miR-24-2 and miR-29a as mediators of this repression and that strategies directed at the inhibition of these miRNAs could be effective in sensitizing cells to heat-induced apoptosis. (uoguelph.ca)
  • See the other reference sequence protein isoform for the Bcl2l14 gene (NP_001342615.1). (nih.gov)
  • Apoptosis regulator BAX, also known as bcl-2-like protein 4, is a protein that in humans is encoded by the BAX gene. (wikipedia.org)
  • BAX is a member of the Bcl-2 gene family. (wikipedia.org)
  • The BAX gene was the first identified pro-apoptotic member of the Bcl-2 protein family. (wikipedia.org)
  • p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence. (uniprot.org)
  • Bcl-2 is a member of a large gene family encoding proteins that can either inhibit (e.g. (sigmaaldrich.com)
  • From a rat ovarian fusion cDNA library, we isolated a new pro-apoptotic Bcl-2 gene, Bcl-2-related ovarian killer (Bok). (pnas.org)
  • Recent studies demonstrated that another C. elegans gene, ced-4, or its mammalian homolog Apaf-1 can bridge between Bcl-2/ced-9 family members and caspases ( 7 , 8 ). (pnas.org)
  • Y. Tsujimoto, J. Cossman, E. Jaffe and C. Croce, Involvement of the Bcl-2 gene in human follicular lymphoma, Science 228: 1440 (1985). (springer.com)
  • The bcl-2 gene was identified at chromosomal translocation breakpoints in follicular lymphomas and contributes to tumorigenesis by inhibiting programmed cell death rather than by stimulating cell growth ( 1 , 59 ). (asm.org)
  • The mcl-1 gene encodes a 37-kDa protein with significant homology to Bcl-2, particularly in the carboxyl portion. (scielo.br)
  • Below are the list of possible Bcl-2-like gene 16 protein products. (mybiosource.com)
  • Characterization of a Herpes Simplex Virus 1 (HSV-1) Chimera in Which the Us3 Protein Kinase Gene Is Replaced with the HSV-2 Us3 Gene. (semanticscholar.org)
  • The protein encoded by this gene belongs to the BCL2 protein family. (nih.gov)
  • Plasmids containing a luciferase reporter gene under the control of this bcl-2 P1 promoter region, along with mutants to alter or eliminate G-quadruplex formation, were constructed in order to study the ability of Pu39 to control transcription. (arizona.edu)
  • Bcl-2 and related cytoplasmic proteins are key regulators of apoptosis, the cell suicide program critical for development, tissue homeostasis, and protection against pathogens. (sciencemag.org)
  • Proteins of the Bcl-2 family are critical regulators of apoptosis, but how its BH3-only members activate the essential effectors Bax and Bak remains controversial. (rupress.org)
  • B-cell lymphocyte/leukemia 2 (Bcl-2) family proteins are important regulators of apoptosis. (eurekaselect.com)
  • The proteins of the Bcl-2 family are important regulators of apoptosis, or programmed cell death. (inserm.fr)
  • Thus, Bcl-2 appears to be a more general inhibitor of cell death than previously appreciated. (sciencemag.org)
  • Following treatment with sirtinol (inhibitor of SIRT1), the expression of the pro-survival protein Bcl-2 was markedly decreased in both MCF-7 and MDA-MB-231 cell lines, particularly in MDA-MB-231. (nih.gov)
  • Unlike all other BCL-2 proteins, apo BFL-1 contains a surface-accessible cysteine within its BH3-binding groove, allowing for selective covalent targeting by a NOXA BH3-based stapled peptide inhibitor. (rcsb.org)
  • HGF is a potent inhibitor of cell apoptosis in NPC by upregulating Bcl-2 through both autocrine and paracrine EBV-independent pathways. (biomedsearch.com)
  • An antisense construct targeting Bcl-2 or a Bcl-2-specific inhibitor was able to sensitize resistant SCLC cells to RAD001. (aacrjournals.org)
  • In this study, we demonstrate that ABT-263, a potent and orally bioavailable inhibitor of the Bcl-2 family, was able to reverse the resistance of hepatocarcinoma cell lines to TRAIL-induced apoptosis, while sparing normal liver cells. (springermedizin.de)
  • Since CRC comprises heterogeneous tumors with predominant hypoxic components, we investigated effects of an inhibitor of anti-apoptotic Bcl-2 family proteins (ABT-737) in combination with an mTOR inhibitor (AZD8055)-collectively referred to as combo-Rx, in hypoxic CRC cell lines. (biomedcentral.com)
  • The present article updates the small molecules targeting proteins of the BCL-2 family with the discovery of not only highly potent antagonists of prosurvival members but also direct activators of the MOMP effectors BAX and BAK and a dual prosurvival inhibitor/proapoptotic activator. (immune-source.com)
  • Interestingly, sabutoclax has turned out to be a pan-BCL-2 inhibitor in some but not all cellular systems, displaying its best activity in inhibiting MCL-1 [26]. (immune-source.com)
  • We show that active caspase-2, but neither a catalytically mutated caspase-2 nor active caspase-2 with its inhibitor, can cause cytochrome c release. (elsevier.com)
  • It supports the neuroprotective action of activated protein C ( 10 ) and circulates in plasma as both free and in complex with C4b-binding protein (C4BP), which is an inhibitor of the classic complement pathway ( 11 ). (diabetesjournals.org)
  • ABT-737 , an inhibitor of Bcl-2 and Bcl-X , acutely sensitized only the NB4 cells which express only Bcl-2 . (dartmouth.edu)
  • Here, we show that wild-type Bcl-2 antiapoptotic proteins, but not Beclin 1 binding defective mutants of Bcl-2, inhibit Beclin 1-dependent autophagy in yeast and mammalian cells and that cardiac Bcl-2 transgenic expression inhibits autophagy in mouse heart muscle. (nih.gov)
  • Forced expression of Bcl-2 in cardiac muscle of transgenic mice decreased the number of autophagic structures that appeared in mice after 48 hours of starvation. (sciencemag.org)
  • In MCF7 cells (which do not have wild-type beclin 1), expression of mutant forms of beclin 1 that could not bind Bcl-2 caused an increase in basal, as well as starvation-induced, autophagic structures. (sciencemag.org)
  • Signaling pathways emanating from the endoplasmic reticulum (ER) are involved in apoptosis initiated by stimuli as diverse as ER stress, oncogene expression, death receptor (DR) ligation and oxidative stress, and the BCL-2 family is almost invariably implicated in the regulation of these pathways. (nature.com)
  • The expression of BAX is upregulated by the tumor suppressor protein p53, and BAX has been shown to be involved in p53-mediated apoptosis. (wikipedia.org)
  • This was seen from increased intensity of immunohistochemical staining for Bad protein against the background of more pronounced expression of Bcl-2 protein. (springer.com)
  • Is the Subject Area "Protein expression" applicable to this article? (plos.org)
  • Hepatocyte growth factor suppresses tumor cell apoptosis in nasopharyngeal carcinoma by upregulating Bcl-2 protein expression. (biomedsearch.com)
  • Expression of HGF, Bcl-2 and Bax in tumor tissues was investigated by immunohistochemical staining, and the apoptotic index was evaluated using the Terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL) method in all of the NPC cases. (biomedsearch.com)
  • NPC cells were treated with HGF (25 ng/ml), followed by an assay for cell viability and apoptosis, as well as by an expression analysis of Bcl-2 and Bax using immunostaining and Western blot. (biomedsearch.com)
  • Strong expression of HGF in tumor cells and stromal cells was significantly associated with decreased apoptotic index, advanced clinical stage, lymph node metastasis and high-expression of Bcl-2. (biomedsearch.com)
  • In vitro, exogenous HGF was found to promote cell growth, to suppress cell apoptosis and to upregulate the expression of Bcl-2 in NPC cells without EBV infection. (biomedsearch.com)
  • The expression of caspase‑3, Bax and Bcl‑2 genes was detected by the reverse transcriptase polymerase chain reaction (RT‑PCR). (spandidos-publications.com)
  • Nerve cell apoptosis may occur following cerebral ischemia or reperfusion injury as a result of the expression of apoptosis-related proteins and a complicated process leading to physiological and pathological alterations. (spandidos-publications.com)
  • Those studies also demonstrated that the expressed Bax activated caspase-3, indirectly inhibited Bcl-2 expression, formed Bax-Bcl-2 heterodimers and initiated cell apoptosis following cerebral ischemia/reperfusion injury. (spandidos-publications.com)
  • The present study investigated the expression of caspase-3, Bcl-2 and Bax and neuron apoptosis, as well as the ethological alterations following cerebral ischemia-reperfusion injury in a rat model. (spandidos-publications.com)
  • Recently, we found increased bcl-2 expression in cervical carcinoma cell lines containing mutated or E6-inactivated p53 (X. L. Liang, S. Mungal, A. Ayscue, J. D. Meissner, P. Wodnicki, G. Gordon, S. Lockett, and B. Herman. (aacrjournals.org)
  • Here, we compared the relative expression of BH3-only proteins in the spinal cord of end-stage G93A mutant SOD1 mice to age-matched wild-type (WT) mice. (frontiersin.org)
  • Finally, examination of protein expression using western blotting also revealed marked increases in DP5/Hrk and BNip3L in G93A mutant SOD1 lumbar spinal cord lysates compared to WT controls. (frontiersin.org)
  • The expression of P53, Bcl-2, Bax, Bag-1, and Mcl-1 proteins in CD5/CD20-positive B-chronic lymphocytic leukemia (B-CLL) cells from 30 typical CLL patients was evaluated before and after 48 h of incubation with 10 -6 M fludarabine using multiparametric flow cytometric analysis. (scielo.br)
  • Protein expression was correlated with annexin V expression, Rai modified clinical staging, lymphocyte doubling time, and previous treatment. (scielo.br)
  • B) BCL-2 expression levels in Jurkat and WEHI-231 clones, determined by Western blot analysis of lysates from equivalent cells of various Jurkat or WEHI-231 clones with anti-hBCL-2 Ab 6C8 and anti-β-actin Ab. (asm.org)
  • Intriguingly, we observed low Bcl-2 family proteins levels in the SCLC cells with a constitutive Akt pathway activation, whereas an increased expression was detected in the RAD001-resistant SCLC cells. (aacrjournals.org)
  • Importantly, the differences in SCLC cells' responsiveness to RAD001 are based on the activation status of the Akt/mTOR pathway and the expression levels of Bcl-2 family proteins. (aacrjournals.org)
  • Based on our findings, for a clinical relevant application it may be of advantage to screen SCLC patients for Akt/mTOR pathway activation status and Bcl-2 family expression prior to considering the use of RAD001 in combination with chemotherapeutic agents such as etoposide. (aacrjournals.org)
  • Expression profiles of p53, p21, bax and bcl-2 proteins in all-trans-retinoic acid treated primary and metastatic melanoma cells. (diva-portal.org)
  • The protein expression of p53, p21, bax and bcl-2 were examined by Western blotting and immunocytochemistry. (diva-portal.org)
  • Expression of p53, p21 and bax was increased, and bcl-2 was decreased in melanoma cells after exposure to atRA at different concentrations for various periods of time. (diva-portal.org)
  • we investigated the expression of molecules involved in muscle fibre death and survival mechanisms (Bcl-2, Fas, Fas-ligand and TRAIL), focusing on disorders with possible involvement of cytotoxic T cells. (diva-portal.org)
  • By using immunohistochemistry, Western blot and real-time PCR we detected a constitutional expression of Bcl-2 in healthy muscle, whereas the expression was weaker in disease processes. (diva-portal.org)
  • Methods -The expression of Bcl-2, Bcl-X L , and Mcl-1 was investigated in normal biliary epithelium (17), biliary dysplasia (three), and invasive cholangiocarcinoma (51), in addition to three human cholangiocarcinoma cell lines, by immunohistochemistry and immunofluorescence. (bmj.com)
  • Results -The expression of Bcl-2 was not detected in normal or malignant biliary tissue. (bmj.com)
  • 22- 24 Studies involving a variety of haematological and several solid malignancies have identified a correlation between high Bcl-2 or Bcl-X L expression, poor patient response to treatment, and overall prognosis. (bmj.com)
  • Expression of Bcl-2 family proteins and associated clinicopathologic factors predict survival outcome in patients with oral squamous cell carcinoma. (semanticscholar.org)
  • The aims of this study were to assess the expression levels of three proteins involved in apoptosis--Bcl-2, Bcl-X, and Bax--and evaluate their relationship with clinicopathologic features and survival in oral squamous cell carcinoma (OSCC). (semanticscholar.org)
  • Immunohistochemistry was used to evaluate protein expression in 53 primary OSCCs treated by radical surgery with free margins at a single institution in 1999. (semanticscholar.org)
  • Cell viability measures, expression of proteins implicated in apoptosis and MAPK/PI3K-AKT/mTOR pathway signaling, and profiling of composite kinase activities were undertaken in a panel of 14 cell lines. (biomedcentral.com)
  • Bcl-2 expression was as follows: chronic gastritis 0%, atrophic gastritis 35% (23/65 cases), intestinal metaplasia 90% (45/50 cases), dysplasia 100% (40/40 cases), intestinal type adenocarcinoma 83.3% (25/30 cases), and diffuse type adenocarcinoma 70% (14/20 cases). (openarchives.gr)
  • Monoclonal antibodies were generated against the human BAD protein and used to evaluate its expression by immunoblotting and immunohistochemistry in normal human tissues and by immunoblot analysis of the National Cancer Institute anti-cancer drug screening panel of 60 human tumor cell lines. (elsevier.com)
  • Immunostaining of tissues revealed many examples of cell-type-specific expression of BAD, suggesting dynamic regulation of BAD protein levels in vivo. (elsevier.com)
  • The relative levels of BAD protein varied widely among established human tumor cell lines, with colon, lung, and melanomas generally having the highest expression. (elsevier.com)
  • Taken together, these findings define for the first time the normal cell-type-specific patterns of expression and intracellular locations of the BAD protein in vivo and provide insights into the regulation of this pro-apoptotic Bcl-2 family protein in human tumors. (elsevier.com)
  • Reed, John C. / Expression and location of pro-apoptotic bcl-2 family protein BAD in normal human tissues and tumor cell lines . (elsevier.com)
  • Antisense nucleotide sequences (oligonucleotides) targeted at BCL-2 messenger RNA reduces the expression of BCL-2 and increases apoptosis in these tumours with clinical improvement. (thefreedictionary.com)
  • CD44 and Bcl-2 expression was detected in 86% and 82% of breast tumours, respectively. (aacrjournals.org)
  • There was no significant correlation between CD44+ tumour cell prevalence and tumour characteristics, whereas the prevalence of CD44+ cells was associated with higher levels of Bcl-2 expression ( P = 0.004). (aacrjournals.org)
  • Our findings suggest that the prevalence of CD44+ tumour cells as a subpopulation of breast cancer stem cells was of no clinicopathological significance, but was correlated with higher Bcl-2 expression. (aacrjournals.org)
  • The resistance of CSCs to chemotherapy may be caused through increased expression of the Bcl-2 family proteins, which leads to increased expression of membrane proteins responsible for drug resistance. (aacrjournals.org)
  • DZNep represses Bcl-2 expression and modulates apoptosis sensitivity in response to Nutlin-3a. (rush.edu)
  • The qRT-PCR and western blot analyses revealed that both the mRNA and protein expression of significantly increased with the establishment of the PF pool at 3 dpp and was retained at a higher level from 5 dpp to 7 dpp, during which PF activation was generally initiated (Fig?1b, c). (monossabios.com)
  • c Western blot assay showed that E-cad protein expression was increasing from 1 dpp to 7 dpp. (monossabios.com)
  • As we identified with AML cell outlines, sensitivity to help ABT-199 linked directly together with BCL-2 manifestation and inversely with BCL-XL expression because measured simply by quantitative Traditional western blot (Figure 4D-E). Absolutely no significant romantic relationship was seen between MCL-1 level in addition to sensitivity that will ABT-199 throughout primary AML myeloblasts (Supplemental Figure S6). (biogeology.org)
  • Initial luciferase assay results in HeLa and HEK293 cells suggest that mutants designed to isolate certain G-quadruplex structures caused an overall decrease in protein expression while mutants designed to knock out major folding structures caused an increase in protein expression. (arizona.edu)
  • Selectively induces apoptosis and downregulates Bcl-XL protein expression in various human cancer cells versus normal cells in vitro . (apexbt.com)
  • The efficacy of many chemotherapeutic agents can be attenuated by expression of the anti-apoptotic proteins Bcl-2 , Bcl-X and Mcl-1 . (dartmouth.edu)
  • Because flavopiridol-mediated sensitization did not correlate with expression of Mcl-1 , these results suggest another short-lived protein suppresses this acute apoptosis . (dartmouth.edu)
  • Interestingly , OCI-AML1 cells were acutely sensitive to vinblastine alone , which was attributed to their expression of only Bcl-2 and at very low levels . (dartmouth.edu)
  • To investigate the functional role of bcl-2 protein in the process of differentiation of oral keratinocytes, bcl-2 expression vector was transfected into SCC-25 cells, which normally undergo squamous cell differentiation in vitro while expressing specific differentiation markers, e.g., keratin 10/11 and involucrin. (elsevier.com)
  • In bcl-2 transfected SCC-25 cells, the expression of these differentiation markers was markedly suppressed. (elsevier.com)
  • The anti-apoptotic protein, Bcl-2, interacts with the evolutionarily conserved autophagy protein, Beclin 1. (nih.gov)
  • Although they demonstrated si-p53 or si-p21 affect Bcl-w:Bax interaction, they did not prove endogenous p53 interacts with p21. (aacrjournals.org)
  • Homodimerization of Bcl-2 with itself involves a head-to-tail interaction, in which an N-terminal domain where BH4 resides interacts with the more distal region of Bcl-2 where BH1, BH2, and BH3 are located. (springer.com)
  • Bag-1 was first cloned from mouse cells as a novel protein which interacts with Bcl-2 and Bcl-X L , enhancing the ability of Bcl-2 to prevent apoptosis. (scielo.br)
  • E-cad can be thought as a single-pass transmembrane proteins that interacts with -catenin by its cytodomain and attaches towards the actin cytoskeleton20. (monossabios.com)
  • Bcl-2 interacts with tBid (Yi et al. (reactome.org)
  • This protein is reported to interact with, and increase the opening of, the mitochondrial voltage-dependent anion channel (VDAC), which leads to the loss in membrane potential and the release of cytochrome c. (wikipedia.org)
  • Shimizu, S., Narita, M. and Tsujimoto T, Y Bcl-2 family proteins regulate the release of apoptogenic cytochrome c by the mitochondrial channel VDAC. (springer.com)
  • In this study, we used both in vitro mitochondrial cytochrome c release assays and cell culture apoptosis analyses to investigate the mechanism by which caspase-2 induces apoptosis. (elsevier.com)
  • now show that Bcl-2 also inhibits autophagy through its interactions with beclin 1. (sciencemag.org)
  • Interactions of endogenous proteins p53 and p21 in IMR-32 neuroblastoma and H460 lung cancer cells. (aacrjournals.org)
  • Direct interactions between BCL‐2 family members are essential for the proper regulation and implementation of apoptosis during development and for homoeostasis. (els.net)
  • Commitment of cells to apoptosis is governed largely by protein-protein interactions between members of the Bcl-2 protein family. (nih.gov)
  • Once activated, they were thought to bind promiscuously to pro-survival protein targets but unexpected selectivity has recently emerged from analysis of their interactions. (nih.gov)
  • Regardless of this, a detailed understanding of the interactions between family members, which are often selective, has notable implications for designing anti-cancer drugs to target the Bcl-2 family. (nih.gov)
  • A combination of the solution studies together with a new application of DCA to the eukaryotic proteins NAF-1 and Bcl-2 provided sufficient constraints at amino acid resolution to predict the interaction surfaces and orientation of the protein-protein interactions involved in the docked structure. (sigmaaldrich.com)
  • To gain better understanding of how this protein functions, we have undertaken a structure-function analysis of this protein, focusing on domains within Bcl-2 that are required for function and for interactions with other proteins. (springer.com)
  • The emerging picture is that of an intricate cellular machinery orchestrated by tightly regulated molecular interactions and conformational changes within BCL-2 family proteins that ultimately govern the cellular commitment to apoptotic death. (aacrjournals.org)
  • Initiators such as caspase-8 and caspase-9 are apical caspases that are activated on binding to specialized molecular platforms that are assembled through selective protein-protein interactions. (aacrjournals.org)
  • The molecular platforms in charge of initiator caspase activation are formed through interactions involving distinct protein folds or binding cassettes, of which three have been structurally characterized: death domains, death effector domains, and caspase recruitment domains ( 13 ). (aacrjournals.org)
  • A) Interactions between Bcl-2 family members show the rationale of our experiments. (rupress.org)
  • Molecular basis for Bcl-2 homology 3 domain recognition in the Bcl-2 protein family: identification of conserved hot spot interactions. (inserm.fr)
  • The results identified amino acids of both the anti-apoptotic proteins as well as the Bcl-2 homology 3 (BH3) domains of the pro-apoptotic proteins that make strong, recurrent interactions in the protein complexes. (inserm.fr)
  • And while this model has been repeatedly exemplified in vitro, the e↵ect of membranes on Bcl-2 protein interactions has not yet been fully explored in living cells. (uni-tuebingen.de)
  • BCL-2 , the first family member, forms the molecular basis for sustaining the lymphoma cancer cells. (britannica.com)
  • The interaction between beclin 1 and Bcl-2 was confirmed in HT-29 cells overexpressing Bcl-2 by coimmmunoprecipitation, and beclin 1 was identified on endoplasmic and mitochondrial membranes (the locations of Bcl-2) based on cell fractionation and confocal microscopy. (sciencemag.org)
  • In HT-29 cells overexpressing Bcl-2, the formation of the beclin and hVps34 complex, which has class III phosphoinositide 3-kinase (PI3K) activity, was inhibited, as was the colocalization of beclin 1 with PI3P (phosphatidylinositol 3-phosphate), suggesting that Bcl-2 inhibited the PI3K activity of the beclin 1-hVSP34 complex. (sciencemag.org)
  • In HeLa cells, which endogenously express both beclin 1 and Bcl-2, Bcl-2 and beclin 1 coimmunoprecipitated under nutrient-rich conditions, and this interaction was decreased when the cells were starved of nutrients. (sciencemag.org)
  • Knockdown of Bcl-2 in HeLa cells with siRNA resulted in an increase in the number of autophagic structures under starvation conditions compared with those observed in starved cells with wild-type levels of Bcl-2. (sciencemag.org)
  • For instance, binding of HA-BAD to BCL-xL and concomitant disruption of BAX:BCL-xL interaction was found to partly reverse paclitaxel resistance in human ovarian cancer cells. (wikipedia.org)
  • The retrotranslocation of BCL-2 proteins from the OMM can be measured using fluorescence-labeled protein in intact cells or endogenous protein from isolated heavy membrane fractions. (springer.com)
  • Some cancer cells, such as melanoma, overexpress Bcl-2 preventing apoptosis and allowing malignant growth to continue. (sigmaaldrich.com)
  • As they requested, we have presented coimmunoprecipitation data showing endogenous p53-p21 protein interaction in IMR-32 and H460 cells ( Fig. 1 ). (aacrjournals.org)
  • BCL‐2 was the first cloned component of the mechanism for apoptosis - the process by which metazoan cells commit suicide - to be recognized. (els.net)
  • According to this model, apoptosis can be triggered by increasing the concentration of BH3‐only proteins, adding an artificial BCL‐2 antagonist, or depleting the cells of antiapoptotic BCL‐2 family members. (els.net)
  • In healthy (non‐apoptotic) cells, only small amounts of antiapoptotic BCL ‐2 members need to be bound to BAX and BAK at any one time. (els.net)
  • Interaction of overexpressed p53 and p21 proteins in p53-null H1299 cells correlated with decreased cell invasion. (aacrjournals.org)
  • On day 3 after exposure to hyperthermia, Bcl-2/Bad ratio increased, which reflects antiapoptotic protection of cells and conditions for blockade of mitochondrial pathway of apoptosis in the follicular apparatus of the ovaries during the acute period after hyperthermia. (springer.com)
  • There is some evidence that Bcl-2 pro-survival proteins (which normally keep cells alive by inhibiting the cell death program of apoptosis) are expressed at unusually high levels in melanoma compared to normal melanocytes. (edu.au)
  • Deletion of the BH1, BH2, or BH4 domains of Bcl-2 abolishes its ability to suppress cell death in mammalian cells and prevents homodimerization of these mutant proteins, though these mutants can still bind to the wild-type Bcl-2 protein. (springer.com)
  • KSBcl-2, encoded by the Kaposi's sarcoma-associated herpesvirus, was the only viral Bcl-2 homolog that was capable of killing cells when expressed as an N-terminal truncation. (asm.org)
  • Our main goal was to determine the predictive value of these proteins in CLL cells in terms of disease evolution. (scielo.br)
  • In most patients, the circulating mature B-lymphocytes are largely quiescent G 0 phase cells, which accumulate due to longer survival than normal B cells rather than to increased proliferation (2). (scielo.br)
  • At least 15 Bcl-2 family members have been identified in mammalian cells and several others in viruses. (acris-antibodies.com)
  • Numerous studies have demonstrated that over-expressing anti-apoptotic Bcl-2 proteins is one mechanism for cancer cells to acquire resistance against cancer chemotherapies, suggesting antagonizing these proteins would be a potential approach to overcoming such drug resistance. (eurekaselect.com)
  • BCL-2 was immunoprecipitated from 32 P-orthophosphate-labeled Jurkat-BCL-2 cells treated with paclitaxel (+) or DMSO (−) by using anti-hBCL-2 Ab 6C8, separated by SDS-PAGE, and transferred to a nitrocellulose membrane. (asm.org)
  • The residual-shifted band on Western analysis of Jurkat cells bearing AA/A or Neo represents the endogenous hBCL-2 of Jurkat cells. (asm.org)
  • Moreover, it has been shown that polypeptide growth factors such as stem cell factor (SCF) and fibroblast growth factor-2 (FGF-2) induce a variety of responses in human SCLC cells, including growth and proliferation, chemoresistance, and motility ( 3 - 6 ). (aacrjournals.org)
  • Furthermore, it has been found that the ribosomal protein S6 kinases-1 and -2 (S6K1, 2) are highly overexpressed in SCLC cells compared with normal human type II pneumocytes, and that mTOR transduces mitogen-induced proliferation in SCLC ( 6 ). (aacrjournals.org)
  • In this study, we used a similar cell culture model system of matched primary and metastatic melanoma cells from the same patient to investigate whether p53 and bcl-2 family proteins were involved in atRA-induced apoptosis. (diva-portal.org)
  • These data indicate that p53, p21, bax and bcl-2 proteins were involved in atRA-induced apoptosis in melanoma cells. (diva-portal.org)
  • Modification of these protein levels in the tumour cells might be beneficial for early treatment of melanoma. (diva-portal.org)
  • In contrast, granular cytoplasmic Bcl-X L and Mcl-1 staining was found in 60-100% of cells in all normal, dysplastic, and malignant specimens, including the human cell lines examined in this study. (bmj.com)
  • Conclusion -These findings indicate that Mcl-1 and Bcl-X L , but not Bcl-2, are involved in the survival of normal and neoplastic cells in the biliary tree. (bmj.com)
  • High concentrations of Bcl-2 or Bcl-X L affect the susceptibility of a cell to the induction of apoptosis by altering the ratio of death promoters to suppressors, providing tumour cells with a survival advantage, and permitting expansion of transformed cells harbouring mutations within their genome. (bmj.com)
  • Finally, the viability of cancer cells transfected with a plasmid containing HBx (hepatitis B virus X protein) following treatment with TRAIL was also measured. (springermedizin.de)
  • The pseudorabies virus US3 protein kinase possesses anti-apoptotic activity that protects cells from apoptosis during infection and after treatment with sorbitol or staurosporine. (semanticscholar.org)
  • However, a recent careful analysis has demonstrated that TW-37 (i) induces several typical features of mitochondrial apoptosis in MCL-1-dependent cells [but not BCL-2 or BCL-XL-dependent cells] and (ii) exhibits all the hallmarks of a NOXA-like BH3 mimetic antagonizing selectively MCL-1, although only at high concentrations [26]. (immune-source.com)
  • COLD SPRING HARBOR, N.Y. (Nov. 2, 2010) - One million cells in our bodies die every second - they commit suicide by a mechanism known as apoptosis. (cshlpress.org)
  • Prof. Green has made fundamental contributions to our understanding of activation-induced apoptosis in T cells, the role of the oncogene Myc in driving apoptosis, the ability of BCL-2 proteins to block cell death, the functions of death receptors in cell death and the immune system, and the mitochondrial pathway of apoptosis-publishing over 400 papers along the way. (cshlpress.org)
  • A 25 kDa inner mitochondrial membrane protein which inhibits apoptosis, thus increasing the survival of cells (good or bad). (thefreedictionary.com)
  • These cells can resist apoptosis through mechanisms such as the regulation of Bcl-2. (aacrjournals.org)
  • One hundred and forty-six primary operable breast cancer patients were investigated in order to identify the population of CD44+ and Bcl-2+ cells in paraffin-embedded tissues by immunohistochemistry. (aacrjournals.org)
  • Indeed, only cancer stem cells (CSCs) or tumour-initiating cells can repopulate the bulk of a tumour in the long term so as to maintain its ability of renewing continuously, thereby mimicking their normal counterparts albeit abnormally ( 2 , 3 ). (aacrjournals.org)
  • It has been proven that stem cells can resist apoptosis through a variety of mechanisms, including the regulation of Bcl-2, whereas non-tumourigenic cells in tumours are more susceptible to the induction of apoptosis or chemotherapy ( 7 - 9 ). (aacrjournals.org)
  • Caspase-2 is an initiating caspase required for stress-induced apoptosis in various human cancer cells. (elsevier.com)
  • However, it is not clear how caspase-2 exerts its apoptotic function in cells and whether its enzymatic activity is required for the apoptotic function. (elsevier.com)
  • Consistent with this we found that ABT-737 effectively restored MOMP in Bcl-2 overexpressing cells treated with GraB or natural killer cells. (isharonline.org)
  • Background Extracellular vesicles (EVs) are secreted from many cells, carrying cargoes including proteins and nucleic acids. (techxprtz.com)
  • After 2 h adherence at 37C, cells had been cleaned and treated with different concentrations of newly ready serotonin (Sigma Chemical substance Co., St Louis, MO, USA) for 2 h just before being activated with suboptimal focus of lipopolysaccharide (LPS) ( 005. (colinsbraincancer.com)
  • G) Fluorescence strength profiles assessed at three different period factors (1, 2 and 5 times of differentiation) for cells pursuing transects as proven clearly uncovered the difference between nuclear and cytoplasmic fluorescence. (yearoftheturtle.org)
  • Open up in another window Body 2 Immunohistochemical staining with two commercially obtainable anti-BCMA antibodies present disparate staining within the mind(A) IHC staining of little intestine displaying plasma cells using B0807-50G (dark brown staining) and AF193 (magenta staining). (yearoftheturtle.org)
  • Likewise, cytokine creation in response to BCMA was saturated in the chosen clones 4, 10, 13 and 15 weighed against small to no antigen-induced cytokine for UTD or clone 9 CAR cells (Supplementary Body 2). (yearoftheturtle.org)
  • This study shows that protein S attenuates diabetes by inhibiting apoptosis of β-cells and the development of diabetic nephropathy. (diabetesjournals.org)
  • Apoptosis of β-cells caused by glucotoxicity, lipotoxicity, advanced glycation end products, inflammatory cytokines, and intracellular deposition of islet amyloid polypeptide are believed to be the cause of the reduced number of islet β-cells in type 2 diabetes ( 5 ). (diabetesjournals.org)
  • Therefore, apoptosis of β-cells is a mechanistic pathway common to both type 1 and type 2 diabetes. (diabetesjournals.org)
  • The method includes increasing the activity of Bcl-2 in cells affected by the disease or pathological condition. (google.com)
  • The method includes increasing the activity of Bcl-2 in a population of cells and transplanting the population of cells having increased Bcl-2 activity into a subject. (google.com)
  • A method to enhance the sensitivity of malignant cells to therapy is provided that includes decreasing the activity of Bcl-2 in the malignant cells. (google.com)
  • However , most leukemia cells appear to rely on Bcl-2 or Bcl-X rather than Mcl-1 to protect themselves from this acute vinblastine-mediated apoptosis . (dartmouth.edu)
  • However , GX15-070 , which inhibits Mcl-1 , Bcl-2 and Bcl-X only sensitized the ML-1 cells . (dartmouth.edu)
  • The level of Bcl-2 in PD8 male rats is much higher than that in female rats of the same age, hence the number of apoptotic cells of MPNc in PD8 male rats is much lower than PD8 female rats. (wikipedia.org)
  • In addition to the regulation of apoptosis, BCL-2 proteins at the ER also regulate autophagy, a survival pathway that limits metabolic stress, genomic instability and tumorigenesis. (nature.com)
  • Bcl-2-related proteins act upstream from caspases in the cell death pathway ( 6 ). (pnas.org)
  • The Bcl-2 protein blocks a distal step in an evolutionarily conserved pathway for programmed cell death and apoptosis. (springer.com)
  • Apoptosis is a conserved genetic and biochemical pathway whose basic tenets are present in all metazoans ( 1 , 2 ). (aacrjournals.org)
  • This review is limited in scope to the intrinsic pathway and its regulation by BCL-2 family of proteins. (aacrjournals.org)
  • We propose to call this the `Bcl-2 regulated pathway', because the Bcl-2 family of proteins are critical regulators of this process ( Adams and Cory, 2001 ). (biologists.org)
  • This review focuses on the `Bcl-2-regulated pathway', particularly on the role of the BH3-only proteins in the apoptosis signalling cascade. (biologists.org)
  • Proteins of the BCL-2 family control the mitochondrial pathway of apoptosis. (immune-source.com)
  • In the other, Roy have presented a comprehensive review of compounds that target the BCL-2 family-driven pathway [16]. (immune-source.com)
  • The molecular interaction between tumor suppressor p53 and the anti-apoptotic Bcl-2 family proteins plays an essential role in the transcription-independent apoptotic pathway of p53. (ntu.edu.sg)
  • Taken altogether, our results revealed a structural basis for a conserved binding mechanism between p53DBD and the anti-apoptotic Bcl-2 family proteins, which shed light on to the molecular understanding of the transcription-independent apoptosis pathway of p53. (ntu.edu.sg)
  • Collectively, these results indicate that proteolytic activation of Bid and the subsequent induction of the mitochondrial apoptotic pathway through Bax/Bak is essential for apoptosis triggered by caspase-2. (elsevier.com)
  • Conditions that disrupt the luminal environment and these core ER functions, including oxidative stress, perturbation of Ca 2+ or energy stores and accumulation of unfolded/misfolded proteins result in an evolutionarily conserved adaptive response termed the UPR. (nature.com)
  • The indirect activation model suggests that they simply must neutralize all of the prosurvival Bcl-2 family members, whereas the direct activation model proposes that Bim and Bid must activate Bax and Bak directly. (rupress.org)
  • In this model, the prosurvival Bcl-2 family members hold subpopulations of Bax and Bak molecules in check until BH3-only proteins free them. (rupress.org)
  • The preclinical and clinical properties of the small molecules inhibiting prosurvival BCL-2 family proteins have been extensively reviewed [5-16]. (immune-source.com)
  • Boxed sequences indicate the 26-mer peptides used to measure the affinities of the mutant BH3 peptides for mouse Bcl-x L , Mcl-1, and Bax. (rupress.org)
  • Tryptic peptides derived from bands 1, 2, and 3 were also eluted from the radioactive spots on TLC plates (A, C, and E) and subjected to phosphoamino acid analysis, confirming their composition. (asm.org)
  • To elucidate the molecular basis of this recognition process, we used molecular dynamics simulations coupled with the Molecular Mechanics/Poisson-Boltzmann Surface Area approach to identify the amino acids that make significant energetic contributions to the binding free energy of four complexes formed between Bcl-xl and pro-apoptotic Bcl-2 homology 3 peptides. (inserm.fr)
  • Those most similar to Bcl-2 promote cell survival by inhibiting adapters needed for activation of the proteases (caspases) that dismantle the cell. (sciencemag.org)
  • To determine if viral Bcl-2 proteins can be converted into death factors, similar to their cellular counterparts, five herpesvirus Bcl-2 homologs from five different viruses were tested for their susceptibility to caspases. (asm.org)
  • However, because KSBcl-2 was not cleavable by caspases, the latent proapoptotic activity of KSBcl-2 apparently cannot be released. (asm.org)
  • Thus, herpesvirus Bcl-2 homologs escape negative regulation by retaining their antiapoptotic activities and/or failing to be converted into proapoptotic proteins by caspases during programmed cell death. (asm.org)
  • The function of cellular Bcl-2 family members is regulated in part by caspases. (asm.org)
  • They become activated through proteolysis by already active caspases or through autocatalytic processing, which is mediated by aggregation of zymogens in a complex containing adapter proteins (e.g. (biologists.org)
  • Thus, Bcl-2 not only functions as an antiapoptotic protein, but also as an antiautophagy protein via its inhibitory interaction with Beclin 1. (nih.gov)
  • Using a yeast autophagy reconstitution assay and two transfected mammalian cell systems, Bcl-2 was found to inhibit beclin 1-mediated formation of autophagic structures through a mechanism that required the functional binding sites mediating the interaction between these two proteins. (sciencemag.org)
  • No coimmunoprecipitation experiments documenting endogenous p53:p21 protein interaction were performed. (aacrjournals.org)
  • In contrast, Bcl-2/Bax heterodimerization involves a tail-to-tail interaction, that requires the portion of Bcl-2 where BH1, BH2, and BH3 reside and a central region in Bax where the BH3 domain is located. (springer.com)
  • Specific Aim 1 will test the hypothesis that Bcl-2/Bcl-xL phosphorylation regulates protein:protein interaction, in particular the binding/release of pro-apoptotic Bcl-2 proteins and especially activator and/or sensitizer BH3-only proteins. (grantome.com)
  • Here we describe a mutation in mouse and human Bak that specifically disrupts its interaction with the prosurvival protein Bcl-xL Substitution of Glu75 in mBak (hBAK Q77) for leucine does not affect the three-dimensional structure of Bak or killing activity but reduces its affinity for Bcl-xL via loss of a single hydrogen bond. (rcsb.org)
  • The p53 protein is a transcription factor that, when activated as part of the cell's response to stress, regulates many downstream target genes, including BAX. (wikipedia.org)
  • Mammals are now known to carry genes for a large number of BCL‐2 like proteins, some of which, like BCL‐2 itself, inhibit apoptosis, and others that promote or are required for apoptosis. (els.net)
  • Abnormalities to the regulation of cell death, such as those caused by mutations to genes for BCL‐2 family members prevent apoptosis occurring when it should, and can lead to diseases including cancer. (els.net)
  • Abnormalities to the regulation of this cell death process, including mutations to genes for BCL‐2 family members, can lead to a disease, such as cancer. (els.net)
  • Rapid acclimation of juvenile corals to CO2-mediated acidification by upregulation of heat shock protein and Bcl-2 genes. (coralcoe.org.au)
  • This protein forms a heterodimer with BCL2, and functions as an apoptotic activator. (wikipedia.org)
  • Several isoforms of BCL2-associated X protein occur due to ALTERNATIVE SPLICING of the mRNA for this protein. (harvard.edu)
  • Group I Bcl-2 proteins can form heterodimers with group II and prevent the occurrence of programmed cell death (5). (scielo.br)
  • These proteins regulate this fundamental biological process via the formation of heterodimers involving both pro- and anti-apoptotic family members. (inserm.fr)
  • Bcl-xl, an anti-apoptotic protein of this family, is known to form heterodimers with multiple pro-apoptotic proteins, such as Bad, Bim, Bak, and Bid. (inserm.fr)
  • Forms homodimers, and heterodimers with BAX , BAD , BAK and Bcl-X(L). Heterodimerization with BAX requires intact BH1 and BH2 motifs, and is necessary for anti-apoptotic activity (By similarity). (sdsc.edu)
  • A BCL-2-like protein that has a C-terminal BCL-2 homology (BH3) domain and forms heterodimers with other BCL-2 FAMILY PROTEINS. (ouhsc.edu)
  • A major finding of our article is that the p53/p21 complex is a functional unit that can act on multiple cellular components and that prosurvival Bcl-2 proteins are targets of the p53/p21 complex. (aacrjournals.org)
  • BCL-2 family proteins regulate MOMP and thereby determine the cellular commitment to apoptosis. (aacrjournals.org)
  • However, unlike the caspase cleavage products of cellular Bcl-2, Bcl-x L , and Bid, which are potent inducers of apoptosis, the cleavage product of γHV68 Bcl-2 lacked proapoptotic activity. (asm.org)
  • More than 15 cellular Bcl-2-related proteins have been identified in a wide range of species. (asm.org)
  • The E6 oncoprotein forms a complex with the cellular tumor suppressor protein p53, leading to degradation of p53 via ubiquitin-dependent proteolysis. (aacrjournals.org)
  • This family of opposing cell survival and cell death proteins regulates pathways associated with apoptotic and non-apoptotic forms of cell death, as well as cellular macroautophagy - all of which are critical for both normal development and various pathologies, including many forms of cancer. (mcgill.ca)
  • We discovered that culturing AML cellular lines or even primary tissues in the lack of serum with regard to 8 they would did not affect the mitochondrial priming or BCL-2 dependence, when compared with culture within the presence regarding serum (Supplemental Figure S4). (biogeology.org)
  • Remarkably, although N1 shows no sequence similarity to cellular proteins, its three-dimensional structure closely resembles Bcl-x(L) and other members of the Bcl-2 protein family. (ox.ac.uk)
  • Thus, we provide the first definitive in vivo evidence that prosurvival proteins maintain cellular viability by interacting with and inhibiting Bak. (rcsb.org)
  • In support of this finding virally expressed N1 co-precipitated with endogenous pro-apoptotic Bcl-2 proteins Bid, Bad and Bax as well as with Bad and Bax expressed by transfection. (ox.ac.uk)
  • The protooncogene Bcl-2 was isolated at the breakpoint of the t(14, 18) chromosomal translocation associated with follicular B-cell lymphoma ( 9 ). (pnas.org)
  • The cardinal member of this family, BCL-2, was originally discovered as the defining oncogene in follicular lymphomas, located at one reciprocal breakpoint of the t(14;18) (q32;q21) chromosomal translocation. (aacrjournals.org)
  • Bcl-2 was first described in follicular lymphomas with t(14;18) translocation (4). (scielo.br)
  • Bcl-2 is over expressed in follicular lymphomas with the translocation t(14;18)(q32;q21), detected in 70 to 95% of follicular lymphomas and 20% of diffuse large B cell lymphomas. (thefreedictionary.com)
  • Association to the apoptosis repressors Bcl-X(L), BHRF1, Bcl-2 or its adenovirus homolog E1B 19k protein suppresses this death-promoting activity. (rcsb.org)
  • Silent mating-type information regulation 2 homologue 1 (SIRT1), a member of the class III histone deacetylase (HDAC) family, is the mammalian ortholog of yeast Sir2. (nih.gov)
  • The specific integrated approach described in this paper provides the first structural information, to our knowledge, for future targeting of the NAF-1-Bcl-2 complex in the regulation of apoptosis/autophagy in cancer biology. (sigmaaldrich.com)
  • J.C. Reed, Bcl-2 and the regulation of programmed cell death, J. Cell Biol . (springer.com)
  • Tsujimoto, Y. and Shimizu, S. VDAC regulation by the Bcl-2 family of proteins. (springer.com)
  • The finding that members of one of the major protein families involved in cell death regulation also aberrantly regulated in cancers, the Bcl-2 family of proteins, are also critical mediators of metabolic pathways, provides strong evidence for the importance of the metabolic shift to cancer cell survival. (biomedcentral.com)
  • Using this mutant, we investigated the requirement for physical restraint of Bak by Bcl-xL in apoptotic regulation. (rcsb.org)
  • The ER lumen represents both the major site of intracellular Ca 2+ storage and the site at which transmembrane and secreted proteins are folded and post-translationally modified. (nature.com)
  • In the protein's inactive form, the groove binds its transmembrane domain, transitioning it from a membrane-bound to a cytosolic protein. (wikipedia.org)
  • Most BCL‐2 family members also have a hydrophobic region at the carboxy‐terminus (grey) that can act as a transmembrane domain. (els.net)
  • Bok had conserved Bcl-2 homology (BH) domains 1, 2, and 3 and a C-terminal transmembrane region present in other Bcl-2 proteins, but lacked the BH4 domain found only in anti-apoptotic Bcl-2 proteins. (pnas.org)
  • Rabbit polyclonal to Transmembrane protein 57 methods. (colinsbraincancer.com)
  • Furthermore, Beclin 1 mutants that cannot bind to Bcl-2 induce more autophagy than wild-type Beclin 1 and, unlike wild-type Beclin 1, promote cell death. (nih.gov)
  • They spontaneously adopt a 'ready' conformation (BH3 'fingers' exposed), which allows them to bind to BCL‐2, MCL1 or BCLX (blue), but doing so promotes their reversion into the inactive state (BH3 not exposed). (els.net)
  • BH3‐only proteins (green) can bind to BCL‐2, MCL1 and BCLX , preventing them from inactivating BAX and BAK . (els.net)
  • Some BH3-only proteins also bind to Bax and Bak. (nih.gov)
  • These mutants also fail to bind to BAG-1 and Raf-1, two proteins that we have shown can associate with protein complexes containing Bcl-2 and which cooperate with Bcl-2 to suppress cell death. (springer.com)
  • Further, NMR chemical shift perturbation data showed that Bcl-w and Mcl-1 bind to the positively charged DNA-binding surface of p53DBD. (ntu.edu.sg)
  • The structure also reveals that N1 has a constitutively open surface groove similar to the grooves of other anti-apoptotic Bcl-2 proteins, which bind the BH3 motifs of pro-apoptotic Bcl-2 family members. (ox.ac.uk)
  • All tested herpesvirus Bcl-2 homologs possess antiapoptotic activity, including the more distantly related homologs encoded by murine gammaherpesvirus 68 (γHV68) and bovine herpesvirus 4 (BHV4), as described here. (asm.org)
  • Substitution of phosphorylation sites in BCL-2 further enhances antiapoptotic activity. (asm.org)
  • Kim and colleagues reported a p53/p21 complex regulates cancer cell invasion and apoptosis by targeting the Bcl-2 family ( 1 ). (aacrjournals.org)
  • The Bcl-2 family of proteins regulates mitochondrial outer membrane permeabilization (MOMP) - considered as the point-of-no-return in apoptosis. (uni-tuebingen.de)
  • Protein S is an anticoagulant factor that also regulates inflammation and cell apoptosis. (diabetesjournals.org)
  • Identification of Bok as a new pro-apoptotic Bcl-2 protein with restricted tissue distribution and heterodimerization properties could facilitate elucidation of apoptosis mechanisms in reproductive tissues undergoing hormone-regulated cyclic cell turnover. (pnas.org)
  • Subsequent studies identified a family of Bcl-2-related proteins possessing several conserved Bcl-2 homology (BH) domains important for homo- or heterodimerization between family members ( 11 - 13 ). (pnas.org)
  • Through heterodimerization, the balance between pro- and anti-apoptotic Bcl-2 proteins presumably determines the cell fate ( 3 , 13 ). (pnas.org)
  • Taken together, the data suggest the possibility that both Bcl-2/Bcl-2 homodimerization and Bcl-2/Bax heterodimerization are necessary but insufficient for the anti-apoptotic function of the Bcl-2 protein. (springer.com)
  • A member of the Bcl-2 protein family and homologous partner of C-BCL-2 PROTO-ONCOGENE PROTEIN. (harvard.edu)
  • Proto-Oncogene Proteins c-bcl-2" is a descriptor in the National Library of Medicine's controlled vocabulary thesaurus, MeSH (Medical Subject Headings) . (rush.edu)
  • This graph shows the total number of publications written about "Proto-Oncogene Proteins c-bcl-2" by people in this website by year, and whether "Proto-Oncogene Proteins c-bcl-2" was a major or minor topic of these publications. (rush.edu)
  • Below are the most recent publications written about "Proto-Oncogene Proteins c-bcl-2" by people in Profiles. (rush.edu)
  • The bcl-2 proto-oncogene may play a critical role in opposing the commitment to terminal differentiation and apoptosis of oral keratinocytes. (elsevier.com)
  • Detection of Bcl-2 family member Bcl-G in mouse tissues using new monoclonal antibodies. (nih.gov)
  • Custom ELISA Kits, Recombinant Proteins and Antibodies can be designed, manufactured and produced according to the researcher's specifications. (mybiosource.com)
  • Whether Bax and Bak are activated directly by these BH3-only proteins, or indirectly as a consequence of BH3-only proteins neutralizing their pro-survival targets is the subject of intense debate. (nih.gov)
  • Integrated strategy reveals the protein interface between cancer targets Bcl-2 and NAF-1. (sigmaaldrich.com)
  • BCL-2 family proteins are high-priority cancer targets whose structures provide essential blueprints for drug design. (rcsb.org)
  • I will provide an overview of the functions of this family of proteins and their targets, and will discuss a possible molecular approach for the prevention of neurodegenerative diseases. (springer.com)
  • This protein family, which provides the framework for controlling apoptosis, takes its name from a type of cancer called B-cell lymphoma. (britannica.com)
  • This antiautophagy function of Bcl-2 may help maintain autophagy at levels that are compatible with cell survival, rather than cell death. (nih.gov)
  • This cell death was inhibited by knockdown of the autophagy protein ATG5 by RNAi. (sciencemag.org)
  • BCL-2 proteins control stress-dependent commitment to the programmed cell death apoptosis. (springer.com)
  • Mol Cell Oncol 2:e995029. (springer.com)
  • The ratio of Bcl-2 to Bax in the cell can determine whether or not the cell initiates apoptosis or survives. (sigmaaldrich.com)
  • We found that p21 knockdown with or without cytoplasmic p53 (p53 K305N ) did not significantly influence cell growth in serum-free and 10% FBS-containing media ( Fig. 2 ), suggesting that p21 can regulate cell invasion without significantly altering cell growth. (aacrjournals.org)
  • This nuclear function of p53 is distinguished from the function of cytoplasmic p53, which suppresses cell invasion by liberating Bax from prosurvival Bcl-2 proteins ( 6 ). (aacrjournals.org)
  • BCL‐2 family proteins interact with each other to regulate and implement the cell death programme. (els.net)
  • This is important as tumor cell growth and proliferation is required for invasiveness ( 2 ). (aacrjournals.org)
  • This will be achieved through the use of Bcl-2 protein-selective reagents, which were engineered in the Fairlie laboratory, to profile melanoma cell lines, as well as samples from patients. (edu.au)
  • In the intracellular death program, hetero- and homodimerization of different anti- and pro-apoptotic Bcl-2-related proteins are critical in the determination of cell fate. (pnas.org)
  • Cell killing induced by Bok was also suppressed following coexpression with Mcl-1 and BHRF1 but not with Bcl-2, further indicating that Bok heterodimerized only with selective anti-apoptotic Bcl-2 proteins. (pnas.org)
  • A growing body of evidence suggests that the intracellular "death program" activated during apoptosis is similar in different cell types and conserved during evolution ( 1 , 2 ). (pnas.org)
  • Involved in these decisions are protein complexes that assimilate a variety of inputs that report on the status of the cell and lead to an output response. (sigmaaldrich.com)
  • Thus, Bcl-2 may suppress cell death at least in part by binding to Bax via the BH3 domain and thereby preventing formation of Bax/Bax homodimers. (springer.com)
  • Further studies however are required to delineate the full significance of Bcl-2/Bcl-2, Bcl-2/Bax, and Bax/Bax dimers and the biochemical mechanisms by which Bcl-2 family proteins ultimately control cell life and death. (springer.com)
  • A hundred and forty-seven cases of NPC and CNE-1, CNE-2 NPC cell line were collected. (biomedsearch.com)
  • The Bcl-2 homologs encoded by herpesvirus saimiri, Epstein-Barr virus, and BHV4 were not cleaved by apoptotic cell extracts and did not possess latent proapoptotic activities. (asm.org)
  • The Bcl-2 family of proteins is a major cell death regulator and is implicated in determining the survival or death of neurons under physiological as well as pathological conditions. (springer.com)
  • Tsujimoto, Y Prevention of neuronal cell death by Bcl-2. (springer.com)
  • The molecular pathogenesis of HPV was analyzed by correlating the data with the expressions of different cell cycle associated molecules such as p53, bcl-2 and PCNA in the biopsy. (abebooks.com)
  • ii)HPV infection establishes its carcinogenicity through altered cell cycle control molecules such as p53, bcl-2 and PCNA iii)Retinoid ATRA level has a major role during carcinogenesis and it was found to be associated with the oncopotency of HPV types. (abebooks.com)
  • The BH3-only members of the Bcl-2 protein family are essential initiators of programmed cell death and are required for apoptosis induced by cytotoxic stimuli. (biologists.org)
  • These proteins have evolved to recognise distinct forms of cell stress. (biologists.org)
  • Proteins of Bcl-2(B-cell lymphoma-2) family are key regulators of programmed cell death. (eurekaselect.com)
  • The BAD protein is a pro-apoptotic member of the Bcl-2 family whose ability to heterodimerize with survival proteins such as Bcl-X(L) and to promote cell death is inhibited by phosphorylation. (elsevier.com)
  • His current research focuses on mitochondrial physiology in cell survival and cell death, the functions of the BCL-2 family, and other aspects of cell death. (cshlpress.org)
  • The proteins are found on mitochondrial, microsomal, and NUCLEAR MEMBRANE sites within many cell types. (rush.edu)
  • Demolished sciences will Rather have free in your bcl 2 protein family essential regulators of cell of the apologies you Are changed. (shebeen-news.de)
  • Cell viability Dynorphin A (1-13) Acetate IC50 (93 2%) was dependant on Trypan blue exclusion. (colinsbraincancer.com)
  • AMs, NR8383, had been pretreated with serotonin for 2 h activated or not really with LPS (1 ng/ml) for 20 h and IL-10 discharge was assessed in cell-free supernatants. (colinsbraincancer.com)
  • Alveolar macrophages (AMs) had been treated for 2 h with different concentrations of serotonin (10?11?10?9 M) before getting activated or not with lipopolysaccharide (LPS) for 20 h and cell-free supernatants had been tested for IL-10 content material (a). (colinsbraincancer.com)
  • AMs had been treated with serotonin for 2 h, activated with bacille CalmetteCGurin (BCG) for 20 h or with LPS for 4 h, and IL-12 (b) and TNF (c) discharge were assessed in cell-free supernatants, respectively. (colinsbraincancer.com)
  • Furthermore, E-cad plays roles in signal transduction from the cytomembrane to nucleus via -catenin, which is not only a transcriptional co-activator but also a well-accepted binding protein of E-cad in cell adhesion22. (monossabios.com)
  • bcl-2 protein in non-small-cell lung carcinoma. (ox.ac.uk)
  • Exogenous protein S improved insulin sensitivity in adipocytes, skeletal muscle, and liver cell lines in db/db mice compared with controls. (diabetesjournals.org)
  • Type 2 diabetes is associated with insulin resistance and abnormal insulin secretion, with evidence suggesting that reduced β-cell mass is linked to dysfunctional insulin secretion ( 3 , 5 ). (diabetesjournals.org)
  • In vivo, loss of Bcl-xL binding to Bak led to significant defects in T-cell and blood platelet survival. (rcsb.org)
  • Plants expressing human Bcl-2 and Bcl-xl, nematode CED-9, or baculovirus Op-IAP transgenes conferred heritable resistance to several necrotrophic fungal pathogens, suggesting that disease development required host-cell death pathways. (pnas.org)
  • In the yeast two-hybrid system, Bok interacted strongly with some (Mcl-1, BHRF1, and Bfl-1) but not other (Bcl-2, Bcl-xL, and Bcl-w) anti-apoptotic members. (pnas.org)
  • CCAAT displacement proteins/homolog (CDP/do it again sequences. (techxprtz.com)
  • Finally, we have developed a triple-transgenic mouse model (3xTg-AD) that overexpress the antiapoptotic protein, Bcl-2, in all postmitotic neurons of the CNS. (pubmedcentralcanada.ca)
  • This study compared the development of diabetes between wild-type and transgenic mice overexpressing human protein S and the development of diabetic glomerulosclerosis between mice treated with and without human protein S and between wild-type and protein S transgenic mice. (diabetesjournals.org)
  • Diabetic wild-type mice treated with protein S and diabetic protein S transgenic mice developed significantly less severe diabetic glomerulosclerosis than controls. (diabetesjournals.org)
  • Transgenic tobacco harboring Bcl-xl with a loss-of-function mutation did not protect against pathogen challenge. (pnas.org)
  • Ubiquitin-like protein MNSFβ covalently binds to Bcl-G and enhances lipopolysaccharide/interferon γ-induced apoptosis in macrophages. (nih.gov)
  • A hydrophobic groove formed along the C-terminal of α2 to the N-terminal of α5, and some residues from α8, binds the BH3 domain of other BAX or BCL-2 proteins in its active form. (wikipedia.org)
  • NAF-1 is a homodimeric member of the novel Fe-S protein NEET family, which binds two 2Fe-2S clusters. (sigmaaldrich.com)
  • NAF-1 binds to both the pro- and antiapoptotic regions (BH3 and BH4) of Bcl-2, as demonstrated by a nested protein fragment analysis in a peptide array and DXMS analysis. (sigmaaldrich.com)
  • Bad binds Bcl-2, Bcl-x L , and Bcl-w, whereas Noxa binds only Mcl-1 and A1. (rupress.org)
  • TW-37, a rationally designed benzoylsulphonyl analog of gossypol [22, 27], was also known to operate only in part as a pan-BH3 mimetic: it binds to BCL-2, BCL-XL and MCL-1 with moderate affinity (sub-M), induces apoptosis depending partially on BAX/BAK activation and shows several off-target effects. (immune-source.com)
  • Two of the most recent reviews have described the biological context to targeting these proteins and advances in therapeutic approaches with BH3 mimetics. (immune-source.com)
  • These data bring a new dimension to the therapeutic targeting of BCL-2 family proteins. (immune-source.com)
  • Our lab studies various aspects of this complex and unique biology, including the modulation of Bcl-2 family activity for potential therapeutic benefit in cancer. (mcgill.ca)
  • In the present review, we focused on the recent developments in therapeutic targeting of different steps in glycolysis, glutaminolysis and on the metabolic regulatory role of Bcl-2 family proteins. (biomedcentral.com)
  • Lauterwasser J., Fimm-Todt F., Edlich F. (2019) Assessment of Dynamic BCL-2 Protein Shuttling Between Outer Mitochondrial Membrane and Cytosol. (springer.com)
  • Paclitaxel induces phosphorylation of Ser70, Ser87, and Thr69 in BCL-2 (A) 2D mapping and synthetic phosphopeptide comigration study of band 1. (asm.org)
  • The Us3 protein kinase of herpes simplex virus 1 blocks apoptosis and induces phosporylation of the Bcl-2 family member Bad. (semanticscholar.org)
  • More distant relatives instead promote apoptosis, apparently through mechanisms that include displacing the adapters from the pro-survival proteins. (sciencemag.org)
  • Its three sub-families have distinct roles: the BH3-only proteins trigger apoptosis by binding via their BH3 domain to pro-survival relatives, while the pro-apoptotic Bax and Bak have an essential downstream role involving disruption of organellar membranes and induction of caspase activation. (nih.gov)
  • Our hypothesis is that Bcl-2 pro-survival proteins provide a survival advantage for melanomas and might contribute to resistance to standard chemotherapeutic drugs. (edu.au)
  • Our research aims to identify the key Bcl-2 pro-survival proteins that are responsible for melanoma survival. (edu.au)
  • The second aim is to determine whether resistance to current melanoma treatment arises due to elevated levels of Bcl-2 pro-survival proteins, and whether treatment with Bcl-2-targeting molecules will resensitise tumours to standard drugs, informing potential drug treatment combinations. (edu.au)
  • Most pro-survival members, which can inhibit apoptosis in the face of a wide variety of cytotoxic insults, contain at least BH1 and BH2, and those most similar to Bcl-2 have all four BH domains. (acris-antibodies.com)
  • These "BH3 domain" proteins may well represent the physiological antagonists of the pro-survival proteins. (acris-antibodies.com)
  • By prolonging survival through blocking apoptosis, these proteins might be reducing the efficacy of cytotoxic anticancer treatments in cholangiocarcinoma. (bmj.com)
  • The BAD protein derived from 11 of 41 tumor lines that expressed this pro-apoptotic protein migrated in gels as a clear doublet, consistent with the presence of hyperphosphorylated BAD protein. (elsevier.com)
  • Recent studies suggest that it can mediate the death function of tumor suppressor p53 and is activated by a multimeric protein complex, PIDDosome. (elsevier.com)
  • Bcl-2 Proteins in Mechanism of Anti-mitotic Drug Action Narrative: Anti-tumor drugs are widely used in cancer treatment. (grantome.com)
  • p53 and p21 may form complexes with many other proteins. (aacrjournals.org)
  • There was no consideration of how the p53/p21/Bcl-w complex might relate to p53/MDM2 or p21/cyclin/CDK/PCNA complexes. (aacrjournals.org)
  • Noticeably, the refined structural models of the complexes between p53DBD and Bcl-w, Mcl-1, and Bcl-2 showed that the binding mode of p53DBD is highly conserved among the anti-apoptotic Bcl-2 family proteins. (ntu.edu.sg)
  • At least in vitro , Mcl-1 has functions similar to those of Bcl-2, having the ability to heterodimerize with Bax and to neutralize Bax-mediated cytotoxicity (6). (scielo.br)
  • Artificial BCL‐2 antagonists, such as ABT‐263 (light blue) can act like BH3‐only proteins by binding to antiapoptotic BCL‐2 family proteins. (els.net)
  • Antagonists Against Anti-Apoptotic Bcl-2 Family Proteins for Cancer Treatment. (eurekaselect.com)
  • Jignesh M. Doshi and Chengguo Xing, " Antagonists Against Anti-Apoptotic Bcl-2 Family Proteins for Cancer Treatment. (eurekaselect.com)
  • After 3 GDC-0834 times in vitro (DIV), pieces had been used in serum-free medium comprising 98% Neurobasal-A and 2% B-27 (Thermofisher Scientific, Waltham, MA, USA), supplemented with 2 mM Glutamax, 28 mM d-glucose, 100 U/mL penicillin/streptomycin and 25 mM HEPES. (yearoftheturtle.org)
  • A) The mobility shift of BCL-2 induced by paclitaxel is due to phosphorylation. (asm.org)
  • A) Jurkat clones and WEHI-231 clones stably expressing WT or alanine-substituted phosphorylation sites of BCL-2, consisting of Ser70 (S70A), Ser87 (S87A), or all three phosphorylation sites, including Thr69 plus the two serines (AA/A), or an empty vector (Neo) were generated. (asm.org)
  • In the previous funding cycle, studies were undertaken to test our main hypothesis, that Bcl-2/Bcl-xL phosphorylation is a key event controlling apoptosis induction by anti-mitotic drugs and is catalyzed by a novel or unsuspected kinase. (grantome.com)
  • We were successful in largely completing the aims and validating our hypothesis, and excitingly, obtained evidence implicating CDK1/cyclin B as the kinase responsible for MIA-induced Bcl-2/Bcl-xL phosphorylation. (grantome.com)
  • The results provide compelling evidence that CDK1-mediated Bcl-2/Bcl-xL phosphorylation acts as a functional link coupling mitotic arrest and apoptosis, and suggest the possibility that anti-apoptotic Bcl-2 proteins act as sensors for CDK1 signal duration. (grantome.com)
  • In Specific Aim 2, we will examine the role of Mcl-1 phosphorylation in MIA-induced apoptosis, based on preliminary data that CDK1 mediates Mcl-1 degradation. (grantome.com)
  • Aim: Our aim was to evaluate the role of Bax and Bcl-2 apoptosis- related proteins in the carcinogenesis of the stomach. (openarchives.gr)