bcl-2-Associated X Protein: 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.Trans-Activators: Diffusible gene products that act on homologous or heterologous molecules of viral or cellular DNA to regulate the expression of proteins.Hepatitis B virus: 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.Hepatitis B Antigens: 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.Carcinoma, Hepatocellular: 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.Liver Neoplasms: Tumors or cancer of the LIVER.Proto-Oncogene Proteins c-bcl-2: 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.Bornaviridae: 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.Hepatocytes: The main structural component of the LIVER. They are specialized EPITHELIAL CELLS that are organized into interconnected plates called lobules.Transcriptional Activation: Processes that stimulate the GENETIC TRANSCRIPTION of a gene or set of genes.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Hep G2 Cells: A human liver tumor cell line used to study a variety of liver-specific metabolic functions.Apoptosis: 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.Transfection: 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.Fragile X Mental Retardation Protein: 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.Hepatitis B Virus, Woodchuck: An ORTHOHEPADNAVIRUS causing chronic liver disease and hepatocellular carcinoma in woodchucks. It closely resembles the human hepatitis B virus.Gene Expression Regulation, Viral: Any of the processes by which cytoplasmic factors influence the differential control of gene action in viruses.DNA-Binding Proteins: 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.Hepatitis B: 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.Marmota: A genus of Sciuridae consisting of 14 species. They are shortlegged, burrowing rodents which hibernate in winter.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Transcription, Genetic: The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.Molecular Sequence Data: 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.Borna disease virus: 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.Cell Line, Tumor: A cell line derived from cultured tumor cells.Hepadnaviridae: 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).Promoter Regions, Genetic: 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.Chloramphenicol O-Acetyltransferase: 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.Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.X Chromosome: 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.Tumor Suppressor Protein p53: 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.Mutation: 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.Protein Binding: 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.Liver: A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.Group X Phospholipases A2: 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.Blotting, Western: 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.Plasmids: 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, Messenger: 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.Signal Transduction: 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.Viral Regulatory and Accessory Proteins: 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.Tumor Cells, Cultured: 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.NF-kappa B: 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.Virus Replication: 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.Mice, Transgenic: Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.Amino Acid Sequence: 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.Precipitin Tests: 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.Gene Expression Regulation: 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.Mitochondria: 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)Proto-Oncogene Proteins: 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.Genes, bcl-2: 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.Viral Proteins: Proteins found in any species of virus.Cell Nucleus: 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)Hepatitis B, Chronic: 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.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.Reverse Transcriptase Polymerase Chain Reaction: 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.Genes, Viral: The functional hereditary units of VIRUSES.Hepatitis B Core Antigens: The hepatitis B antigen within the core of the Dane particle, the infectious hepatitis virion.Proteasome Endopeptidase Complex: 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.bcl-X Protein: 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.Cell Proliferation: All of the processes involved in increasing CELL NUMBER including CELL DIVISION.Up-Regulation: 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.Hepatocyte Nuclear Factor 1: 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.Down-Regulation: 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.Nuclear 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.RNA, Small Interfering: 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.CARD Signaling Adaptor Proteins: 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.Two-Hybrid System Techniques: 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.DNA, Viral: Deoxyribonucleic acid that makes up the genetic material of viruses.Translocation, Genetic: A type of chromosome aberration characterized by CHROMOSOME BREAKAGE and transfer of the broken-off portion to another location, often to a different chromosome.Cell Survival: 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.Gene Expression Regulation, Neoplastic: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in neoplastic tissue.RNA Interference: 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.Lymphoma, B-Cell: A group of heterogeneous lymphoid tumors generally expressing one or more B-cell antigens or representing malignant transformations of B-lymphocytes.Caspase 3: 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.Caspases: 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.Enhancer Elements, Genetic: Cis-acting DNA sequences which can increase transcription of genes. Enhancers can usually function in either orientation and at various distances from a promoter.Fragile X Syndrome: 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)Chromosomes, Human, Pair 14: A specific pair of GROUP D CHROMOSOMES of the human chromosome classification.Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.HeLa Cells: 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, Reporter: 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.Phosphorylation: 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: Hepatocyte nuclear factor 1-alpha is a transcription factor found in the LIVER; PANCREAS; and KIDNEY that regulates HOMEOSTASIS of GLUCOSE.Lymphoma, Large B-Cell, Diffuse: 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.Luciferases: 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.BH3 Interacting Domain Death Agonist Protein: A member of the Bcl-2 protein family that reversibly binds MEMBRANES. It is a pro-apoptotic protein that is activated by caspase cleavage.Germinal Center: 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 Fusion Proteins: 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.Mice, Inbred C57BLDNA, Complementary: 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.Cyclic AMP Response Element-Binding Protein: 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.Chromosomes, Human, Pair 18: A specific pair of GROUP E CHROMOSOMES of the human chromosome classification.Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.Factor X: 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.Polymerase Chain Reaction: 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.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Real-Time Polymerase Chain Reaction: Methods used for detecting the amplified DNA products from the polymerase chain reaction as they accumulate instead of at the end of the reaction.Cloning, Molecular: 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.DNA Primers: 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.Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes.Cell Transformation, Neoplastic: 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.Cell Line, Transformed: 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.Cysteine Endopeptidases: 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.Dietary Proteins: Proteins obtained from foods. They are the main source of the ESSENTIAL AMINO ACIDS.Flow Cytometry: 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.Gene Expression Profiling: The determination of the pattern of genes expressed at the level of GENETIC TRANSCRIPTION, under specific circumstances or in a specific cell.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Cell Cycle: 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, Cultured: 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.Restriction Mapping: Use of restriction endonucleases to analyze and generate a physical map of genomes, genes, or other segments of DNA.Multienzyme Complexes: 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.Cytoplasm: 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)Protein Structure, Tertiary: 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.Genome, Viral: The complete genetic complement contained in a DNA or RNA molecule in a virus.Sequence Homology, Amino Acid: The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.Mice, Knockout: 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.Protein-Serine-Threonine Kinases: A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.Simian virus 40: A species of POLYOMAVIRUS originally isolated from Rhesus monkey kidney tissue. It produces malignancy in human and newborn hamster kidney cell cultures.Kinetics: The rate dynamics in chemical or physical systems.Mice, Inbred BALB CRNA-Binding Proteins: Proteins that bind to RNA molecules. Included here are RIBONUCLEOPROTEINS and other proteins whose function is to bind specifically to RNA.Drosophila Proteins: 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.Mice, Nude: 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.Protein Biosynthesis: The biosynthesis of PEPTIDES and PROTEINS on RIBOSOMES, directed by MESSENGER RNA, via TRANSFER RNA that is charged with standard proteinogenic AMINO ACIDS.Disease Models, Animal: 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.Repetitive Sequences, Nucleic Acid: 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).Enzyme Activation: 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.Models, Biological: 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.Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability.Adaptor Proteins, Signal Transducing: 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 enzymesCell Division: The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.Neoplasm Proteins: 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.Lymphoma, Follicular: 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.PhosphoproteinsRepressor Proteins: 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.RNA, Viral: Ribonucleic acid that makes up the genetic material of viruses.B-Lymphocytes: 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.Gene Rearrangement: The ordered rearrangement of gene regions by DNA recombination such as that which occurs normally during development.gamma-Globins: 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.In Situ Hybridization, Fluorescence: 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.Retinoid X Receptors: 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.Lymphoma, B-Cell, Marginal Zone: 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.Chromosomes, Human, Pair 3: A specific pair of human chromosomes in group A (CHROMOSOMES, HUMAN, 1-3) of the human chromosome classification.Myeloid Cell Leukemia Sequence 1 Protein: 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, Immunoglobulin Heavy Chain: 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).Precursor Cells, B-Lymphoid: 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.Leukemia, B-Cell: A malignant disease of the B-LYMPHOCYTES in the bone marrow and/or blood.NitrophenolsImmunoglobulin Heavy Chains: 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.Proto-Oncogenes: 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.Bacteriophage phi X 174: 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.Genes, myc: 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.Reticulocytosis: 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.Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.Precursor Cells, T-Lymphoid: Lymphocyte progenitor cells that are restricted in their differentiation potential to the T lymphocyte lineage.Neprilysin: 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.Leukemia, Lymphocytic, Chronic, B-Cell: 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.Receptors, Purinergic P2: 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.Fetal Hemoglobin: 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.Sperm Midpiece: The middle piece of the spermatozoon is a highly organized segment consisting of MITOCHONDRIA, the outer dense fibers and the core microtubular structure.Tumor Suppressor Proteins: 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.Cyclin D2: 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.Proto-Oncogene Proteins c-myc: 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.Chromosome Breakage: A type of chromosomal aberration involving DNA BREAKS. Chromosome breakage can result in CHROMOSOMAL TRANSLOCATION; CHROMOSOME INVERSION; or SEQUENCE DELETION.Gene Rearrangement, B-Lymphocyte: 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.Caspases, Effector: 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.Oligonucleotide Array Sequence Analysis: 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.Interferon Regulatory Factors: 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.Chromosomes, Human, Pair 11: A specific pair of GROUP C CHROMOSOMES of the human chromosome classification.Biphenyl CompoundsPrognosis: 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.Tumor Markers, Biological: 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.Chromosomal Puffs: Regions along polytene chromosomes that are uncondensed and active in DNA REPLICATION or RNA transcription (GENETIC TRANSCRIPTION).Immunophenotyping: 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.Factor X Deficiency: 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.Nuclear Receptor Co-Repressor 2: 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, Monoclonal, Murine-Derived: Antibodies obtained from a single clone of cells grown in mice or rats.HEK293 Cells: A cell line generated from human embryonic kidney cells that were transformed with human adenovirus type 5.Jurkat Cells: 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, Immunoglobulin: 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).Gene Rearrangement, B-Lymphocyte, Heavy Chain: 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.Phenotype: The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.delta-Globins: 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.I-kappa B Kinase: 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.Oncogene Proteins, Fusion: The GENETIC TRANSLATION products of the fusion between an ONCOGENE and another gene. The latter may be of viral or cellular origin.Lymphoma: A general term for various neoplastic diseases of the lymphoid tissue.Membrane Proteins: 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.Lymphoma, Non-Hodgkin: 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.Precursor T-Cell Lymphoblastic Leukemia-Lymphoma: 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.bcl-2 Homologous Antagonist-Killer Protein: 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, Neoplasm: DNA present in neoplastic tissue.beta-Globins: 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.Sulfonamides: A group of compounds that contain the structure SO2NH2.Polymorphism, Single Nucleotide: A single nucleotide variation in a genetic sequence that occurs at appreciable frequency in the population.Oncogenes: 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.Chromatin Immunoprecipitation: 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.Caspase 7: 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.T-Lymphocytes: 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.Zinc Fingers: 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.Receptors, CXCR5: CXCR receptors isolated initially from BURKITT LYMPHOMA cells. CXCR5 receptors are expressed on mature, recirculating B-LYMPHOCYTES and are specific for CHEMOKINE CXCL13.Antineoplastic Agents: Substances that inhibit or prevent the proliferation of NEOPLASMS.

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 ...
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. ...
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 ...
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 ...
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/
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.
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 ...
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.
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( ...
The Bcl-2 family of proteins is characterized by its ability to modulate cell death (apoptosis) under a broad range of physiological conditions.…
Bak小鼠单克隆抗体[AT8B4](ab104124)可与小鼠, 人样本反应并经WB, ELISA, ICC/IF实验严格验证。中国75%以上现货,所有产品提供质保服务,可通过电话、电邮或微信获得本地专属技术支持。
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 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 ...
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 ...
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.
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 ...
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 ...
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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Albany, New York, Dec 1, 2017: Apoptosis Regulator BAX (Bcl 2 Like Protein 4 or BCL2L4 or BAX) - Apoptosis regulator BAX or bcl-2-like protein 4 is a protein is encoded by the BAX gene. It accelerates programmed cell death by antagonizing the apoptosis repressor BCL2. It promotes activation of CASP3, and thereby apoptosis. It undergoes a conformation change that causes translocation to the mitochondrion membrane, leading to the release of cytochrome c that then triggers apoptosis under stress conditions.. Request For Free Sample - https://www.marketresearchhub.com/enquiry.php?type=S&repid=1389111. Apoptosis Regulator BAX (Bcl 2 Like Protein 4 or BCL2L4 or BAX) pipeline Target constitutes close to 7 molecules. Out of which approximately 3 molecules are developed by companies and remaining by the universities/institutes. The molecules developed by companies in Phase III, Phase II and Preclinical stages are 1, 1 and 1 respectively. Similarly, the universities portfolio in Preclinical and Discovery ...
Another mechanism by which the UPR could impact on cell death is the IRE1α pathway. Bak/Bax were suggested to directly interact with IRE1α resulting in activation of JNK (Hetz et al., 2006). However, neither the knockout of IRE1α, JNK nor other components of this pathway or JNK inhibition conferred protection from ER stress. Our observation that death of ire1α-/- cells was caspase dependent, whereas it was caspase independent in bak/bax-/- cells, rather suggests that Bak/Bax and IRE1α are acting on separate pathways.. In WT and Bak/Bax-deficient MEFs ER stress rapidly induced autophagic alterations. This indicates that autophagic alterations per se are independent of proapoptotic Bcl-2 proteins. Autophagy has been implied as a death mechanism substituting for deficient apoptosis under certain conditions (Levine and Yuan, 2005; Maiuri et al., 2007). Interestingly, autophagy was more pronounced in bak/bax-/- than in WT cells, as judged by an increased occurrence of autophagic vacuoles and ...
The effect of Bcl-xL upon the developmental death of T cells was assessed by generating transgenic mice that expressed Bcl-xL within all thymocyte subsets. Bcl-xL protected thymocytes from a variety of apoptotic stimuli, including gamma irradiation, glucocorticoids, and anti-CD3 treatment. Bcl-xL altered thymocyte maturation, resulting in increased numbers of CD3int/hi and CD4-8+ thymocytes. Overall, the phenotype of Bcl-xL transgenics was essentially indistinguishable from a Bcl-2 transgenic model. Overexpression of Bcl-xL or Bcl-2 resulted in the down-regulation of the other molecule, providing further evidence of their reciprocal regulation. In a genetic test of redundancy, the Bcl-xL transgene rescued mature T cells in Bcl-2 null mice. Immunoprecipitation indicated that Bcl-xL, like Bcl-2, heterodimerized with the death-promoting molecule Bax in thymocytes. This in vivo model argues that Bcl-xL, like Bcl-2, functions in a common pathway to repress cell death. ...
Research over the years has expanded the list of proteins structurally or functionally linked to BCL-2 (B-cell lymphoma-2), the product of a proto-oncogene identified almost thirty years ago. Discovery of the BCL-2 gene defined a new class of proto-oncogenes that block cell death without enhancing cell proliferation. Today, this protein group is formed by a family of BCL-2 homologs (which have phylogenetic relationships), and by a collection of evolutionarily and structurally unrelated proteins characterized by the presence of a region of local sequence similarity with BCL-2, termed the BH3 motif. BCL-2 homologous proteins share a similar α-helical bundle fold (the BCL-2 domain), have up to four different BH motifs (BH1-BH4), and can be either anti-apoptotic (e.g., BCL-2 and BCL-xL) or pro-apoptotic (e.g., BAX, BAK and BID). All the other (non-BCL-2 homologous) proteins possessing a functional BH3 motif are pro-apoptotic (such as the BH3-only member BIM or the BH3 motif-containing protein ...
Research over the years has expanded the list of proteins structurally or functionally linked to BCL-2 (B-cell lymphoma-2), the product of a proto-oncogene identified almost thirty years ago. Discovery of the BCL-2 gene defined a new class of proto-oncogenes that block cell death without enhancing cell proliferation. Today, this protein group is formed by a family of BCL-2 homologs (which have phylogenetic relationships), and by a collection of evolutionarily and structurally unrelated proteins characterized by the presence of a region of local sequence similarity with BCL-2, termed the BH3 motif. BCL-2 homologous proteins share a similar α-helical bundle fold (the BCL-2 domain), have up to four different BH motifs (BH1-BH4), and can be either anti-apoptotic (e.g., BCL-2 and BCL-xL) or pro-apoptotic (e.g., BAX, BAK and BID). All the other (non-BCL-2 homologous) proteins possessing a functional BH3 motif are pro-apoptotic (such as the BH3-only member BIM or the BH3 motif-containing protein ...
Mimicking the BH3 domain to kill cancers is a strategy that is presently being explored in the development of Bcl2 inhibitors as anticancer drugs (40, 41). By binding to the hydrophobic cleft of Bcl2/Bcl-XL, the BH3 mimetics function as competitive inhibitors (18, 40). Three small-molecule Bcl2 inhibitors, including gossypol (AT-101), obatoclax (GX15-070), and ABT-263, are in clinical trials (phase I∼II; refs. 40, 41). Gossypol and obatoclax are BH3 mimetics that act as pan-Bcl2 inhibitors (12, 41). However, gossypol and obatoclax are not entirely dependent on Bax and Bak for apoptosis induction and toxicity to normal cells (40, 42). In contrast, the Bad BH3 mimetic ABT-737 was ineffective in inducing apoptosis in cells doubly deficient in Bax and Bak, indicating that its mechanism of action may be predominantly through the Bcl2 family (40, 43). ABT-737 selectively binds to Bcl2, Bcl-XL, and Bcl-W but not Mcl-1 and Bfl-1/A1 (18). However, ABT-737 resistance can be caused by expression of Mcl-1 ...
The human lymphocyte toxins granzyme B (hGrzB) and perforin cooperatively induce apoptosis of virus-infected or transformed cells: perforin pores enable entry of the serine protease hGrzB into the cytosol, where it processes Bid to selectively activate the intrinsic apoptosis pathway. Truncated Bid (tBid) induces Bax/Bak-dependent mitochondrial outer membrane permeability and the release of cytochrome c and Smac/Diablo. To identify cellular proteins that regulate perforin/hGrzB-mediated Bid cleavage and subsequent apoptosis, we performed a gene-knockdown (KD) screen using a lentiviral pool of short hairpin RNAs embedded within a miR30 backbone (shRNAmiR ...
Mitochondria have emerged recently as effective targets for novel anti-cancer drugs referred to as mitocans. We propose that the molecular mechanism of induction of apoptosis by mitocans, as exemplified by the drug a-tocopheryl succinate, involves generation of reactive oxygen species (ROS). ROS then mediate the formation of disufide bridges between cytosolic Bax monomers, resulting in the formation of mitochondrial outer membrane channels. ROS also cause oxidation of cardiolipin, triggering the release of cytochrome c and its translocation via the activated Bax channels. This model may provide a general mechanism for the action of inducers of apoptosis and anticancer drugs, mitocans, targeting mitochondria via ROS production ...
We have shown for the first time that BCL-3 promotes the growth of colorectal cancer cells through activation of the AKT pathway, increasing tumour cell yield both in vitro and in vivo. Similar to the findings of Puvvada et al,22 and more recently Liu et al,31 we found BCL-3 expression was increased in colorectal cancer tissue, although it was often heterogeneous within the sample, with areas of strong staining adjacent to areas of moderate BCL-3 expression. We present evidence that this may be of particular importance in the context of surviving stresses such as hypoxia, encountered within the tumour microenvironment. As the pro-survival action of BCL-3 was also demonstrated in colorectal adenoma-derived cells, results suggest that targeting BCL-3 function may be effective both in the prevention and treatment of cancer.. The AKT/PKB pathway is an important signalling pathway involved in cell survival, inhibition of apoptosis, cell cycle progression and proliferation (reviewed in Zoncu et al50). ...
The invention provides a method of treating a disease or pathological condition resulting in apoptotic cell death. The method includes increasing the activity of Bcl-2 in cells affected by the disease or pathological condition. Diseases or pathological conditions can include, for example, neurodegenerative diseases, cancer and viral infections. Also provided is a method of prolonging the in vivo survival of transplanted cells for the treatment of a disease or pathological condition. 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. Diseases or pathological conditions can include, for example, neurodegenerative diseases, cancer and viral infections. 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. Methods to identify compounds that alter apoptotic cell death and to enhance monoclonal
Numerous studies using rats and mice have been conducted to examine the cellular mechanisms and processes involved in Alzheimers disease.. A study conducted by Um et al.[105] used transgenic mice Tg-NSE/hPS2m, which expressed the human PS2 mutation and compared them to control mice, who were labeled as non-Tg. Mice were sacrificed from each group and brains were removed and separated so the hippocampus and the extracted mitochondria could be analyzed using western blot analysis.[105] Tunel staining was also used to detect apoptosis.[105] It was found that phosphorylation levels of tau at the Ser404, Ser202, and Thr231 residues in the hippocampus in Tg mice were enhanced.[105] Increased phosphorylation levels of JNK1/2 and p38MAPK along with decreased levels of ERK1/2 phosphorylation were found in transgenic mice (Tg).[105] Tg mice also had higher levels of COX-2 proteins and higher levels of caspase-3 protein levels than control mice.[105] Cytochrome C and Bax protein levels were higher and ...
© Albert Einstein College of MedicineThis image depicts the structure of the BAX protein (purple). The activator compound BTSA1 (orange) has bound to the active site of BAX (green), changing the shape of the BAX molecule at several points (shown in yellow, magenta and cyan). BAX, once in its final activated form, can
In a phase II trial, some patients with heavily treated acute myelogenous leukemia (AML) benefited from treatment with the BCL-2 inhibitor venetoclax (ABT-199).
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Hypergastrinemia in INS-GAS mice leads to accelerated carcinogenesis of the stomach, but the mechanisms have not been well defined. We investigated the possible role of gastrin-induced gastric cell apoptosis in the development of gastric cancer. We examined apoptosis and the expression of Bcl-2 family proteins in INS-GAS mice of different ages, as well as in gastrin-deficient (GAS-KO) mice after gastrin-17 (G-17) infusion. In addition, we studied the effects of the gastrin/cholecystokinin-2 (CCK-2) receptor antagonist YF476 and/or histamine H2 (H-2) receptor antagonist loxtidine on apoptosis and atrophy in INS-GAS mice with or without Helicobacter felis (H. felis) infection. INS-GAS mice had age-associated increases in Bax protein expression and decreases in Bcl-2 protein expression, along with increased glandular and epithelial cell apoptosis. At 8-week gastrin infusions in GAS-KO mice resulted in a similar pattern of altered Bax and Bcl-2 expression, followed by gastric cell apoptosis. H. felis
Mice and primary neuronal cultures. Hq, Apaf1-/-, and Bax-/- mice were maintained and genotyped as described previously (Fortin et al., 2001; Klein et al., 2002). Cortical neurons and cerebellar granule neurons (CGNs) were cultured from cortices of E15.5 mice and cerebellums of postnatal day 7 mice, respectively, as described previously (Fortin et al., 2001). Recombinant adenoviral vectors carrying human AIF or LacZ expression cassettes were prepared and used at 50 multiplicity of infection as described previously (Cregan et al., 2002).. Camptothecin treatment and cell viability assays. Neurons were treated with 10 μm camptothecin with or without 10 μm Boc-aspartyl (Ome)-fluoromethylketone (BAF) (Enzyme System Products, Livermore, CA) after 2 d in vitro (DIV). Cell survival was measured by the following: live/dead staining (Molecular Probes, Eugene, OR), Hoechst staining, MTT assay (Cell Titer kit; Promega, Madison, WI), terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end ...
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Read "The Pro-Apoptotic Proteins, Bid and Bax, Cause a Limited Permeabilization of the Mitochondrial Outer Membrane That Is Enhanced by Cytosol, The Journal of Cell Biology" on DeepDyve, the largest online rental service for scholarly research with thousands of academic publications available at your fingertips.
In this report, we have established the mechanism of the apoptotic effect of a Bcl-2-interacting small molecule, HA14-1. HA14-1 binds Bcl-2 and neutralizes the antiapoptotic effect of Bcl-2. However, our cell-free mitochondrial study revealed that it is not enough to induce cytochrome c release by just blocking Bcl-2 with HA14-1. The translocation of Bax from the cytosol to the mitochondria is essential for the subsequent cytochrome c release. This study therefore provides an important clue regarding the primary effector in induction of cell death. Bcl-2 and Bax not only function through antagonizing each other but also have independent functions (22). Is the blocking of Bcl-2 or the activation of Bax more critical in triggering apoptosis? It has been very difficult to separate these two events due to the lack of critical tools. With the availability of HA14-1, we were able to achieve blockage of Bcl-2 in cell-free mitochondria to study the consequence of Bcl-2 blockage alone. Our result ...
When cells kill themselves, they usually do so by activating mechanisms that have evolved specifically for that purpose. These mechanisms, which are broadly conserved throughout the metazoa, involve two processes: activation in the cytosol of latent cysteine proteases (termed caspases), and disruption of mitochondrial functions. These processes are linked in a number of different ways. While active caspases can cleave proteins in the mitochondrial outer membrane, and cleave and thereby activate certain pro-apoptotic members of the Bcl-2 family, proteins released from the mitochondria can trigger caspase activation and antagonise IAP family proteins. This review will focus on the pro-apoptotic molecules that are released from the mitochondria of cells endeavouring to kill themselves. This article is part of a Special Issue entitled Mitochondria: the deadly organelle ...
DUBLIN, July 9, 2019 /PRNewswire/ -- The "Venclexta" report has been added to ResearchAndMarkets.coms offering. Drug Overview. Venclexta (venetoclax; AbbVie/Roche) is an inhibitor of the B-cell lymphoma-2 (BCL-2) family of proteins. This family of proteins is responsible for the regulation of cell death by either inducing or inhibiting apoptosis. Increased expression of BCL-2 can lead to resistance to apoptosis in cancer cells. Venclexta blocks the function of the BCL-2 protein, leading to an increase in pro-apoptotic proteins and restoration of normal apoptosis regulation ...
HONGFU, Liu et al. The Role and Significance of Bcl-2 and Bax in the Hepatic Carcinoma. Int. J. Morphol. [online]. 2012, vol.30, n.4, pp.1466-1473. ISSN 0717-9502. http://dx.doi.org/10.4067/S0717-95022012000400032.. This study aimed to observe the regularity of liver cell apoptosis and expression of apoptosis related gene Bcl-2 and Bax in the induced cancer, and explore the relationship between apoptosis and the development of liver cancer. In this study, 84 rats were used, 72 rats as experimental group induced by drinking water containing DEN, 12 rats as control group (CG). After laparotomy, the form, color, texture of the liver and metastatic tumor in both control and experimental groups were observed and recorded. The metastatic tumor and the liver tissue were sectioned and stained with hematoxylin-eosin staining to demonstrate the characteristic in morphological changes, the Hoechst 33342 fluorescent staining was applied to show and count the rate of apoptotic cell, and the in situ ...
Sigma-Aldrich offers abstracts and full-text articles by [Shanshan Song, Krista N Jacobson, Kimberly M McDermott, Sekhar P Reddy, Anne E Cress, Haiyang Tang, Steven M Dudek, Stephen M Black, Joe G N Garcia, Ayako Makino, Jason X-J Yuan].
【Promotion】Abbkine Selected Primary Antibody-Click for Promotion details. Bcl-2 gene (B-cell lymphoma-2) is a member of Bcl-2 family, which is the earliest discovered apoptosis protein. It is an anti-apoptosis protei,,
Abstract: 目的 研究蟾蜍灵联合奥沙利铂诱导人胃癌细胞株MG C803凋亡及对凋亡因子Bax、Bcl-2的影响.方法 应用MTr法检测不同浓度蟾蜍灵及奥沙利铂单药及联合对胃癌细胞MGC803增殖抑制作用;流式细胞术分析细胞凋亡和周期阻滞;Western印迹法检测Bax、Bcl-2蛋白的表达.结果 (1)蟾蜍灵及奥沙利铂单药均抑制MGC803细胞增殖,呈剂量时间依赖效应,且联合用药的细胞增殖抑制率高于单药组,差... ...
In this work, we studied the expression of Bcl-2 family proteins (Bcl-2, Bcl-X, Bax, and Bak) in tissues from long-lived patients with chemosensitive NHL and short-lived patients with chemoresistant NHL. The high curability of NHL large-cell type with chemotherapy allowed us the rare opportunity to study the reasons for the success or failure of the present chemotherapeutic approach in patients with similar pathology. Bcl-2 and Bcl-X proteins are implicated in multidrug chemoresistance in tumors. Individual cell types vary considerably in their levels of the Bcl-2 family members. Bcl-2, the most thoroughly investigated, is a potent suppressor of apoptosis and is found at inappropriately high levels in probably ,50% of all cancers in humans (15) . Moreover, the relationship between Bcl-2 and chemoresistance has been borne out by clinical correlative studies showing that elevated expression of this protein may be associated with short survival and other indicators of poor clinical outcome in ...
Apoptosis regulator BAX TranslationBlocker™ siRNA. Tested in Human samples. The only siRNA validated in protein knockdown with detailed protocols. From: $219.
Expression analysis of BCL2L12, a new member of apoptosis-related genes, in colon cancer.: Apoptosis is an active process regulated by a variety of genes. Recen
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... have signed a strategic global collaboration agreement with Novartis to develop and commercialize a series of novel drugs candidates issued from the Servier research programs partnered with Vernalis in oncology which are targeting the apoptosis regulation pathways. Read the full story ...
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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 ...
Preeclampsia is associated with placental hypoxia at early gestation. We therefore investigated the effect of hypoxia on the apoptosis of cultured first trimester human cytotrophoblasts and the expression of apoptosis relevant proteins, Bcl-2 and Bax. First trimester human cytotrophoblasts were isolated and cultured under either standard or hypoxic conditions. Cellular apoptosis was monitored by TUNEL and Annexin V binding, and the expression of Bcl-2 and Bax was determined by Western blot analysis. Apoptosis increased significantly in cytotrophoblasts cultured for 24 h under hypoxic conditions in contrast with those cultured under standard conditions, meanwhile expression of Bcl-2 reduced, and that of Bax increased. These changes suggested that hypoxia induced apoptosis in cultured first trimester cytotrophoblasts with altered Bcl-2 and Bax expression. Further study is needed to explore the role of cytotrophoblasts apoptosis in hypoxia-induced maternal and fetal diseases. © 2006 Elsevier Inc. ...
PubMed Central Canada (PMC Canada) provides free access to a stable and permanent online digital archive of full-text, peer-reviewed health and life sciences research publications. It builds on PubMed Central (PMC), the U.S. National Institutes of Health (NIH) free digital archive of biomedical and life sciences journal literature and is a member of the broader PMC International (PMCI) network of e-repositories.
Endometrial cancer is a common malignancy of the female genital tract. This study demonstrates that Siegesbeckia orientalis ethanol extract (SOE) significantly inhibited the proliferation of RL95-2 human endometrial cancer cells. Treating RL95-2 cells with SOE caused cell arrest in the G2/M phase and induced apoptosis of RL95-2 cells by up-regulating Bad, Bak and Bax protein expression and down-regulation of Bcl-2 and Bcl-xL protein expression. Treatment with SOE increased protein expression of caspase-3, -8 and -9 dose-dependently, indicating that apoptosis was through the intrinsic and extrinsic apoptotic pathways. Moreover, SOE was also effective against A549 (lung cancer), Hep G2 (hepatoma), FaDu (pharynx squamous cancer), MDA-MB-231 (breast cancer), and especially on LNCaP (prostate cancer) cell lines. In total, 10 constituents of SOE were identified by Gas chromatography-mass analysis. Caryophyllene oxide and caryophyllene are largely responsible for most cytotoxic activity of SOE against RL95-2
Germinal centers (GCs) are the main site of T cell-dependent antibody responses. Upon antigen challenge, GCs comprise mostly B cells undergoing proliferation, somatic hypermutation and antigen-affinity selection. GC B cells down-modulate the expression of Bcl-2 protein and are highly sensitive to apoptosis to eliminate autoreactive or low-affinity cells. Bcl-2 is still expressed in a few GC cells, whose identity remains unclear. To address this issue, we examined by confocal microscopy the expression of Bcl-2 by different GC lymphocyte subsets in hyperplastic tonsils. We found that the vast majority of Bcl-2+ GC cells are T lymphocytes. Conversely, while in the mantle zone and in the interfollicular areas T cells are almost exclusively Bcl-2 +, in the GC, most T lymphocytes are Bcl-2-. In addition, most of the CD4+ GC T cells are Bcl-2-, while nearly 100% of the CD8+ GC T cells are Bcl-2+. The Bcl-2 downregulation by both B and CD4+ T GC cells supports the concept that these two subsets may ...
Objective - Pro-inflammatory cytokines are cytotoxic to β-cells and have been implicated in the pathogenesis of type 1 diabetes and islet graft failure. The importance of the intrinsic mitochondrial apoptotic pathway in cytokine-induced β-cell death is unclear. Here, cytokine activation of the intrinsic apoptotic pathway and the role of the two pro-apoptotic Bcl-2 proteins, Bad and Bax were examined in β-cells.. Research Design and Methods - Human islets, rat islets, and INS-1 cells were exposed to a combination of pro-inflammatory cytokines: interleukin (IL)-1β, interferon (IFN)γ and/or tumor necrosis factor (TNF)α. Activation of Bad was determined by Ser136 dephosphorylation; mitochondrial stress by changes in mitochondrial metabolic activity and cytochrome c release; and downstream apoptotic signalling by activation of caspase-9 and -3, and DNA fragmentation. The inhibitors FK506 and V5 were used to investigate the role of Bad and Bax activation, respectively.. Results - We found that ...
Waldenström macroglobulinemia (WM) is a proliferative disorder of IgM-secreting, lymphoplasmacytoid cells that inhabit the lymph nodes and bone marrow. The disease carries a high prevalence of activating mutations in MyD88 (91%) and CXCR4 (28%). Because signaling through these pathways leads to Bcl-xL induction, we examined Bcl-2 family expression in WM patients and cell lines. Unlike other B-lymphocyte-derived malignancies, which become dependent on expression of anti-apoptotic proteins to counter expression of pro-apoptotic proteins, WM samples expressed both pro- and anti-apoptotic Bcl-2 proteins at low levels similar to their normal B-cell and plasma cell counterparts. Three WM cell lines expressed pro-apoptotic Bcl-2 family members Bim or Bax and Bak at low levels, which determined their sensitivity to inducers of intrinsic apoptosis. In two cell lines, miR-155 upregulation, which is common in WM, was responsible for the inhibition of FOXO3a and Bim expression. Both antagonizing miR-155 to ...
Our previous study found that the knockdown of MUC1 in SMMC-7721 cells can significantly inhibit cell proliferation and induce cell cycle arrest (23). In the present study, a clone formation assay in vitro and a tumor xenograft mouse model with an in vivo imaging system were utilized and the growth inhibitory effects of MUC1 silencing in SMMC-7721 cells were further confirmed. Since MUC1 is an oncoprotein, it is not only involved in the regulation of carcinogenesis and tumor progression, invasion and metastasis (2), but it is also important in the inhibition of cell apoptosis (25-27). Consequently, the present study examined in depth whether the growth inhibition of MUC1 gene-silenced cells is associated with apoptotic cell death. Hoechst 33342 staining, flow cytometry with Annexin V-PE staining and a DNA Ladder assay were performed, and all results consistently demonstrated that MUC1 gene silencing induces cells to undergo apoptosis. These results are similar to results from a previous study, ...
Sigma-Aldrich offers abstracts and full-text articles by [Chien-Chang Huang, Cheng-Che Lee, Hsiao-Han Lin, Mei-Chi Chen, Chun-Cheng Lin, Jang-Yang Chang].
Interleukin-5 inhibits translocation of Bax to the mitochondria, cytochrome c release, and activation of caspases in human eosinophils ...
The BH3-only apoptosis agonists BAD and NOXA target BCL-2 and MCL-1 respectively and co-operate to induce apoptosis. On this basis, therapeutic drugs targeting BCL-2 and MCL-1 might have enhanced activity if used in combination. We identified anti-leukaemic drugs sensitising to BCL-2 antagonism and drugs sensitising to MCL-1 antagonism using the technique of dynamic BH3 profiling, whereby cells were primed with drugs to discover whether this would elicit mitochondrial outer membrane permeabilisation in response to BCL-2-targeting BAD-BH3 peptide or MCL-1-targeting MS1-BH3 peptide. We found that a broad range of anti-leukaemic agents-notably MCL-1 inhibitors, DNA damaging agents and FLT3 inhibitors-sensitise leukaemia cells to BAD-BH3. We further analysed the BCL-2 inhibitors ABT-199 and JQ1, the MCL-1 inhibitors pladienolide B and torin1, the FLT3 inhibitor AC220 and the DNA double-strand break inducer etoposide to correlate priming responses with co-operative induction of apoptosis. ABT-199 in ...
Although the vast majority of patients with a myelodysplastic syndrome (MDS) suffer from cytopenias, the bone marrow is usually normocellular or hypercellular. Apoptosis of hematopoietic cells in the bone marrow has been implicated in this phenomenon. However, in MDS it remains only partially elucidated which genes are involved in this process and which hematopoietic cells are mainly affected. We employed sensitive real-time PCR technology to study 93 apoptosis-related genes and gene families in sorted immature CD34+ and the differentiating erythroid (CD71+) and monomyeloid (CD13/33+) bone marrow cells. Unsupervised cluster analysis of the expression signature readily distinguished the different cellular bone marrow fractions (CD34+, CD71+ and CD13/33+) from each other, but did not discriminate patients from healthy controls. When individual genes were regarded, several were found to be differentially expressed between patients and controls. Particularly, strong over-expression of BIK (BCL2-interacting
TY - JOUR. T1 - Bcl-2 and bax expression and prostate cancer outcome in men treated with radiotherapy in Radiation Therapy Oncology Group protocol 86-10. AU - Khor, Li Yan. AU - DeSilvio, Michelle. AU - Li, Rile. AU - McDonnell, Timothy J.. AU - Hammond, M. Elizabeth H. AU - Sause, William T.. AU - Pilepich, Miljenko V.. AU - Okunieff, Paul. AU - Sandler, Howard M.. AU - Pollack, Alan. PY - 2006/9/1. Y1 - 2006/9/1. N2 - Purpose: Bcl-2 and bax are proteins with opposing roles in apoptosis regulation; yet abnormal expression of either has been associated with failure after radiotherapy (RT). In this study we examined bcl-2 and bax expression as predictive markers in men treated with radiotherapy ± androgen deprivation on Radiation Therapy Oncology Group (RTOG) protocol 86-10. Experimental Design: Suitable archival diagnostic tissue was obtained from 119 (26%) patients for bcl-2 analysis and 104 (23%) patients for bax analysis. Cox proportional hazards multivariate analysis was used to determine ...
The initiating events that lead to the induction of apoptosis mediated by the chemopreventative agent β-phenyethyl isothiocyanate (PEITC) have yet to be elucidated. In the present investigation, we examined the effects of PEITC on mitochondrial function and apoptotic signaling in hepatoma HepG2 cells and isolated rat hepatocyte mitochondria. PEITC induced a conformational change in Bax leading to its translocation to mitochondria in HepG2 cells. Bax accumulation was associated with a rapid loss of mitochondrial membrane potential (Δψm), impaired respiratory chain enzymatic activity, release of mitochondrial cytochrome c and the activation of caspase-dependent cell death. Caspase inhibition did not prevent Bax translocation, the release of cytochrome c or the loss of Δψ m, but blocked caspase-mediated DNA fragmentation and cell death. To determine whether PEITC dependent Bax translocation caused loss of Δψm by the activation of the mitochondrial permeability transition (MPT), we examined ...
TY - JOUR. T1 - Intramitochondrial recruitment of endolysosomes mediates Smac degradation and constitutes a novel intrinsic apoptosis antagonizing function of XIAP E3 ligase. AU - Hamacher-Brady, Anne. AU - Choe, S. C.. AU - Krijnse-Locker, J.. AU - Brady, Nathan Ryan. PY - 2014/12/1. Y1 - 2014/12/1. N2 - Intrinsic apoptosis involves BH3-only protein activation of Bax/Bak-mediated mitochondrial outer membrane permeabilization (MOMP). Consequently, cytochrome c is released from the mitochondria to activate caspases, and Smac (second mitochondria-derived activator of caspases) to inhibit XIAP-mediated caspase suppression. Dysfunctional mitochondria can be targeted for lysosomal degradation via autophagy (mitophagy), or directly through mitochondria-derived vesicle transport. However, the extent of autophagy and lysosomal interactions with apoptotic mitochondria remains largely unknown. We describe here a novel pathway of endolysosomal processing of mitochondria, activated in response to canonical ...
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 ...
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 ...
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- ...
... 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 ...
... 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 and 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 ...
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 ...
"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. ...
"Directed elimination of senescent cells by inhibition of BCL-W and BCL-XL". Nature Communications. 7: 11190. doi:10.1038/ ... "An inhibitor of Bcl-2 family proteins induces regression of solid tumours". Nature. 435 (7042): 677-81. doi:10.1038/nature03579 ...
Li L, Li HS, Pauza CD, Bukrinsky M, Zhao RY (2006). "Roles of HIV-1 auxiliary proteins in viral pathogenesis and host-pathogen ... SLC25A4 has been shown to interact with Bcl-2-associated X protein. GRCh38: Ensembl release 89: ENSG00000151729 - Ensembl, May ... Le Rouzic E, Benichou S (2006). "The Vpr protein from HIV-1: distinct roles along the viral life cycle". Retrovirology. 2: 11. ... Zhao RY, Bukrinsky M, Elder RT (Apr 2005). "HIV-1 viral protein R (Vpr) & host cellular responses". The Indian Journal of ...
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. Mol". Brain Res. 95 ... "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): ... Bae J, Leo CP, Hsu SY, Hsueh AJ (August 2000). "MCL-1S, a splicing variant of the antiapoptotic BCL-2 family member MCL-1, ...
Many viruses encode proteins that can inhibit apoptosis.[94] Several viruses encode viral homologs of Bcl-2. These homologs can ... 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.[74] These tumor-suppressing proteins regulate the ... Finally, the Akt protein kinase promotes cell survival through two pathways. Akt phosphorylates and inhibits Bas (a Bcl-2 ...
... 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 ...
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 Bas (a Bcl-2 ...
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 ...
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 ...
... 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 ...
... 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. The SOD1 enzyme is an ...
Overexpression of this protein induces apoptosis, which can be suppressed by co-expression of BCL2 proteins. The protein ... Bcl-2-associated transcription factor 1 is a Bcl-2 family protein in humans that is encoded by the BCLAF1 gene. This gene ... Liu H, Lu ZG, Miki Y, Yoshida K (2007). "Protein Kinase C δ Induces Transcription of the TP53 Tumor Suppressor Gene by ... Mansharamani M, Wilson KL (2005). "Direct binding of nuclear membrane protein MAN1 to emerin in vitro and two modes of binding ...
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 ...
This protein interacts with either BCL-2 or PI3k class III, playing a critical role in the regulation of both autophagy and ... "A protein-protein interaction network for human inherited ataxias and disorders of Purkinje cell degeneration". Cell. 125 (4): ... Beclin-1 is a protein that in humans is encoded by the BECN1 gene. Beclin-1 is a mammalian ortholog of the yeast autophagy- ... Yue Z, Horton A, Bravin M, DeJager PL, Selimi F, Heintz N (Aug 2002). "A novel protein complex linking the delta 2 glutamate ...
Strong expression of the Bcl-2 protein in the DLBCL infiltrate, objective magnification 40×. ... an E3 ubiquitin ligase complex co-receptor protein [29]. ... Figure 2. Treatment schema. ASCT-Z-BEAM, autologous stem cell ... 2.. Tilly H, Vitolo U, Walewski J, da Silva MG, Shpilberg O, Andre M, Pfreundschuh M, Dreyling M: Diffuse large B-cell lymphoma ... Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research , View latest news , Sign up for updates ...
A subset of adult-mBL had BCL2 translocation and mutation and elevated BCL2 mRNA and protein expression, but had a mutation ... A subset of adult-mBL had BCL2 translocation and mutation and elevated BCL2 mRNA and protein expression, but had a mutation ... A subset of adult-mBL had BCL2 translocation and mutation and elevated BCL2 mRNA and protein expression, but had a mutation ... A subset of adult-mBL had BCL2 translocation and mutation and elevated BCL2 mRNA and protein expression, but had a mutation ...
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 ...
"Identification of the protein-protein contact site and interaction mode of human VDAC1 with Bcl-2 family proteins". Biochem. ... 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 ... is a protein that in humans is encoded by the BAX gene. BAX is a member of the Bcl-2 gene family. BCL2 family members form ...
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 ...
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 ...
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 ...
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- ...
Bok, for example, interacts with Mcl-1 and the Epstein-Barr viral protein BHRF1 but not with Bcl-2, Bcl-xL, or Bcl-w (24). ... The pro-survival proteins also seem to maintain organelle integrity. Bcl-2 directly or indirectly prevents the release from ... 4). CED-9 and Bcl-xL can bind to CED-4, which also binds CED-3 and stimulates its activation (28, 29). The BH4 region of Bcl-xL ... These "BH3 domain" proteins (19) may well represent the physiological antagonists of the pro-survival proteins, because ...
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, ...
  • The growing Bcl-2 family can somehow register diverse forms of intracellular damage, gauge whether other cells have provided a positive or negative stimulus, and integrate these competing signals to determine whether the cell is "to be or not to be. (sciencemag.org)
  • 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)
  • Novus provides highly purified control peptides and proteins to ensure reliable results and reproducibility. (novusbio.com)
  • Pools of overlapping peptides from antigenic proteins for T-cell stimulation, T-cell expansion in T-cell assays such as ELISPOT, ICS or Flow Cytometry, e.g. for immune monitoring. (jpt.com)
  • Sequence alignment of the ASPP2-binding peptides combined with binding studies of mutated peptides revealed that two nonconserved positions where only Bcl-2 contains positively charged residues account for its tighter binding. (jpt.com)
  • Custom ELISA Kits, Recombinant Proteins and Antibodies can be designed, manufactured and produced according to the researcher's specifications. (mybiosource.com)
  • 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)
  • 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)
  • 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 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)
  • Using peptide arrays and quantitative binding studies, we found that Bcl-2 binds three loops in ASPP2(Ank-SH3) with similar affinity, in agreement with our predicted model. (jpt.com)
  • 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)
  • Is the Subject Area "Protein interactions" applicable to this article? (plos.org)
  • The C-terminal ankyrin repeats and SH3 domain of ASPP2 (ASPP2(Ank-SH3)) mediate its interactions with the antiapoptotic protein Bcl-2. (jpt.com)
  • p53 and p21 may form complexes with many other proteins. (aacrjournals.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)
  • 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)
  • The experimental binding results served as a basis for docking analysis, by which we modeled the complexes of ASPP2(Ank-SH3) with the full-length Bcl proteins. (jpt.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)
  • Bcl-2 Proteins in Mechanism of Anti-mitotic Drug Action Narrative: Anti-tumor drugs are widely used in cancer treatment. (grantome.com)
  • In the present study, we have attempted to establish whether the expression of apoptosis-related proteins in the presenting tumor in NHL can serve as a predictor of apoptosis and response or resistance to chemotherapy. (aacrjournals.org)
  • Bcl-2 and p53 expression might play an important role in the early development and phenotypic differentiation of gastric carcinomas, but not so in tumor progression. (ac.ir)
  • The aim of this study was to investigate expression of cyclin D1, bcl-2, p53, Ki-67 and HER-2 proteins in 14 cases of non-small cell lung cancer and to establish their correlation to classical clinico-pathological findings, and alleged prognostic value to estimate biological potential of tumor. (bjbms.org)
  • Negative expression of bcl-2 protein points out to possibility that it is not included into process of tumor apoptosis, as well as that proteins cyclin D1 and HER-2 are not included into processes of the tumor genesis. (bjbms.org)
  • Since the prolif-erative activity of the tumor, measured by the expression of Ki-67, is correlated to the gradus and size of the tumor mass, Ki-67 protein can be of a prognostic value to determine biological potential of non-small cell lung cancer. (bjbms.org)
  • We examined in vitro effects of G3139 on Bcl-2 mRNA and protein expression and combined effects of G3139 and cytotoxic drugs on viability/proliferation in the cell line RS4:11, which originally was derived from a case of adult ALL with t(4;11). (aacrjournals.org)
  • At 50 μM, G3139 treatment resulted in 15% reduction in Bcl-2 mRNA compared to treatment with G3622. (aacrjournals.org)
  • The t(14;18) translocation results in a hybrid bcl-2/immunoglobulin heavy chain transcript consisting of the 5' half of the bcl-2 mRNA fused to a truncated immunoglobulin heavy chain mRNA. (thefreedictionary.com)
  • 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)
  • AML myeloblasts also show higher BCL-2 mRNA phrase than regular bone marrow (Figure 4F). (biogeology.org)
  • 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)
  • In addition, ER stress is also known to induce autophagy to counteract XBP-1-mediated ER expansion and assist in the degradation of unfolded proteins. (physiology.org)
  • Paraquat does induce lung tissue inflammation, which in turn increases Bcl-2 protein expression. (ac.ir)
  • The modulation of various regulatory proteins involved in metabolic processes is central to cancerous reprogramming of metabolism. (biomedcentral.com)
  • 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)
  • Function of apoptosis and expression of the proteins Bcl-2, p53 and C-myc in the development of gastric cancer. (ac.ir)
  • 6. Zheng Y, Wang L, Zhang J-P, Yang J-Y, Zhao Z-M, Zhang X-Y. Expression of p53, c-erbB-2 and Ki67 in intestinal metaplasia and gastric carcinoma. (ac.ir)
  • Prognostic significance of Bcl-2 and p53 expression in gastric cancer. (ac.ir)
  • 14. Liu H-F, Liu W-W, Fang D-C, Men R-P. Expression of bcl-2 protein in gastric carcinoma and its significance. (ac.ir)
  • In the presented studies p53 and bcl-2 proteins expression were evaluated in samples of gastric carcinomas in patients with Helicobacter pylori or EBV or without H. pylori /EBV infection. (pjmonline.org)
  • The studies were conducted on 64 adult patients with gastric adenocarcinomas: 16 patients with H. pylori ( cagA +)-positivity (group 1), 14 with EBV-positive tumours (group 2), 12 with H. pylori /EBV-positive tumours (group 3) and 22 patients with H. pylori /EBV-negative tumours (group 4). (pjmonline.org)
  • Nevertheless, it remains unclear whether in gastric carcinoma p53 abnormali-ties and bcl-2 expression are dependent on presence of H. pylori or EBV infection. (pjmonline.org)
  • Among the proteins involved in this response are nutrient-deprivation autophagy factor-1 (NAF-1)- and Bcl-2. (sigmaaldrich.com)
  • NAF-1 is an important partner for Bcl-2 at the endoplasmic reticulum to functionally antagonize Beclin 1-dependent autophagy [Chang NC, Nguyen M, Germain M, Shore GC (2010) EMBO J 29(3):606- (sigmaaldrich.com)
  • 2 There exists considerable debate, however, as to whether autophagy functions as a death process. (ahajournals.org)