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.

Bcl-2 regulates amplification of caspase activation by cytochrome c. (1/2563)

Caspases, a family of specific proteases, have central roles in apoptosis [1]. Caspase activation in response to diverse apoptotic stimuli involves the relocalisation of cytochrome c from mitochondria to the cytoplasm where it stimulates the proteolytic processing of caspase precursors. Cytochrome c release is controlled by members of the Bcl-2 family of apoptosis regulators [2] [3]. The anti-apoptotic members Bcl-2 and Bcl-xL may also control caspase activation independently of cytochrome c relocalisation or may inhibit a positive feedback mechanism [4] [5] [6] [7]. Here, we investigate the role of Bcl-2 family proteins in the regulation of caspase activation using a model cell-free system. We found that Bcl-2 and Bcl-xL set a threshold in the amount of cytochrome c required to activate caspases, even in soluble extracts lacking mitochondria. Addition of dATP (which stimulates the procaspase-processing factor Apaf-1 [8] [9]) overcame inhibition of caspase activation by Bcl-2, but did not prevent the control of cytochrome c release from mitochondria by Bcl-2. Cytochrome c release was accelerated by active caspase-3 and this positive feedback was negatively regulated by Bcl-2. These results provide evidence for a mechanism to amplify caspase activation that is suppressed at several distinct steps by Bcl-2, even after cytochrome c is released from mitochondria.  (+info)

Bcl-2 and Bcl-XL serve an anti-inflammatory function in endothelial cells through inhibition of NF-kappaB. (2/2563)

To maintain the integrity of the vascular barrier, endothelial cells (EC) are resistant to cell death. The molecular basis of this resistance may be explained by the function of antiapoptotic genes such as bcl family members. Overexpression of Bcl-2 or Bcl-XL protects EC from tumor necrosis factor (TNF)-mediated apoptosis. In addition, Bcl-2 or Bcl-XL inhibits activation of NF-kappaB and thus upregulation of proinflammatory genes. Bcl-2-mediated inhibition of NF-kappaB in EC occurs upstream of IkappaBalpha degradation without affecting p65-mediated transactivation. Overexpression of bcl genes in EC does not affect other transcription factors. Using deletion mutants of Bcl-2, the NF-kappaB inhibitory function of Bcl-2 was mapped to bcl homology domains BH2 and BH4, whereas all BH domains were required for the antiapoptotic function. These data suggest that Bcl-2 and Bcl-XL belong to a cytoprotective response that counteracts proapoptotic and proinflammatory insults and restores the physiological anti-inflammatory phenotype to the EC. By inhibiting NF-kappaB without sensitizing the cells (as with IkappaBalpha) to TNF-mediated apoptosis, Bcl-2 and Bcl-XL are prime candidates for genetic engineering of EC in pathological conditions where EC loss and unfettered activation are undesirable.  (+info)

Constitutive activation of Stat3 signaling confers resistance to apoptosis in human U266 myeloma cells. (3/2563)

Interleukin 6 (IL-6) is the major survival factor for myeloma tumor cells and induces signaling through the STAT proteins. We report that one STAT family member, Stat3, is constitutively activated in bone marrow mononuclear cells from patients with multiple myeloma and in the IL-6-dependent human myeloma cell line U266. Moreover, U266 cells are inherently resistant to Fas-mediated apoptosis and express high levels of the antiapoptotic protein Bcl-xL. Blocking IL-6 receptor signaling from Janus kinases to the Stat3 protein inhibits Bcl-xL expression and induces apoptosis, demonstrating that Stat3 signaling is essential for the survival of myeloma tumor cells. These findings provide evidence that constitutively activated Stat3 signaling contributes to the pathogenesis of multiple myeloma by preventing apoptosis.  (+info)

In vitro induction of activation-induced cell death in lymphocytes from chronic periodontal lesions by exogenous Fas ligand. (4/2563)

Periodontitis is a chronic inflammatory disease which gradually destroys the supporting tissues of the teeth, leading to tooth loss in adults. The lesions are characterized by a persistence of inflammatory cells in gingival and periodontal connective tissues. To understand what mechanisms are involved in the establishment of chronic lesions, we hypothesized that infiltrating lymphocytes might be resistant to apoptosis. However, both Bcl-2 and Bcl-xL were weakly detected in lymphocytes from the lesions, compared with those from peripheral blood, suggesting that these cells are susceptible to apoptosis. Nevertheless, very few apoptotic cells were observed in tissue sections from the lesions. Lymphocytes from the lesions expressed mRNA encoding Fas, whereas Fas-ligand mRNA was very weakly expressed in lymphocytes from the lesions and in periodontal tissues. Since the results indicated that lymphocytes in the lesions might be susceptible to Fas-mediated apoptosis but lack the death signal, we next investigated if these lymphocytes actually undergo apoptosis by the addition of anti-Fas antibodies in vitro. Fas-positive lymphocytes from the lesions underwent apoptosis by these antibodies, but Fas-negative lymphocytes and Fas-positive peripheral lymphocytes did not undergo apoptosis by these antibodies. These results indicate that lymphocytes in the lesions are susceptible to activation-induced cell death and are induced to die by apoptosis after the addition of exogenous Fas ligand.  (+info)

Control of apoptosis in Epstein Barr virus-positive nasopharyngeal carcinoma cells: opposite effects of CD95 and CD40 stimulation. (5/2563)

The expression and function of CD95 and CD40 were investigated in malignant cells from EBV-positive undifferentiated nasopharyngeal carcinomas (NPCs). Large amounts of CD95 and CD40 expression were detected in 15 of 16 EBV-positive NPC specimens. In contrast, CD95 was not detected in two biopsies from patients with EBV-negative differentiated NPCs. We tested whether the CD95 apoptotic pathway was functional in NPC cells by treating two EBV-positive NPC tumor lines in vitro with a CD95 agonist. In both cases, NPC cells were extremely susceptible to CD95-mediated apoptosis, despite strong constitutive expression of Bcl-x. Combined CD40 and CD95 stimulation was used to investigate the possible anti-apoptotic activity mediated by CD40. The CD40 receptor was activated by incubating NPC cells with murine L cells producing CD154, the CD40 ligand. This treatment resulted in a strong inhibition of CD95-related cytotoxicity. Such an anti-apoptotic effect of CD40 is well known for B lymphocytes, but has not previously been reported for epithelial cells. These data suggest that NPC tumor-infiltrating lymphocytes, which often produce the CD40 ligand in situ, may increase the survival of malignant cells, thereby enhancing tumor growth in patients.  (+info)

Role of cytokine signaling molecules in erythroid differentiation of mouse fetal liver hematopoietic cells: functional analysis of signaling molecules by retrovirus-mediated expression. (6/2563)

Erythropoietin (EPO) and its cell surface receptor (EPOR) play a central role in proliferation, differentiation, and survival of erythroid progenitors. Signals induced by EPO have been studied extensively by using erythroid as well as nonerythroid cell lines, and various controversial results have been reported as to the role of signaling molecules in erythroid differentiation. Here we describe a novel approach to analyze the EPO signaling by using primary mouse fetal liver hematopoietic cells to avoid possible artifacts due to established cell lines. Our strategy is based on high-titer retrovirus vectors with a bicistronic expression system consisting of an internal ribosome entry site (IRES) and green fluorescent protein (GFP). By placing the cDNA for a signaling molecule in front of IRES-GFP, virus-infected cells can be viably sorted by fluorescence-activated cell sorter, and the effect of expression of the signaling molecule can be assessed. By using this system, expression of cell-survival genes such as Bcl-2 and Bcl-XL was found to enhance erythroid colony formation from colony-forming unit-erythroid (CFU-E) in response to EPO. However, their expression was not sufficient for erythroid colony formation from CFU-E alone, indicating that EPO induces signals for erythroid differentiation. To examine the role of EPOR tyrosine residues in erythroid differentiation, we introduced a chimeric EGFR-EPOR receptor, which has the extracellular domain of the EGF receptor and the intracellular domain of the EPOR, as well as a mutant EGFR-EPOR in which all the cytoplasmic tyrosine residues are replaced with phenylalanine, and found that tyrosine residues of EPOR are essential for erythroid colony formation from CFU-E. We further analyzed the function of the downstream signaling molecules by expressing modified signaling molecules and found that both JAK2/STAT5 and Ras, two major signaling pathways activated by EPOR, are involved in full erythroid differentiation.  (+info)

Rubella virus-induced apoptosis varies among cell lines and is modulated by Bcl-XL and caspase inhibitors. (7/2563)

Rubella virus (RV) causes multisystem birth defects in the fetuses of infected women. To investigate the cellular basis of this pathology, we examined the cytopathic effect of RV in three permissive cell lines: Vero 76, RK13, and BHK21. Electron microscopy and the TUNEL assay showed that the cytopathic effect resulted from RV-induced programmed cell death (apoptosis) in all three cell lines, but the extent of apoptosis varied among these cells. At 48 h postinfection, the RK13 cell line showed the greatest number of apoptotic cells, the Vero 76 cell line was approximately 3-fold less, and BHK21 had very few. An increased multiplicity of infection and longer time postinfection were required for the BHK21 cell line to reach the level of apoptotic cells in Vero 76 at 48 h. Purified RV induced apoptosis in a dose-dependent fashion, but not UV-inactivated RV or virus-depleted culture supernatant. Specific inhibitors of the apoptosis-specific proteases caspases reduced RV-induced apoptosis and led to higher levels of RV components in infected cells. To address the role of regulatory proteins in RV-induced apoptosis, the antiapoptotic gene Bcl-2 or Bcl-XL was transfected into RK13 cells. Although a high level of Bcl-2 family proteins was expressed, no protection was observed from apoptosis induced by RV, Sindbis virus, or staurosporine in RK13 cells. In BHK21 cells, however, increased expression of Bcl-XL protected cells from apoptosis. The observed variability in apoptotic response to RV of these cell lines demonstrates that programmed cell death is dependent on the unique properties of each cell and may be indicative of how selective organ damage occurs in a congenital rubella syndrome fetus.  (+info)

Bcl-2 overexpression results in reciprocal downregulation of Bcl-X(L) and sensitizes human testicular germ cell tumours to chemotherapy-induced apoptosis. (8/2563)

Testicular germ cell tumours are hypersentive to chemotherapy and cell lines derived from these tumours are chemosensitive in vitro. We have previously shown that these cell lines express undetectable levels of the suppressor of apoptosis Bcl-2 and relatively high levels of the apoptosis inducer Bax (Chresta et al., 1996). To determine whether the absence of Bcl-2 in these cell lines makes them highly susceptible to drug-induced apoptosis, Bcl-2 was expressed ectopically in the 833K testicular germ cell tumour cell line. Stable overexpressing clones were isolated and three clones were studied further. Surprisingly, Bcl-2 overexpressing cells were sensitized to chemotherapy-induced apoptosis compared to the parental and vector control cells. Analysis of potential mechanisms of sensitization revealed there was a reciprocal downregulation of the endogenously expressed Bcl-X(L) in the Bcl-2 overexpressing clones. Downregulation of Bcl-X(L) to the same extent using antisense oligonucleotides enhanced etoposide-induced apoptosis by twofold. Our results indicate that Bcl-2 and Bcl-X(L) have different abilities to protect against chemotherapy-induced apoptosis in testicular germ cell tumours. In contrast to findings in some tumour cell types, Bcl-2 did not act as a gatekeeper to prevent entry of p53 to the nucleus.  (+info)

*Bcl-2-associated X protein

... also known as bcl-2-like protein 4, is a protein that in humans is encoded by the BAX gene. BAX is a member of the Bcl-2 gene ... Bcl-2-associated X protein has been shown to interact with: Bcl-2, BCL2L1, BCL2A1 SH3GLB1, SLC25A4, VDAC1, TCTP, YWHAQ, Bid, ... The BAX gene was the first identified pro-apoptotic member of the Bcl-2 protein family. Bcl-2 family members share one or more ... "Identification of the protein-protein contact site and interaction mode of human VDAC1 with Bcl-2 family proteins". Biochem. ...

*Rudolf K. Allemann

"Photocontrollable Peptide-Based Switches Target the Anti-Apoptotic Protein Bcl-X-L". ChemBioChem. 9 (18): 3046-3054. doi: ... CS1 maint: Multiple names: authors list (link) Luk, YPL Loveridge, EJ Allemann, RK (2015). "Protein motions and dynamic effects ... dihydrofolate reductase has led to deep new insights into the contributions from quantum mechanical tunnelling and protein ...

*Jerry Adams

"The Bcl-2 protein family: arbiters of cell survival". Science. 281 (5381): 1322-6. doi:10.1126/science.281.5381.1322. PMID ... while studying the bcl-2 gene in follicular lymphoma, the most common human lymphoma. He studied for his B.Sc at Emory ...

*Hypothermia therapy for neonatal encephalopathy

2001). "Mild hypothermia increases Bcl-2 protein expression following global cerebral ischemia. Brain Res. Mol". Brain Res. 95 ... and there may be an increase in expression of the anti-apoptotic protein BCl-2. Many physicians over the centuries have tried ... "Induction of apoptosis in fibroblasts by c-myc protein". Cell. 69 (1): 119-28. doi:10.1016/0092-8674(92)90123-T. PMID 1555236. ...

*SNCAIP

"Lack of binding observed between human alpha-synuclein and Bcl-2 protein family". Neurosci. Lett. 316 (2): 103-7. doi:10.1016/ ... alpha interacting protein (synphilin), and SYPH1. This gene encodes a protein containing several protein-protein interaction ... 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 ...

*BCL3

"Signal-dependent translation of a regulatory protein, Bcl-3, in activated human platelets". Proc. Natl. Acad. Sci. U.S.A. 95 ( ... B-cell lymphoma 3-encoded protein is a protein that in humans is encoded by the BCL3 gene. This gene is a proto-oncogene ... Na SY, Choi JE, Kim HJ, Jhun BH, Lee YC, Lee JW (Oct 1999). "Bcl3, an IkappaB protein, stimulates activating protein-1 ... Na SY, Choi JE, Kim HJ, Jhun BH, Lee YC, Lee JW (October 1999). "Bcl3, an IkappaB protein, stimulates activating protein-1 ...

*BCL2-like 1 (gene)

... 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 ... a Bcl-2/Bcl-XL- and procaspase-8-associated protein in the endoplasmic reticulum". The Journal of Cell Biology. 139 (2): 327-38 ...

*DLC1

... also performs a second pro-apoptotic function: it reduces cellular levels of the anti-apoptotic protein Bcl-2. ... In tumor cells which are not expressing DLC1, Bcl-2 levels remain high and the ratio of Bax/Bcl-2 low, so apoptosis is ... Deleted in Liver Cancer 1 also known as DLC1 and StAR-related lipid transfer protein 12 (STARD12) is a protein which in humans ... The SAM domain (stretching from amino acids 11-78) is believed to be involved in protein-protein interactions. The exact ...

*HK2

An alternative model proposes the opposite, that HK2 regulates binding of the anti-apoptotic protein Bcl-Xl to VDAC. In ... "A protein-protein interaction network for human inherited ataxias and disorders of Purkinje cell degeneration". Cell. 125 (4): ... "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173-8. doi:10.1038/ ... HK2 gene expression is regulated by a phosphatidylinositol 3-kinaselp70 S6 protein kinase-dependent pathway and can be induced ...

*PAX7

Margue CM, Bernasconi M, Barr FG, Schäfer BW (June 2000). "Transcriptional modulation of the anti-apoptotic protein BCL-XL by ... Paired box protein Pax-7 is a protein that in humans is encoded by the PAX7 gene. Pax-7 plays a role in neural crest ... PAX7 protein, human at the US National Library of Medicine Medical Subject Headings (MeSH) PAX7 human gene location in the UCSC ... Vorobyov E, Horst J (November 2004). "Expression of two protein isoforms of PAX7 is controlled by competing cleavage- ...

*Erythropoietin receptor

... induces the transcription of pro-survival protein Bcl-xL. Additionally, EpoR has been implicated in suppressing expression of ... Feng GS, Ouyang YB, Hu DP, Shi ZQ, Gentz R, Ni J (May 1996). "Grap is a novel SH3-SH2-SH3 adaptor protein that couples tyrosine ... The erythropoietin receptor (EpoR) is a protein that in humans is encoded by the EPOR gene. EpoR is a 52kDa peptide with a ... a direct role for Stat5 in Bcl-X(L) induction". Cell. 98 (2): 181-91. doi:10.1016/S0092-8674(00)81013-2. PMID 10428030. De ...

*FKBP8

"Molecular characterization of FK-506 binding protein 38 and its potential regulatory role on the anti-apoptotic protein Bcl-2 ... FK506-binding protein 8 is a protein that in humans is encoded by the FKBP8 gene. The protein encoded by this gene is a member ... 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173-8. doi:10.1038 ... "The flexible loop of Bcl-2 is required for molecular interaction with immunosuppressant FK-506 binding protein 38 (FKBP38)". ...

*Phorbol-12-myristate-13-acetate-induced protein 1

Noxa has been shown to interact with: BCL2-like 1, Bcl-2, and MCL1. Apoptosis Apoptosome Bcl-2 Bcl-2-associated X protein (BAX ... Noxa (Latin for damage) is a pro-apoptotic member of the Bcl-2 protein family. Bcl-2 family members can form hetero- or ... Phorbol-12-myristate-13-acetate-induced protein 1 is a protein that in humans is encoded by the PMAIP1 gene, and is also known ... "Proapoptotic Bak is sequestered by Mcl-1 and Bcl-xL, but not Bcl-2, until displaced by BH3-only proteins". Genes Dev. 19 (11): ...

*BCL2L2

Bcl-2-like protein 2 is a protein that in humans is encoded by the BCL2L2 gene. It was originally discovered by Leonie Gibson, ... Ayllón V, Cayla X, García A, Fleischer A, Rebollo A (July 2002). "The anti-apoptotic molecules Bcl-xL and Bcl-w target protein ... 2002). "The anti-apoptotic molecules Bcl-xL and Bcl-w target protein phosphatase 1alpha to Bad". Eur. J. Immunol. 32 (7): 1847- ... is an ovarian BH3 domain-containing proapoptotic Bcl-2 protein capable of dimerization with diverse antiapoptotic Bcl-2 members ...

*Repinotan

In addition, the protein Bcl-2, the serotonergic glial growth factor S-100beta, and Nerve Growth Factor are affected by ... "The G protein-coupled 5-HT1A receptor causes suppression of caspase-3 through MAPK and protein kinase Calpha". Biochimica et ... When repinotan first binds to both pre- and post-synaptic 5-HT1A receptors, G protein-coupled inwardly rectifying K+ channels ...

*Adenovirus genome

Control protein E1B 19K suppresses apoptosis by mimicking the action of cellular protein Bcl-2. Control protein E1B 55K binds ... Membrane protein E3 RID-alpha and membrane protein E3 RID-beta performs a variety of molecular functions that contribute to ... "PHA3615: E3 gp19K protein". NCBI. Retrieved 2013-01-17. "PHA3613: E3 14.7K protein". NCBI. Retrieved 2013-01-17. "PHA3605: ... and the terminal protein TP. Encapsidation proteins IVa2, 52K, and L1, and hexon assembly protein 100K are involved in assembly ...

*BCL2L13

... such as Bcl-rambo beta. As a member of the Bcl-2 protein family, Bcl-rambo comprises four conserved BH domains and a ... Bcl-rambo is a member of the Bcl-2 family of proteins that regulate apoptosis. In cells, Bcl-rambo is localized to the ... This gene encodes a mitochondrially-localized protein which is classified under the Bcl-2 protein family. Overexpression of the ... An alternatively-spliced protein variant, called Bcl-rambo beta, is composed of only the BH4 domain, completely lacking the BH ...

*NF-κB

Although the IκB family consists of IκBα, IκBβ, IκBε, and Bcl-3, the best-studied and major IκB protein is IκBα. Due to the ... In addition, p50 and p52 homodimers also bind to the nuclear protein Bcl-3, and such complexes can function as transcriptional ... Concerning known protein inhibitors of NF-κB activity, one of them is IFRD1, which represses the activity of NF-κB p65 by ... The circumsporozoite protein of Plasmodium falciparum has been shown to be an inhibitor of NF-κB. Aberrant activation of NF-κB ...

*BOK (gene)

Bok (Bcl-2 related ovarian killer) is a protein-coding gene of the Bcl-2 family that is found in many invertebrates and ... Bok mRNA comprises five exons which code for a 213 amino acid protein, called Bok-L. This protein consists of four Bcl-2 ... In 1997, the protein Bcl-2-related ovarian killer (Bok) was identified in a yeast two-hybrid experiment with a rat ovarian cDNA ... interactions with other anti-apoptotic proteins such as Bcl-2, Bcl-xL, and Bcl-w were not detectable (1). Later studies aimed ...

*Bcl-2

This is the first FDA approval of a protein-protein inhibitor of BCL-2. Bcl-2 has been shown to interact with: BAK1, BCAP31, ... Apoptosis Apoptosome Bcl-2 homologous antagonist killer (BAK) Bcl-2-associated X protein (BAX) Bcl-xL BH3 interacting domain ... The Bcl-2 Family Database The Bcl-2 Family at celldeath.de Bcl-2 publications sorted by impact at caspases.org bcl-2 Genes at ... ABT-737 is superior to previous BCL-2 inhibitors given its higher affinity for Bcl-2, Bcl-xL and Bcl-w. In vitro studies showed ...

*MCL1

... is an ovarian BH3 domain-containing proapoptotic Bcl-2 protein capable of dimerization with diverse antiapoptotic Bcl-2 members ... 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. ... one of the bcl-2 protein family". J. Biochem. 128 (3): 399-405. doi:10.1093/oxfordjournals.jbchem.a022767. PMID 10965038. ...

*DAD1

... one of the bcl-2 protein family". J. Biochem. 128 (3): 399-405. doi:10.1093/oxfordjournals.jbchem.a022767. PMID 10965038. Yulug ... one of the bcl-2 protein family". J. Biochem. 128 (3): 399-405. doi:10.1093/oxfordjournals.jbchem.a022767. PMID 10965038. ... Dolichyl-diphosphooligosaccharide-protein glycosyltransferase subunit DAD1 is an enzyme that in humans is encoded by the DAD1 ... The DAD1 protein disappeared in temperature-sensitive cells following a shift to the nonpermissive temperature, suggesting that ...

*Olfactory tubercle

... contribution of new neurons to the olfactory tubercle and involvement of the antiapoptotic protein bcl-2". Eur. J. Neurosci. 16 ...

*HuaChanSu

More specifically, these molecules suppress the protein Bcl-2, which is a cancer-prone lymphoma protein, and induce cell death ...

*Mitochondrial ribosomal protein L41

2005). "BMRP is a Bcl-2 binding protein that induces apoptosis". J. Cell. Biochem. 94 (3): 611-26. doi:10.1002/jcb.20292. PMID ... 39S ribosomal protein L41, mitochondrial is a protein that in humans is encoded by the MRPL41 gene. Mammalian mitochondrial ... This gene encodes a 39S subunit protein that belongs to the YmL27 ribosomal protein family. GRCh38: Ensembl release 89: ... 2005). "Mitochondrial ribosomal protein L41 suppresses cell growth in association with p53 and p27Kip1". Mol. Cell. Biol. 25 ( ...

*Caspase-activated DNase

2007). "Large-scale mapping of human protein-protein interactions by mass spectrometry". Molecular Systems Biology. 3 (1): 89. ... "Apoptosis initiated by Bcl-2-regulated caspase activation independently of the cytochrome c/Apaf-1/caspase-9 apoptosome". ... The protein caspase DNase is an endonuclease involved in the cell apoptotic process that facilitates the DNA breakup. Cell ... Later, it was found out that the way how this protein induces the DNA breakup is explained by its forms CAD and ICAD, which ...
PIM1_HUMAN] Proto-oncogene with serine/threonine kinase activity involved in cell survival and cell proliferation and thus providing a selective advantage in tumorigenesis. Exerts its oncogenic activity through: the regulation of MYC transcriptional activity, the regulation of cell cycle progression and by phosphorylation and inhibition of proapoptotic proteins (BAD, MAP3K5, FOXO3). Phosphorylation of MYC leads to an increase of MYC protein stability and thereby an increase of transcriptional activity. The stabilization of MYC exerted by PIM1 might explain partly the strong synergism between these two oncogenes in tumorigenesis. Mediates survival signaling through phosphorylation of BAD, which induces release of the anti-apoptotic protein Bcl-X(L)/BCL2L1. Phosphorylation of MAP3K5, an other proapoptotic protein, by PIM1, significantly decreases MAP3K5 kinase activity and inhibits MAP3K5-mediated phosphorylation of JNK and JNK/p38MAPK subsequently reducing caspase-3 activation and cell apoptosis. ...
Purpose: Chronic lymphocytic leukemia cells in lymph nodes (LNs), from which relapses are postulated to originate, display an anti-apoptotic profile in contrast to CLL cells from peripheral blood (PB). The BH3 mimetic ABT-737 antagonizes the anti-apoptotic proteins Bcl-XL and Bcl-2, but not Mcl-1 or Bfl-1. Previously, it was shown that CD40-stimulated CLL cells were resistant to ABT-737. We aimed to define which anti-apoptotic proteins determine resistance to ABT-737 in CLL and whether combination of known anti-leukemia drugs and ABT-737 was able to induce apoptosis of CD40-stimulated CLL cells. Experimental Design: To mimic the LN microenvironment, PB lymphocytes of CLL patients were cultured on feeder cells expressing CD40L and treated with ABT-737 with or without various drugs. In addition, we performed overexpression or knockdown of pro- and anti-apoptotic proteins in immortalized primary B cells. Results: Upon CD40-stimulation patient-specific variations in ABT-737 sensitivity correlated ...
Bcl-2 protein family members are central regulators of apoptosis with mitochondrial sites of action. Treatment-refractory cancers from a variety of sites display high expression of the pro-survival Bcl-XL factor. The Bcl-XL inhibitor 2-methoxy antimycin (2-MeAA) is a promising anticancer agent that kills multidrug-resistant tumor cells with high Bcl-XL expression. The selectivity of targeted therapies for tumor cells versus normal cells is often described as a consequence of tumor cell addiction to the targeted activity (e.g. EGFR antagonists). Bcl-XL expression modifies carbon metabolic flux in several cellular contexts. In the case of Bcl-XL, I propose that the molecular basis of "target addiction" is the superposition of a Bcl-XL metabolic function on the different metabolic states characteristic of tumor and normal cells. The primary aim of this project is to test the hypothesis that metabolic profiles of cancer cells and normal cells are modified by Bcl-XL expression in different ways, and ...
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 ...
Proapoptotic and antiapoptotic proteins in the Bcl family are key regulators of programmed cell death. It is the interaction between these molecules that determines cellular response to apoptotic signals, making them attractive targets for therapeutic intervention. In recent experiments designed to study tumor angiogenesis, Bcl-2 upregulation in endothelial cells was shown to be a critical mediator of vascular development. In this article, we develop a mathematical model that explicitly incorporates the response of endothelial cells to variations in proapoptotic and antiapoptotic proteins in the Bcl family, as well as the administration of specific antiangiogenic therapies targeted against Bcl-2. The model is validated by comparing its predictions to in vitro experimental data that reports microvessel density prior to and following the administration of 0.05 to 5.0 μmol/L of BL193, a promising small molecule inhibitor of Bcl-2. Numerical simulations of in vivo treatment of tumors predict the ...
A-371191 is a novel Bcl-XL antagonist. Bcl-XL is one of the anti-apoptotic Bcl-2 family members that plays a key role in the regulation of apoptosis. Overexpression of Bcl-XL occurs in numerous cancers and its overexpression correlates with increased resistance to many chemocytotoxic drugs.
If you know of any papers that use this antibody, please contact us at antibodies [at] alzforum [dot] org for consideration in the References section.. ...
The present study provides evidence demonstrating that chemoresistance and Fas resistance in B-NHL cell lines are commonly regulated by constitutive NF-κB activation. However, downstream of NF-κB, chemoresistance and Fas resistance are differentially regulated by Bcl-xL and YY1, respectively. Rituximab-mediated inhibition of NF-κB activity resulted in both the inhibition of Bcl-xL expression and chemosensitization and the inhibition of the transcription repressor YY1 and sensitization to CH-11-induced apoptosis. These differentially regulated mechanisms for chemo- and CH-11-induced apoptosis emanated from findings making use of both biologically engineered cell lines and specific chemical inhibitors. Treatment with rituximab or specific inhibitors of NF-κB sensitized NHL cells to both drug- and CH-11-induced apoptosis. The role of Bcl-xL expression in the regulation of drug resistance, but not Fas resistance, was demonstrated by the failure of rituximab to sensitize Bcl-xL-overexpressing ...
cansSAR 3D Structure of 3VBV | EXPLOITATION OF HYDROGEN BONDING CONSTRAINTS AND FLAT HYDROPHOBIC ENERGY LANDSCAPES IN PIM-1 KINASE NEEDLE SCREENING AND INHIBITOR DESIGN | 3VBV_A | Serine/threonine-protein kinase pim-1 - Also known as PIM1_HUMAN, PIM1. Proto-oncogene with serine/threonine kinase activity involved in cell survival and cell proliferation and thus providing a selective advantage in tumorigenesis. Exerts its oncogenic activity through: the regulation of MYC transcriptional activity, the regulation of cell cycle progression and by phosphorylation and inhibition of proapoptotic proteins (BAD, MAP3K5, FOXO3). Phosphorylation of MYC leads to an increase of MYC protein stability and thereby an increase of transcriptional activity. The stabilization of MYC exerted by PIM1 might explain partly the strong synergism between these two oncogenes in tumorigenesis. Mediates survival signaling through phosphorylation of BAD, which induces release of the anti-apoptotic protein Bcl-X(L)/BCL2L1.
Fucoidan, a fucose-rich polysaccharide isolated from brown alga, is currently under investigation as a new anti-cancer compound. In the present study, fucoidan extract (FE) from Cladosiphon navae-caledoniae Kylin was prepared by enzymatic digestion. We investigated whether a combination of FE with cisplatin, tamoxifen or paclitaxel had the potential to improve the therapeutic efficacy of cancer treatment. These co-treatments significantly induced cell growth inhibition, apoptosis, as well as cell cycle modifications in MDA-MB-231 and MCF-7 cells. FE enhanced apoptosis in cancer cells that responded to treatment with three chemotherapeutic drugs with downregulation of the anti-apoptotic proteins Bcl-xL and Mcl-1. The combination treatments led to an obvious decrease in the phosphorylation of ERK and Akt in MDA-MB-231 cells, but increased the phosphorylation of ERK in MCF-7 cells. In addition, we observed that combination treatments enhanced intracellular ROS levels and reduced glutathione (GSH) levels
The survival of T lymphocytes is tightly controlled during development. Here, we show that Bcl-xL, a protein homologue of Bcl-2, is highly regulated in the thymus in a pattern different than that of Bcl-2. The maximum expression was in CD4+CD8+ thymocytes, a developmental stage where Bcl-2 is downregulated. To assess the role of Bcl-xL in thymocyte apoptosis, we generated mice overexpressing an E mu-bcl-x transgene within the T cell compartment. Constitutive expression of Bcl-xL resulted in accumulation of thymocytes and mature T cells in lymphoid organs. Thymocytes overexpressing Bcl-xL exhibited increased viability in vitro and were resistant to apoptosis induced by different signals, including glucocorticoid, gamma irradiation, calcium ionophore, and CD3 cross-linking. However, Bcl-xL was unable to block clonal deletion of thymocytes reactive with self-superantigens or H-Y antigen. These studies demonstrate that Bcl-2 and Bcl-xL, two functionally related proteins, are regulated independently ...
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. ...
Mantle cell lymphoma (MCL) is characterized by a profound deregulation of the mechanisms controlling cell-cycle progression and survival. We herein show that the combination of 9-cis-retinoic acid (RA) and IFN-α induces marked antiproliferative and proapoptotic effects in MCL cells through the modulation of critical targets. Particularly, IFN-α enhances RA-mediated G0-G1 cell accumulation by downregulating cyclin D1 and increasing p27Kip1 and p21WAF1/Cip1 protein levels. Furthermore, RA/IFN-α combination also induces apoptosis by triggering both caspases-8 and -9 resulting in Bax and Bak activation. In particular, RA/IFN-α treatment downregulates the antiapoptotic Bcl-xL and Bfl-1 proteins and upregulates the proapoptotic BH3-only Noxa protein. Sequestration of Mcl-1 and Bfl-1 by upregulated Noxa results in the activation of Bid, and the consequent induction of apoptosis is inhibited by Noxa silencing. Noxa upregulation is associated with nuclear translocation of the FOXO3a transcription ...
Journal of Immunology Research is a peer-reviewed, Open Access journal that provides a platform for scientists and clinicians working in different areas of immunology and therapy. The journal publishes research articles, review articles, as well as clinical studies related to classical immunology, molecular immunology, clinical immunology, cancer immunology, transplantation immunology, immune pathology, immunodeficiency, autoimmune diseases, immune disorders, and immunotherapy.
In light of the detrimental effect of normal Bcl-xL levels in terms of tumor growth, we wanted to carefully assess the proteins beneficial effect, its ability to deal with typical cellular toxins," Weintraub says.. The research team looked at sets of the same type of mice as in the previous experiments, this time examining liver cell damage resulting from a regimen that mimicked a three-day alcoholic binge. In this case, wild-type mice fared better than transgenic mice. Transgenic mice showed higher serum levels of a marker for liver injury and greater evidence of damage in tissue examined microscopically.. Bcl-xLs broader potential for protecting the liver became apparent in experiments that measured the effect of TNF-alpha, an immune-system substance that plays a role in development of a wide variety of liver disorders. TNF-alpha induced severe liver damage in the transgenic, Bcl-xL-impaired mice but not in the wild-type mice.. "The human Bcl-xL protein is functionally identical to the mouse ...
The first fragment-derived drug approved, vemurafenib, illustrated how quickly FBDD could move: just six years from the start of the program to approval. In contrast, venetoclax is the culmination of a program that has been running for more than two decades; Steve Fesik and his colleagues at Abbott published the X-ray and NMR structure of the protein BCL-xL back in 1996! The original SAR by NMR work was done on this protein, leading to ABT-263, which hits both BCL-xL and BCL-2. Subsequent work revealed that a selective BCL-2 inhibitor might be preferable in some cases, and further medicinal chemistry led to venetoclax ...
A-1331852 is a potent and BCL-XL-selective inhibitor. BCL-XL is the major antiapoptotic survival protein and may be a novel therapeutic target in CML. BCL-XL-selective inhibitors have the potential to enhance the efficacy of docetaxel in solid tumors and avoid the exacerbation of neutropenia observed with navitoclax. A-1331852 may have potential as improved cancer therapeutics.
To assess the role of BAX in drug-induced apoptosis in human colorectal cancer cells, we generated cells that lack functional BAX genes. Such cells were partially resistant to the apoptotic effects of the chemotherapeutic agent 5-fluorouracil, but apoptosis was not abolished. In contrast, the absence of BAX completely abolished the apoptotic response to the chemopreventive agent sulindac and other nonsteroidal anti-inflammatory drugs (NSAIDs). NSAIDs inhibited the expression of the antiapoptotic protein Bcl-XL, resulting in an altered ratio of BAX to Bcl-XL and subsequent mitochondria-mediated cell death. These results establish an unambiguous role forBAX in apoptotic processes in human epithelial cancers and may have implications for cancer chemoprevention strategies. ...
Vesicular stomatitis virus (VSV) is a potential oncolytic virus for treating glioblastoma multiforme (GBM), an aggressive brain tumor. Matrix (M) protein mutants of VSV have shown greater selectivity for killing GBM cells versus normal brain cells than VSV with wild-type M protein. The goal of this research was to determine the contribution of death receptor and mitochondrial pathways to apoptosis induced by an M protein mutant (M51R) VSV in U87 human GBM tumor cells. Compared to controls, U87 cells expressing a dominant negative form of Fas (dnFas) or overexpressing Bcl-XL had reduced caspase-3 activation following infection with M51R VSV, indicating that both the death receptor pathway and mitochondrial pathways are important for M51R VSV-induced apoptosis. Death receptor signaling has been classified as type I or type II, depending on whether signaling is independent (type I) or dependent on the mitochondrial pathway (type II). Bcl-XL overexpression inhibited caspase activation in response to ...
Bcl-xL is a member of the Bcl-2 family of apoptotic regulators, responsible for inhibiting the permeabilization of the mitochondrial outer membrane, and a promising anti-cancer target. Bcl-xL exists in the following conformations, each believed to play a role in the inhibition of apoptosis: (a) a soluble folded conformation, (b) a membrane-anchored (by its C-terminal α8 helix) form, which retains the same fold as in solution and (c) refolded membrane-inserted conformations, for which no structural data are available. Previous studies established that in the cell Bcl-xL exists in a dynamic equilibrium between soluble and membranous states, however, no direct evidence exists in support of either anchored or inserted conformation of the membranous state in vivo. In this in vitro study, we employed a combination of fluorescence and EPR spectroscopy to characterize structural features of the bilayer-inserted conformation of Bcl-xL and the lipid modulation of its membrane insertion transition. Our ...
Forms homodimers, and heterodimers with BAX, BAD, BAK and Bcl-X(L). Heterodimerization with BAX requires intact BH1 and BH2 motifs, and is necessary for anti-apoptotic activity (PubMed:8183370). Interacts with EI24 (By similarity). Also interacts with APAF1, BBC3, BCL2L1, BNIPL, MRPL41 and TP53BP2. Binding to FKBP8 seems to target BCL2 to the mitochondria and probably interferes with the binding of BCL2 to its targets. Interacts with BAG1 in an ATP-dependent manner. Interacts with RAF1 (the Ser-338 and Ser-339 phosphorylated form). Interacts (via the BH4 domain) with EGLN3; the interaction prevents the formation of the BAX-BCL2 complex and inhibits the anti-apoptotic activity of BCL2. Interacts with G0S2; this interaction also prevents the formation of the anti-apoptotic BAX-BCL2 complex. Interacts with RTL10/BOP. Interacts with the SCF(FBXO10) complex. Interacts (via the loop between motifs BH4 and BH3) with NLRP1 (via LRR repeats), but not with NLRP2, NLRP3, NLRP4, PYCARD, nor MEFV ...
Bcl-2-like 8, 0.1 mg. Bad is a member of the Bcl2 family and acts to promote apoptosis by forming heterodimers with the survival proteins Bcl2 and BclxL, thus preventing them from binding with BAX.
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The BH3-mimetic ABT-737 and an orally bioavailable compound of the same class, navitoclax (ABT-263), have shown promising antitumor efficacy in preclinical and early clinical studies. Although both drugs avidly bind Bcl-2, Bcl-xL, and Bcl-w in vitro, we find that Bcl-2 is the critical target in vivo, suggesting that patients with tumors overexpressing Bcl-2 will probably benefit. In human non-Hodgkin lymphomas, high expression of Bcl-2 but not Bcl-xL predicted sensitivity to ABT-263. Moreover, we show that increasing Bcl-2 sensitized normal and transformed lymphoid cells to ABT-737 by elevating proapoptotic Bim. In striking contrast, increasing Bcl-xL or Bcl-w conferred robust resistance to ABT-737, despite also increasing Bim. Cell-based protein redistribution assays unexpectedly revealed that ABT-737 disrupts Bcl-2/Bim complexes more readily than Bcl-xL/Bim or Bcl-w/Bim complexes. These results have profound implications for how BH3-mimetics induce apoptosis and how the use of these compounds ...
TY - JOUR. T1 - The N-terminal helix of Bcl-xL targets mitochondria. AU - McNally, Melanie A.. AU - Soane, Lucian. AU - Roelofs, Brian A.. AU - Hartman, Adam L.. AU - Hardwick, J Marie. PY - 2013/3. Y1 - 2013/3. N2 - Anti- and pro-apoptotic Bcl-2 family members regulate the mitochondrial phase of apoptotic cell death. The mitochondrial targeting mechanisms of Bcl-2 family proteins are tightly regulated. Known outer mitochondrial membrane targeting sequences include the C-terminal tail and central helical hairpin. Bcl-xL also localizes to the inner mitochondrial membrane, but these targeting sequences are unknown. Here we investigate the possibility that the N-terminus of Bcl-xL also contains mitochondrial targeting information. Amino acid residues 1-28 of Bcl-xL fused to EGFP are sufficient to target mitochondria. Although positive charges and helical propensity are required for targeting, similar to import sequences the N-terminus is not sufficient for efficient mitochondrial import.. AB - ...
bcl-x is a member of the bcl-2 gene family, which may regulate programmed cell death. Mice were generated that lacked Bcl-x. The Bcl-x-deficient mice died around embryonic day 13. Extensive apoptotic cell death was evident in postmitotic immature neurons of the developing brain, spinal cord, and dorsal root ganglia. Hematopoietic cells in the liver were also apoptotic. Analyses of bcl-x double-knockout chimeric mice showed that the maturation of Bcl-x-deficient lymphocytes was diminished. The life-span of immature lymphocytes, but not mature lymphocytes, was shortened. Thus, Bcl-x functions to support the viability of immature cells during the development of the nervous and hematopoietic systems. ...
Impaired apoptosis contributes to cancer development and resistance towards chemotherapy, since apoptosis normally eliminates cells with damaged DNA or increased malignant potential. The increased resistance towards cell death often limits therapeutic options in the clinic and is one major problemin current tumor therapy. Different approaches, which have been described so far intend to lower the apoptotic threshold in order to eliminate chemoresistant cancer cells. In the first part of this thesis the anti-tumor potential of the bispecific 4625 oligonucleotide was investigated in combination with chemotherapeutic drugs in vitro and in vivo. The second part describes the anti tumor activity of the recombinant Ep-CAM specific scFv immunotoxin 4D5MOC-B-ETA in vitro and in nude mice. Bcl-2 and Bcl-xL are inhibitors of apoptosis frequently overexpressed in malignant tumor cells. Downregulation of either Bcl-2 or Bcl-xL lowers the apoptotic threshold and tumor cells undergo apoptosis. The 4625 ...
Impaired apoptosis contributes to cancer development and resistance towards chemotherapy, since apoptosis normally eliminates cells with damaged DNA or increased malignant potential. The increased resistance towards cell death often limits therapeutic options in the clinic and is one major problemin current tumor therapy. Different approaches, which have been described so far intend to lower the apoptotic threshold in order to eliminate chemoresistant cancer cells. In the first part of this thesis the anti-tumor potential of the bispecific 4625 oligonucleotide was investigated in combination with chemotherapeutic drugs in vitro and in vivo. The second part describes the anti tumor activity of the recombinant Ep-CAM specific scFv immunotoxin 4D5MOC-B-ETA in vitro and in nude mice. Bcl-2 and Bcl-xL are inhibitors of apoptosis frequently overexpressed in malignant tumor cells. Downregulation of either Bcl-2 or Bcl-xL lowers the apoptotic threshold and tumor cells undergo apoptosis. The 4625 ...
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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 ...
Expression of BCL2L1 (Bcl-X, bcl-xL, bcl-xS, BCL2L, BCLX, PPP1R52) in lymph node tissue. Antibody staining with HPA035734 in immunohistochemistry.
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Hepatocyte growth factor (HGF) is a cytokine with pleiotropic functions during wound healing and repair. Its anti-fibrotic effects were shown in animal models of lung fibrosis and linked to improved cellular survival and proliferation and reduced myofibroblast accumulation. HGF-elicited, pro-survival pathways have yet not been investigated in detail in lung epithelial cells. Based on literature, our study is focused on Bcl-xL, prosurvival protein involved in mitochondrial control of apoptosis.. Results: Western blot analysis of IPF lung homogenates revealed significantly increased expression of Bcl-xL when compared to donor lungs, and a similar observation was made in bleomycin versus saline treated murine lungs. In human IPF, much less in donor lungs, Bcl-xL protein is highly expressed in hyperplastic alveolar epithelial type II cells, basal cells, bronchial epithelial ciliated and non-ciliated cells. Furthermore, Bcl-xL expression co-localized with specific HGF receptor cMet. In vitro data ...
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). ...
B-cell lymphoma 2 (Bcl-2) family proteins are established regulators of cell survival, but their involvement in the normal function of primary cells has only recently begun to receive attention. In this study, we demonstrate that chemical and genetic loss-of-function of antiapoptotic Bcl-2 and Bcl-x(L) significantly augments glucose-dependent metabolic and Ca(2+) signals in primary pancreatic β-cells. Antagonism of Bcl-2/Bcl-x(L) by two distinct small-molecule compounds rapidly hyperpolarized β-cell mitochondria, increased cytosolic Ca(2+), and stimulated insulin release via the ATP-dependent pathway in β-cell under substimulatory glucose conditions. Experiments with single and double Bax-Bak knockout β-cells established that this occurred independently of these proapoptotic binding partners. Pancreatic β-cells from Bcl-2(-/-) mice responded to glucose with significantly increased NAD(P)H levels and cytosolic Ca(2+) signals, as well as significantly augmented insulin secretion. Inducible ...
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 ...
Bcl-X (Apoptosis Marker) Antibody - Without BSA and Azide, Mouse Monoclonal Antibody [Clone 2H12 ] validated in WB, IHC-P, IF, FC (AH10725-100), Abgent
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/
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. ...
Apoptosis regulator BAX TranslationBlocker™ siRNA. Tested in Human samples. The only siRNA validated in protein knockdown with detailed protocols. From: $219.
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
Accelerates programmed cell death. Association to the apoptosis repressors Bcl-X(L), BHRF1, Bcl-2 or its adenovirus homolog E1B 19k protein suppresses this death-promoting activity. Does not interact with BAX.
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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 ...
Most studies looking at the expression of Bcl-2 in cholangiocarcinoma report varying amounts of Bcl-2 protein expression in this disease.24 In contrast, a study looking at Bcl-2 protein expression in cholangiocarcinoma recently reported that none of the cholangiocarcinoma samples examined expressed the Bcl-2 protein.36 With Bcl-2 expression detected in the internal positive controls and in regenerating intrahepatic ductular epithelium, an observation reported previously,37 our inability to detect the of Bcl-2 protein is unlikely to be a result of poor antigen retrieval or low Bcl-2 antibody activity. There have been suggestions that in some cell types a reciprocal expression of survival proteins Bcl-2 and Bcl-XL occurs. Considering there are still many unanswered questions about the cellular control and preference of expression of the different Bcl-2 genes, this might explain the differences in reported findings. It may be that as we learn more about these proteins, reasons for the differences ...
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 ...
PubMed comprises more than 30 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
Model for the inactivation of prosurvival Bcl-2-like proteins by the BH3-only proteins. It is proposed that prosurvival family members, like Bcl-w, normally b
Find and order matched antibody pairs and products like this BAD (phospho S134) & BAD Protein Phosphorylation Antibody... | Jetzt Produkt ABIN1340465 bestellen.
FACE Bad is an in cell Western method (cell based assay) that includes ELISA reagents and 2 antibodies to monitor levels of both native Bad protein and phospho Bad (S112), which has been activated by kinases (phosphorylation).
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。
The assistance of a qualified health care provider familiar with all dosage outlines, contraindications, and herb/drug interactions outlined in Healing Lyme, and familar with your personal health history and current symptoms is strongly suggested. Nothing in this column is intended to replace the expertise and care of a qualified health care practitioner. The material is intended for educational purposes only.. ...
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 ...
Ischemia-reperfusion injury is the tissue damage happened when blood supply returns to the tissue after a period of ischemia or shortage of oxygen. This brain injury initiates an inflammatory response involving the expression of adhesion molecules and cytokines. The aim of this study is investigating the effect of hydroalcoholic extract of Cyperus rotundus L. on the expression of the Bcl-x1 antiapoptotic gene in rats hippocampus tissue following global ischemic-reperfusion injury. In the present study, attempts were made to investigate the effect of hydroalcoholic extract of Cyprus rotundus L. on the expression of the Bcl-x1 antiapoptotic gene in rats hippocampus tissue following global ischemic-reperfusion. To this end, eighteen male Wistar rats (250-300 g body wt) were used in this study. The animals were divided into three classes, each including 6 rats, I: Control class without ischemia-reperfusion, II: Ischemia-reperfusion class that was subjected to all surgical procedures, III: extract ...
Hyperoxic acute lung injury (HALI) is characterized by a cell death response with features of apoptosis and necrosis that is inhibited by IL-11 and other interventions. We hypothesized that Bfl-1/A1, an antiapoptotic Bcl-2 protein, is a critical regulator of HALI and a mediator of IL-11-induced cytoprotection. To test this, we characterized the expression of A1 and the oxygen susceptibility of WT and IL-11 Tg(+) mice with normal and null A1 loci. In WT mice, 100% O2 caused TUNEL+ cell death, induction and activation of intrinsic and mitochondrial-death pathways, and alveolar protein leak. Bcl-2 and Bcl-xl were also induced as an apparent protective response. A1 was induced in hyperoxia, and in A1-null mice, the toxic effects of hyperoxia were exaggerated, Bcl-2 and Bcl-xl were not induced, and premature death was seen. In contrast, IL-11 stimulated A1, diminished the toxic effects of hyperoxia, stimulated Bcl-2 and Bcl-xl, and enhanced murine survival in 100% O2. In A1-null mice, IL-11-induced ...
Hyperoxic acute lung injury (HALI) is characterized by a cell death response with features of apoptosis and necrosis that is inhibited by IL-11 and other interventions. We hypothesized that Bfl-1/A1, an antiapoptotic Bcl-2 protein, is a critical regulator of HALI and a mediator of IL-11-induced cytoprotection. To test this, we characterized the expression of A1 and the oxygen susceptibility of WT and IL-11 Tg(+) mice with normal and null A1 loci. In WT mice, 100% O2 caused TUNEL+ cell death, induction and activation of intrinsic and mitochondrial-death pathways, and alveolar protein leak. Bcl-2 and Bcl-xl were also induced as an apparent protective response. A1 was induced in hyperoxia, and in A1-null mice, the toxic effects of hyperoxia were exaggerated, Bcl-2 and Bcl-xl were not induced, and premature death was seen. In contrast, IL-11 stimulated A1, diminished the toxic effects of hyperoxia, stimulated Bcl-2 and Bcl-xl, and enhanced murine survival in 100% O2. In A1-null mice, IL-11-induced ...
Hyperoxic acute lung injury (HALI) is characterized by a cell death response with features of apoptosis and necrosis that is inhibited by IL-11 and other interventions. We hypothesized that Bfl-1/A1, an antiapoptotic Bcl-2 protein, is a critical regulator of HALI and a mediator of IL-11-induced cytoprotection. To test this, we characterized the expression of A1 and the oxygen susceptibility of WT and IL-11 Tg(+) mice with normal and null A1 loci. In WT mice, 100% O2 caused TUNEL+ cell death, induction and activation of intrinsic and mitochondrial-death pathways, and alveolar protein leak. Bcl-2 and Bcl-xl were also induced as an apparent protective response. A1 was induced in hyperoxia, and in A1-null mice, the toxic effects of hyperoxia were exaggerated, Bcl-2 and Bcl-xl were not induced, and premature death was seen. In contrast, IL-11 stimulated A1, diminished the toxic effects of hyperoxia, stimulated Bcl-2 and Bcl-xl, and enhanced murine survival in 100% O2. In A1-null mice, IL-11-induced ...
Bad is a member of the BCL-2 family of regulators involved in programmed cell death. This protein positively regulates cell apoptosis by forming heterodimers with BCL-xL and BCL-2, and reversing their death repressor activity. Proapoptotic activity of this protein is regulated through its phosphorylation. Protein kinas
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。
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The four known human ANT isoforms (ANT1, ANT2, ANT3, and ANT4) exhibit tissue-, cell-type-, and developmental stage-specific expression patterns [18]. ANT1 is strongly expressed in terminally differentiated cells; ANT2 is overexpressed in tissues that have high proliferative ability and in several cancer cell lines [16, 21]; and ANT3 is ubiquitously expressed in all tissues. Whereas ANT1 and ANT3 exert pro-apoptotic effects when overexpressed, ANT2, instead, has an anti-apoptotic function [20, 28]. We previously observed that ANT2 is overexpressed in the breast cancer cell lines MCF7 and MDA-MB-231 but is absent from the non-neoplastic mammary epithelial cell line MCF10A [16]. Moreover, vector-based RNAi knockdown of ANT2 expression in MCF7 and MDA-MB-231 cells resulted in cell cycle arrest and apoptotic cell death; these events were accompanied by cellular energy (ATP) depletion, mitochondrial membrane depolarization, Bax induction, and Bcl-xL down-regulation [16]. TNF-α and TNF receptor I ...
OBJECTIVES: To evaluate the efficacy of combination of navitoclax, carboplatin and paclitaxel in ovarian cancer.. METHODS: 8 ovarian cancer cell lines were treated with either doublet or triplet combinations of navitoclax, carboplatin and paclitaxel. Interactions were assessed by determining a combination index or measuring caspase activity. The effect of the combinations was also evaluated by measuring the inhibition of cells grown as spheroids.. RESULTS: Navitoclax exhibited modest (IC(50)=3-8 μM) single agent potency. Antagonism between carboplatin and paclitaxel was evident in Ovcar-4, Ovcar-8 and Skov-3 cells. Drug combinations including navitoclax with carboplatin and/or paclitaxel showed significantly less antagonism, or even synergy, in several cell lines than carboplatin/paclitaxel alone. Navitoclax enhanced the activation of caspase 3/7 induced by carboplatin and/or paclitaxel in Igrov-1 cells. Combinations of navitoclax, carboplatin and paclitaxel showed more than additive activity ...
Bcl-xL is an antiapoptotic Bcl-2 family member that is required for embryonic development and can contribute to cancer cell survival (Letai, 2008; Hardwick and Youle, 2009). The traditional viewpoint is that anti- and proapoptotic Bcl-2 family proteins actively engage each other to determine cell fate after a death stimulus (Galonek and Hardwick, 2006; Youle and Strasser, 2008). The best-characterized cell survival activity of Bcl-xL is its ability to inhibit Bax-induced pores in the outer mitochondrial membrane (Billen et al., 2008). In this manner, Bcl-xL prevents release of mitochondrial cytochrome c into the cytoplasm, where cytochrome c induces apoptosome formation to trigger caspase-dependent death of mammalian cells. Attention has been focused on the functional interactions and the binding specificities between anti- and proapoptotic Bcl-2-related proteins, leading to new therapeutic strategies (Oltersdorf et al., 2005).. The evolutionary conservation of Bcl-2-like proteins cannot be ...
CCAR1; cell division cycle and apoptosis regulator 1; cell division cycle and apoptosis regulator protein 1; CARP 1; CARP1; FLJ10590; death inducer with SAP domain; cell cycle and apoptosis regulatory protein 1; MGC44628; RP11-437A18.1; novel protein similar to vertebrate cell division cycle and apoptosis regulator 1 (CCAR1 ...
Chronic lymphocytic leukemia (CLL) is the most common leukemia in adults. In recent years, it has become apparent that CLL is strongly dependent on its microenvironment for survival and proliferation. The pro-survival effect of the micro-environment is mainly mediated by upregulation of anti-apoptotic factors such as BCL-XL and MCL-1 upon receiving stimuli from surrounding T cells and macrophages.1 In addition to changes in expression of anti-apoptotic proteins, we and others have reported altered expression of BH3-only pro-apoptotic NOXA and BMF proteins.2,3 We have also found that the NOXA/MCL-1 balance in CLL cells is inverted in the lymph node compared to peripheral blood, which is indicative of an increase in chemoresistance.4,5. NOXA is a pro-apoptotic member of the BH3-only subfamily of Bcl-2 proteins, which also contains BID, BIM, BAD, and PUMA.6 In contrast to BIM or PUMA, genetic ablation of NOXA does not result in an overt phenotype.7 This is a reflection of the weak pro-apoptotic ...
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 ...
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 ...
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 ...
Conformational changes in inhibitory PAS domain protein associated with binding of HIF-1α and Bcl-xL in living cells.Conformational changes in inhibitory PAS domain protein associated with binding of HIF-1α and Bcl-xL in living cells. ...
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 ...
Here, we show that the BH3-only mimetic, ABT-737, has two properties: one, it can overcome resistance to immunotoxin-mediated apoptosis; and two, it can increase immunotoxin delivery from the ER to the cytosol resulting in enhanced killing by as much as 20-fold. Both activities were achieved using concentrations (3 or 10 μmol/L) of ABT-737 that were nontoxic when added alone. Combinations of immunotoxin and ABT-737 were effective at overcoming resistance because each agent targeted a distinct Bcl-2 family member. By inhibiting protein synthesis, immunotoxin treatment promotes a decline in Mcl-1 levels. This was reported previously for both cycloheximide (27) and PE immunotoxins (26), and was confirmed here. ABT-737 is a peptide mimetic modeled on a BH3-only domain and exhibits high binding affinity binding for Bcl-2, Bcl-xl, and Bcl-w (19). Binding of ABT-737 to either Bcl-2 or Bcl-xl neutralizes their prosurvival activity, allowing Bax or Bak to initiate the intrinsic arm of the apoptosis ...
FACE Bad is an in cell Western method (cell based assay) that includes ELISA reagents and 2 antibodies to monitor levels of both native Bad protein and phospho Bad (S112), which has been activated by kinases (phosphorylation).
Yo-yo dieting is the pattern of losing weight, regaining it and then dieting again. This article examines 10 reasons why yo-yo dieting is bad for you.
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Lenalidomide in heavily pretreated refractory diffuse large B-cell lymphoma: a case report | Journal of Medical Case Reports |...Lenalidomide in heavily pretreated refractory diffuse large B-cell lymphoma: a case report | Journal of Medical Case Reports |...

Strong expression of the Bcl-2 protein in the DLBCL infiltrate, objective magnification 40×. ... an E3 ubiquitin ligase complex co-receptor protein [29]. ...
more infohttps://jmedicalcasereports.biomedcentral.com/articles/10.1186/1752-1947-8-325

BCL-2 | protein | Britannica.comBCL-2 | protein | Britannica.com

... in mammals known as the BCL-2 protein family. This protein family, which provides the framework for controlling apoptosis, ... 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. This protein family, which provides the framework for controlling apoptosis, ... BCL-2, the first family member, forms the molecular basis for sustaining the lymphoma cancer cells. The BCL-2 family of ...
more infohttps://www.britannica.com/topic/BCL-2-protein

Recombinant Human Ctip1 / BCL-11A protein (ab112415) ReferencesRecombinant Human Ctip1 / BCL-11A protein (ab112415) References

BCL-11A protein (ab112415). Please let us know if you have used this product in your publication ...
more infohttps://www.abcam.com/recombinant-human-ctip1--bcl-11a-protein-ab112415-references.html

BCL-6 protein is expressed in germinal-center B cells.BCL-6 protein is expressed in germinal-center B cells.

... Cattoretti G., Chang C.C., Cechova K., Zhang J., Ye B.H., Falini B., ... The BCL-6 protein was also detectable in inter- and intra-follicular CD4+ T cells, but not in other follicular components ... Nucleotide sequencing of BCL-6 cDNA predicted a protein containing six zinc-finger domains, suggesting that it may function as ... Immunohistochemical analysis of DLCL and FL biopsy samples showed that the BCL-6 protein is detectable in these tumors ...
more infohttp://www.uniprot.org/citations/7795255

The Bcl-2 Protein Family: Arbiters of Cell Survival | ScienceThe Bcl-2 Protein Family: Arbiters of Cell Survival | Science

Thank you for your interest in spreading the word about Science.. NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.. ...
more infohttps://science.sciencemag.org/content/281/5381/1322.full

The BCL-2 protein family: opposing activities that mediate cell death.  - PubMed - NCBIThe BCL-2 protein family: opposing activities that mediate cell death. - PubMed - NCBI

The BCL-2 protein family: opposing activities that mediate cell death.. Youle RJ1, Strasser A. ... B-cell lymphoma 2 (Bcl-2) protein family - overview and references - Guide to Pharmacology ... BCL-2 family proteins, which have either pro- or anti-apoptotic activities, have been studied intensively for the past decade ... Although these insights into interactions among BCL-2 family proteins reveal how these proteins are regulated, a unifying ...
more infohttps://www.ncbi.nlm.nih.gov/pubmed/18097445?dopt=Abstract

Bcl-2 Protein Targeting by the p53/p21 Complex-Response | Cancer ResearchBcl-2 Protein Targeting by the p53/p21 Complex-Response | Cancer Research

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-2 protein targeting by the p53/p21 complex-letter. Cancer Res 2018;78:2770-1. ... Bcl-w promotes cell invasion by blocking the invasion-suppressing action of Bax. Cell Signal 2012;24:1163-72. ...
more infohttp://cancerres.aacrjournals.org/content/78/10/2772

Assessment of Dynamic BCL-2 Protein Shuttling Between Outer Mitochondrial Membrane and Cytosol | SpringerLinkAssessment of Dynamic BCL-2 Protein Shuttling Between Outer Mitochondrial Membrane and Cytosol | SpringerLink

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. ... Assessment of Dynamic BCL-2 Protein Shuttling Between Outer Mitochondrial Membrane and Cytosol. In: Gavathiotis E. (eds) BCL-2 ... The retrotranslocation of BCL-2 proteins from the OMM can be measured using fluorescence-labeled protein in intact cells or ...
more infohttps://link.springer.com/protocol/10.1007%2F978-1-4939-8861-7_10

The Bcl-2 Protein Family: Arbiters of Cell Survival | ScienceThe Bcl-2 Protein Family: Arbiters of Cell Survival | Science

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). ... Bcl-xL, Bcl-2, and Bax do form channels in lipid bilayers in vitro, and those created by Bax and Bcl-2 have distinct ... 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 ... right). Model for Apaf-1 regulation by the Bcl-2 family. Bcl-xL (or another pro-survival member) may bind Apaf-1 and prevent it ...
more infohttps://science.sciencemag.org/content/281/5381/1322?ijkey=ea8a22bcd0c68bdc498b9887f0db8f1a9def4d97&keytype2=tf_ipsecsha

apoptosis facilitator Bcl-2-like protein 14 [Mus musculus] - Protein - NCBIapoptosis facilitator Bcl-2-like protein 14 [Mus musculus] - Protein - NCBI

Bcl-2 family member Bcl-G is not a proapoptotic protein. [Cell Death Dis. 2012] Bcl-2 family member Bcl-G is not a proapoptotic ... apoptosis facilitator Bcl-2-like protein 14 [Mus musculus] apoptosis facilitator Bcl-2-like protein 14 [Mus musculus]. gi, ... 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 ...
more infohttps://www.ncbi.nlm.nih.gov/protein/NP_080054.1

Antibodies to bcl-2 Protein Family - Product Review 04 | acris-antibodies.comAntibodies to bcl-2 Protein Family - Product Review 04 | acris-antibodies.com

Available antibody panel to bcl-2 Protein Family Anti- bcl-2, bcl-x, Bcl-xL , Mcl-1, Bag-1, bax, bak, Blk, Bim, Bad, Bmf, NOXA ... Home » Reviews » Antibodies to bcl-2 Protein Family - Product Review 04 Antibodies to bcl-2 Protein Family - Product Review 04 ... Antibody Tools for Detection of bcl-2 Family Members. Antibody products for detection of many of the above listed bcl-2 family ... At least 15 Bcl-2 family members have been identified in mammalian cells and several others in viruses. All members possess at ...
more infohttps://www.acris-antibodies.com/reviews/antibodies-bcl-2-protein-family.htm?ab_ag_reactivity=Rt

Antibodies to bcl-2 Protein Family - Product Review 04 | acris-antibodies.comAntibodies to bcl-2 Protein Family - Product Review 04 | acris-antibodies.com

Available antibody panel to bcl-2 Protein Family Anti- bcl-2, bcl-x, Bcl-xL , Mcl-1, Bag-1, bax, bak, Blk, Bim, Bad, Bmf, NOXA ... Home » Reviews » Antibodies to bcl-2 Protein Family - Product Review 04 Antibodies to bcl-2 Protein Family - Product Review 04 ... Antibody Tools for Detection of bcl-2 Family Members. Antibody products for detection of many of the above listed bcl-2 family ... At least 15 Bcl-2 family members have been identified in mammalian cells and several others in viruses. All members possess at ...
more infohttps://www.acris-antibodies.com/reviews/antibodies-bcl-2-protein-family.htm?ab_ag_presentation=Aff+-+Purified&product_property=pSer70

Hepatocyte growth factor suppresses tumor cell apoptosis in nasopharyngeal carcinoma by upregulating Bcl-2 protein expression.Hepatocyte growth factor suppresses tumor cell apoptosis in nasopharyngeal carcinoma by upregulating Bcl-2 protein expression.

0/BAX protein, human; 0/HGF protein, human; 0/Proto-Oncogene Proteins c-bcl-2; 0/bcl-2-Associated X Protein; 67256-21-7/ ... Proto-Oncogene Proteins c-bcl-2 / metabolism*. Time Factors. Up-Regulation. Young Adult. bcl-2-Associated X Protein / ... Expression of HGF, Bcl-2 and Bax in tumor tissues was investigated by immunohistochemical staining, and the apoptotic index was ... HGF is a potent inhibitor of cell apoptosis in NPC by upregulating Bcl-2 through both autocrine and paracrine EBV-independent ...
more infohttp://www.biomedsearch.com/nih/Hepatocyte-growth-factor-suppresses-tumor/19625133.html

Bok is a pro-apoptotic Bcl-2 protein with restricted expression in reproductive tissues and heterodimerizes with selective anti...Bok is a pro-apoptotic Bcl-2 protein with restricted expression in reproductive tissues and heterodimerizes with selective anti...

We have identified a new pro-apoptotic Bcl-2-related protein Bok, based on its binding to an ovarian anti-apoptosis protein Mcl ... Bcl-xL, and Bcl-w. We further tested interactions between Bok and several pro-apoptotic Bcl-2 proteins (Fig. 2A). Of interest, ... Bcl-2, Bcl-xL, Mcl-1, Bcl-w, and Bfl-1/A1) and pro-apoptotic members (Bax, BAD, Bak, Bik, Hrk, and BID). Through ... Bcl-xL, Bcl-w, BAD, Bax, Bak, or Bik fused to the GAL4 binding domain. In addition, prominent growth of colonies expressing Bcl ...
more infohttps://www.pnas.org/content/94/23/12401?ijkey=a5b74572254f11824bd2f89f6a0a9e5b2deef6bd&keytype2=tf_ipsecsha

Bcl2l11 - Bcl-2-like protein 11 - Mus musculus (Mouse) - Bcl2l11 gene & proteinBcl2l11 - Bcl-2-like protein 11 - Mus musculus (Mouse) - Bcl2l11 gene & protein

View protein in InterPro. IPR014771. Apoptosis_Bim_N. IPR017288. Bcl-2-like_11. IPR015040. Bcl-x_interacting_BH3_dom. IPR036834 ... View protein in InterPro. IPR014771. Apoptosis_Bim_N. IPR017288. Bcl-2-like_11. IPR015040. Bcl-x_interacting_BH3_dom. IPR036834 ... Bcl-2-like protein 11Add BLAST. 196. Amino acid modifications. Feature key. Position(s). DescriptionActions. Graphical view. ... Cluster: Bcl-2-like protein 11. 3. O54918-3. Q3U7X3. UPI0003D738DF. Mus musculus (Mouse). 110. UniRef100_Q3U7X3. Cluster: BCL2- ...
more infohttp://www.uniprot.org/uniprot/O54918

The presence of human papillomavirus-16/-18 E6, p53, and Bcl-2 protein in cervicovaginal smears from patients with invasive...The presence of human papillomavirus-16/-18 E6, p53, and Bcl-2 protein in cervicovaginal smears from patients with invasive...

... for women positive for the E6 protein and 17 times higher (95% CI, 5.5-58.3) for women positive for the bcl-2 protein compared ... and Bcl-2 protein in cervicovaginal smears from patients with invasive cervical cancer.. M R Pillai, S Halabi, A McKalip, P G ... These findings indicate that: (a) the presence of the bcl-2 protein is strongly associated with the development of invasive ... The presence of human papillomavirus-16/-18 E6, p53, and Bcl-2 protein in cervicovaginal smears from patients with invasive ...
more infohttp://cebp.aacrjournals.org/content/5/5/329

AID 1263891 - Induction of apoptosis in human HepG2 cells assessed as reduction in Bcl-2 protein level incubated for 48 hrs by...AID 1263891 - Induction of apoptosis in human HepG2 cells assessed as reduction in Bcl-2 protein level incubated for 48 hrs by...

Induction of apoptosis in human HepG2 cells assessed as reduction in Bcl-2 protein level incubated for 48 hrs by Western blot ...
more infohttps://pubchem.ncbi.nlm.nih.gov/bioassay/1263891

Bcl-2-associated X protein - WikipediaBcl-2-associated X protein - Wikipedia

... also known as bcl-2-like protein 4, is a protein that in humans is encoded by the BAX gene. BAX is a member of the Bcl-2 gene ... Bcl-2-associated X protein has been shown to interact with: Bcl-2, BCL2L1, BCL2A1 SH3GLB1, SLC25A4, VDAC1, TCTP, YWHAQ, Bid, ... The BAX gene was the first identified pro-apoptotic member of the Bcl-2 protein family. Bcl-2 family members share one or more ... "Identification of the protein-protein contact site and interaction mode of human VDAC1 with Bcl-2 family proteins". Biochem. ...
more infohttps://en.wikipedia.org/wiki/Bcl-2-associated_X_protein

RCSB PDB - Protein Feature View 









 - Bcl-2-interacting killer - Q13323 (BIK HUMAN)RCSB PDB - Protein Feature View - Bcl-2-interacting killer - Q13323 (BIK HUMAN)

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 ... Protein disorder predictions are based on JRONN (Troshin, P. and Barton, G. J. unpublished), a Java implementation of RONN * ...
more infohttp://www.rcsb.org/pdb/protein/Q13323

Biochemical and structural studies on the molecular interaction between P53 transcriptional activation domain and anti...Biochemical and structural studies on the molecular interaction between P53 transcriptional activation domain and anti...

... structural studies on the molecular interaction between P53 transcriptional activation domain and anti-apoptotic protein BCL-XL ... The p53/Bcl-2 and p53/Bcl-XL interaction were then investigated by different groups. The DNS binding domain of p53 was believed ... In this study, we identified a novel binding site on p53 N-terminal domain (NTD) for Bcl-XL. The p53 NTD/ Bcl-XL complex was ... p53 is believed to be the most important tumor suppressor protein and abnormality of p53 causes cancers and many other diseases ...
more infohttps://dr.ntu.edu.sg/handle/10356/18852

Fas-mediated Apoptosis in Neuroblastoma Requires Mitochondrial Activation and Is Inhibited by FLICE Inhibitor Protein and bcl-2...Fas-mediated Apoptosis in Neuroblastoma Requires Mitochondrial Activation and Is Inhibited by FLICE Inhibitor Protein and bcl-2...

Fas-mediated Apoptosis in Neuroblastoma Requires Mitochondrial Activation and Is Inhibited by FLICE Inhibitor Protein and bcl-2 ... Fas-mediated Apoptosis in Neuroblastoma Requires Mitochondrial Activation and Is Inhibited by FLICE Inhibitor Protein and bcl-2 ... Fas-mediated Apoptosis in Neuroblastoma Requires Mitochondrial Activation and Is Inhibited by FLICE Inhibitor Protein and bcl-2 ... Fas-mediated Apoptosis in Neuroblastoma Requires Mitochondrial Activation and Is Inhibited by FLICE Inhibitor Protein and bcl-2 ...
more infohttp://cancerres.aacrjournals.org/content/61/12/4864

Combination of thiol antioxidant Silibinin with Brostallicin is associated with increase in the anti-apoptotic protein Bcl-2...Combination of thiol antioxidant Silibinin with Brostallicin is associated with increase in the anti-apoptotic protein Bcl-2...

The mechanism underlying the interaction involved the apoptotic pathway as we demonstrated an increase in Bcl-2 protein levels ... Combination of thiol antioxidant Silibinin with Brostallicin is associated with increase in the anti-apoptotic protein Bcl-2 ... Combination of thiol antioxidant Silibinin with Brostallicin is associated with increase in the anti-apoptotic protein Bcl-2 ...
more infohttps://scholarbank.nus.edu.sg/handle/10635/24056?mode=full

AID 1342855 - Fluorescence Polarisation Assay: The fluorescence polarisation tests were carried out on microplates (384 wells)....AID 1342855 - Fluorescence Polarisation Assay: The fluorescence polarisation tests were carried out on microplates (384 wells)....

The Bcl-2 protein, at a final concentration of 2.50A?10A inverted question mark8 M, is mixed with a fluorescent peptide ( ...
more infohttps://pubchem.ncbi.nlm.nih.gov/bioassay/1342855

RCSB PDB - 5WHH: Crystal Structure of Bcl-2-related protein A1 in complex with stapled peptide (AQ7)T(0EH)LRRFGD(MK8)INFRQ(NH2)RCSB PDB - 5WHH: Crystal Structure of Bcl-2-related protein A1 in complex with stapled peptide (AQ7)T(0EH)LRRFGD(MK8)INFRQ(NH2)

Crystal Structure of Bcl-2-related protein A1 in complex with stapled peptide (AQ7)T(0EH)LRRFGD(MK8)INFRQ(NH2). *DOI: 10.2210/ ... Whereas numerous structures of anti-apoptotic BCL-2 protein complexes with α-helical BH3 peptides have been reported, the ... Whereas numerous structures of anti-apoptotic BCL-2 protein complexes with α-helical BH3 peptides have been reported, the ... Protein Workshop , Ligand Explorer. Global Symmetry: Asymmetric - C1 Global Stoichiometry: Hetero 2-mer - A1B Find Similar ...
more infohttps://www.rcsb.org/structure/5WHH

CD44+ cancer cells express higher levels of the anti-apoptotic protein Bcl-2 in breast tumours | Cancer Immunology ResearchCD44+ cancer cells express higher levels of the anti-apoptotic protein Bcl-2 in breast tumours | Cancer Immunology Research

Expression of Bcl-2 in breast tumour cells. Immunohistochemistry was used to evaluate Bcl-2 expression. The pattern of Bcl-2 ... CD44+ cancer cells express higher levels of the anti-apoptotic protein Bcl-2 in breast tumours. Zahra Madjd, Ali Zare Mehrjerdi ... To our knowledge, this is the first study on the expression of Bcl-2 protein in tumourigenic breast cancer cells to look at ... Breast tumours that lack the anti-apoptotic protein Bcl-2 appear to have high rates of both cell proliferation and cell death ...
more infohttp://cancerimmunolres.aacrjournals.org/content/canimmarch/9/1/4
  • All members possess at least one of four conserved motifs known as Bcl-2 homology domains (BH1 to BH4). (acris-antibodies.com)
  • Bcl-2 family members share one or more of the four characteristic domains of homology entitled the Bcl-2 homology (BH) domains (named BH1, BH2, BH3 and BH4), and can form hetero- or homodimers. (wikipedia.org)
  • Molecular basis for Bcl-2 homology 3 domain recognition in the Bcl-2 protein family: identification of conserved hot spot interactions. (inserm.fr)
  • To elucidate the molecular basis of this recognition process, we used molecular dynamics simulations coupled with the Molecular Mechanics/Poisson-Boltzmann Surface Area approach to identify the amino acids that make significant energetic contributions to the binding free energy of four complexes formed between Bcl-xl and pro-apoptotic Bcl-2 homology 3 peptides. (inserm.fr)
  • 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)
  • BCL-2 , the first family member, forms the molecular basis for sustaining the lymphoma cancer cells. (britannica.com)
  • Structural alterations of the 5' noncoding region of the BCL-6 gene have been found in 40% of diffuse large cell lymphoma (DLCL) and 5% to 10% of follicular lymphomas (FL), suggesting that deregulated BCL-6 expression may play a role in lymphomagenesis. (uniprot.org)
  • The first mammalian regulator emerged when bcl-2 , the gene activated by chromosome translocation in human follicular lymphoma ( 6 ), was unexpectedly found to permit the survival of cytokine-dependent hematopoietic cells, in a quiescent state, in the absence of cytokine ( 7 ). (sciencemag.org)
  • The protooncogene Bcl-2 was isolated at the breakpoint of the t(14, 18) chromosomal translocation associated with follicular B-cell lymphoma ( 9 ). (pnas.org)
  • Using antisera raised against N- and C-terminal BCL-6 synthetic oligopeptides in immunoprecipitation, immunoblot, and immunocytochemical assays, this study identifies the BCL-6 gene product as a 95-kD nuclear protein. (uniprot.org)
  • Immunohistochemical analysis of DLCL and FL biopsy samples showed that the BCL-6 protein is detectable in these tumors independent of the presence of BCL-6 gene rearrangements. (uniprot.org)
  • These results indicate that the expression of the BCL-6 gene is specifically regulated during B-cell differentiation and suggest a role for BCL-6 in germinal center development or function. (uniprot.org)
  • See the other reference sequence protein isoform for the Bcl2l14 gene (NP_001342615.1). (nih.gov)
  • From a rat ovarian fusion cDNA library, we isolated a new pro-apoptotic Bcl-2 gene, Bcl-2-related ovarian killer (Bok). (pnas.org)
  • Recent studies demonstrated that another C. elegans gene, ced-4, or its mammalian homolog Apaf-1 can bridge between Bcl-2/ced-9 family members and caspases ( 7 , 8 ). (pnas.org)
  • p>Describes annotations that are concluded from looking at variations or changes in a gene product such as mutations or abnormal levels and includes techniques such as knockouts, overexpression, anti-sense experiments and use of specific protein inhibitors. (uniprot.org)
  • BAX is a member of the Bcl-2 gene family. (wikipedia.org)
  • The BAX gene was the first identified pro-apoptotic member of the Bcl-2 protein family. (wikipedia.org)
  • To investigate the role of Bcl-xL in osteoclasts, we generated mice with osteoclast-specific conditional deletion of Bcl-x (referred to herein as Bcl-x cKO mice) by mating Bcl-xfl/fl mice with mice in which the gene encoding the Cre recombinase has been knocked into the cathepsin K locus and specifically expressed in mature osteoclasts. (elsevier.com)
  • Immunohistochemical analysis of normal human lymphoid tissues indicated that BCL-6 expression is topographically restricted to germinal centers including all centroblasts and centrocytes. (uniprot.org)
  • Detection of Bcl-2 family member Bcl-G in mouse tissues using new monoclonal antibodies. (nih.gov)
  • Expression of HGF, Bcl-2 and Bax in tumor tissues was investigated by immunohistochemical staining, and the apoptotic index was evaluated using the Terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL) method in all of the NPC cases. (biomedsearch.com)
  • One hundred and forty-six primary operable breast cancer patients were investigated in order to identify the population of CD44+ and Bcl-2+ cells in paraffin-embedded tissues by immunohistochemistry. (aacrjournals.org)
  • Samples were analyzed TEI-6720 by Western blot using antibodies against Bcl-xL (BD Biosciences) and GST (ViroGen Corp., Watertown, MA) with anti-actin (Sigma-Aldrich) mainly because a loading control. (ecologicalsgardens.com)
  • BCL-6 protein is expressed in germinal-center B cells. (uniprot.org)
  • Because DLCL derive from germinal-center B cells, deregulated BCL-6 expression may contribute to lymphomagenesis by preventing postgerminal center differentiation. (uniprot.org)
  • As they requested, we have presented coimmunoprecipitation data showing endogenous p53-p21 protein interaction in IMR-32 and H460 cells ( Fig. 1 ). (aacrjournals.org)
  • For instance, binding of HA-BAD to BCL-xL and concomitant disruption of BAX:BCL-xL interaction was found to partly reverse paclitaxel resistance in human ovarian cancer cells. (wikipedia.org)
  • The p53/Bcl-2 and p53/Bcl-XL interaction were then investigated by different groups. (ntu.edu.sg)
  • The DNS binding domain of p53 was believed to be the binding site in the p53/Bcl-XL interaction. (ntu.edu.sg)
  • 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)
  • Significantly, the M-type receptors also bind with many mammalian sPLA2 [31, recommending that these protein will be the endogenous ligands for these receptors, and perhaps for the assortment of binding protein initially discovered with venom sPLA2. (techxprtz.com)
  • however, this did not translate into detectable reductions in VDAC1 protein assessed using Western blot (Fig. 5and and and with the loading control blots of GST depicted below. (ecologicalsgardens.com)
  • GST-VDAC1 and -3 destined robustly to purified recombinant Bcl-xL (Fig. 6release. (ecologicalsgardens.com)
  • The Bcl-2 protein, at a final concentration of 2.50A?10A inverted question mark8 M, is mixed with a fluorescent peptide (Fluorescein-REIGAQLRRMADDLNAQY), at a final concentration of 1.00A?10A inverted question mark8 M in a buffer solution (Hepes 10 mM, NaCl 150 mM, Tween20 0.05%, pH 7.4), in the presence or in the absence of increasing concentrations of test compounds. (nih.gov)
  • A fifth protein-peptide complex composed of another anti-apoptotic protein, Bcl-w, in complex with the peptide from Bim was also studied. (inserm.fr)
  • We used an integrated approach involving peptide array, deuterium exchange mass spectrometry (DXMS), and functional studies aided by the power of sufficient constraints from direct coupling analysis (DCA) to determine the dominant docked conformation of the NAF-1-Bcl-2 complex. (sigmaaldrich.com)
  • Photocontrollable Peptide-Based Switches Target the Anti-Apoptotic Protein Bcl-X-L". ChemBioChem. (wikipedia.org)
  • The system of coat protein (COP)II vesicle fission through the endoplasmic reticulum (ER) remains unclear. (techxprtz.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)
  • The p53 protein is a transcription factor that, when activated as part of the cell's response to stress, regulates many downstream target genes, including BAX. (wikipedia.org)
  • View conserved domains detected in this protein sequence using CD-search. (nih.gov)
  • Note that the 'protein existence' evidence does not give information on the accuracy or correctness of the sequence(s) displayed. (uniprot.org)
  • Protein Feature View is not available: No corresponding UniProt sequence found. (rcsb.org)
  • Todt F, Cakir Z, Reichenbach F, Youle RJ, Edlich F (2013) The C-terminal helix of Bcl-x(L) mediates Bax retrotranslocation from the mitochondria. (springer.com)
  • Recent insights about the biochemical and biological functions of the Bcl-2 family and its role in neoplasia are the focus of this review. (sciencemag.org)
  • Allemann's work on hydrogen transfer catalysing enzymes including dihydrofolate reductase has led to deep new insights into the contributions from quantum mechanical tunnelling and protein dynamics to the enormous rate accelerations typical of Nature's catalysts. (wikipedia.org)
  • Our results provide insight into the molecular basis for the promiscuous nature of this molecular recognition process by members of the Bcl-2 protein family. (inserm.fr)