bcl-2-Associated X Protein
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
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.
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.
Hep G2 Cells
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.
Fragile X Mental Retardation Protein
Hepatitis B Virus, Woodchuck
Gene Expression Regulation, Viral
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.
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
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 22.214.171.124.
Tumor Suppressor Protein p53
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.
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
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
Amino Acid Sequence
Gene Expression Regulation
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)
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
Reverse Transcriptase Polymerase Chain Reaction
Hepatitis B Core Antigens
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.
Hepatocyte Nuclear Factor 1
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.
Gene Expression Regulation, Neoplastic
A gene silencing phenomenon whereby specific dsRNAs (RNA, DOUBLE-STRANDED) trigger the degradation of homologous mRNA (RNA, MESSENGER). The specific dsRNAs are processed into SMALL INTERFERING RNA (siRNA) which serves as a guide for cleavage of the homologous mRNA in the RNA-INDUCED SILENCING COMPLEX. DNA METHYLATION may also be triggered during this process.
A 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
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
Hepatocyte Nuclear Factor 1-alpha
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.
BH3 Interacting Domain Death Agonist Protein
Recombinant Fusion Proteins
Cyclic AMP Response Element-Binding Protein
Chromosomes, Human, Pair 18
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.
Real-Time Polymerase Chain Reaction
Cell Transformation, Neoplastic
Cell Line, Transformed
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 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.
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.
Sequence Homology, Amino Acid
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.
Simian virus 40
Disease Models, Animal
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).
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 enzymes
Proteins whose abnormal expression (gain or loss) are associated with the development, growth, or progression of NEOPLASMS. Some neoplasm proteins are tumor antigens (ANTIGENS, NEOPLASM), i.e. they induce an immune reaction to their tumor. Many neoplasm proteins have been characterized and are used as tumor markers (BIOMARKERS, TUMOR) when they are detectable in cells and body fluids as monitors for the presence or growth of tumors. Abnormal expression of ONCOGENE PROTEINS is involved in neoplastic transformation, whereas the loss of expression of TUMOR SUPPRESSOR PROTEINS is involved with the loss of growth control and progression of the neoplasm.
Malignant lymphoma in which the lymphomatous cells are clustered into identifiable nodules within the LYMPH NODES. The nodules resemble to some extent the GERMINAL CENTER of lymph node follicles and most likely represent neoplastic proliferation of lymph node-derived follicular center B-LYMPHOCYTES.
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
Retinoid X Receptors
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
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
Precursor Cells, B-Lymphoid
Immunoglobulin Heavy Chains
Bacteriophage phi X 174
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.
Precursor Cells, T-Lymphoid
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
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.
Tumor Suppressor Proteins
Proto-Oncogene Proteins c-myc
Gene Rearrangement, B-Lymphocyte
Oligonucleotide Array Sequence Analysis
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
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.
Factor X Deficiency
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
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
I-kappa B Kinase
Oncogene Proteins, Fusion
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
bcl-2 Homologous Antagonist-Killer Protein
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.
Polymorphism, Single Nucleotide
Genes whose gain-of-function alterations lead to NEOPLASTIC CELL TRANSFORMATION. They include, for example, genes for activators or stimulators of CELL PROLIFERATION such as growth factors, growth factor receptors, protein kinases, signal transducers, nuclear phosphoproteins, and transcription factors. A prefix of "v-" before oncogene symbols indicates oncogenes captured and transmitted by RETROVIRUSES; the prefix "c-" before the gene symbol of an oncogene indicates it is the cellular homolog (PROTO-ONCOGENES) of a v-oncogene.
A technique for identifying specific DNA sequences that are bound, in vivo, to proteins of interest. It involves formaldehyde fixation of CHROMATIN to crosslink the DNA-BINDING PROTEINS to the DNA. After shearing the DNA into small fragments, specific DNA-protein complexes are isolated by immunoprecipitation with protein-specific ANTIBODIES. Then, the DNA isolated from the complex can be identified by PCR amplification and sequencing.
Lymphocytes responsible for cell-mediated immunity. Two types have been identified - cytotoxic (T-LYMPHOCYTES, CYTOTOXIC) and helper T-lymphocytes (T-LYMPHOCYTES, HELPER-INDUCER). They are formed when lymphocytes circulate through the THYMUS GLAND and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen.
Motifs in DNA- and RNA-binding proteins whose amino acids are folded into a single structural unit around a zinc atom. In the classic zinc finger, one zinc atom is bound to two cysteines and two histidines. In between the cysteines and histidines are 12 residues which form a DNA binding fingertip. By variations in the composition of the sequences in the fingertip and the number and spacing of tandem repeats of the motif, zinc fingers can form a large number of different sequence specific binding sites.
Bcl-2 regulates amplification of caspase activation by cytochrome c. (1/2563)Caspases, a family of specific proteases, have central roles in apoptosis . 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  . 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    . 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  ) 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)
Acceleration of apoptotic cell death after the cleavage of Bcl-XL protein by caspase-3-like proteases
Interleukin-2 (IL-2)-dependent T cell clone CTLL-2 underwent apoptosis by deprivation of IL-2 from culture medium. The decrease in the anti-apoptotic Bcl-XL protein level was observed during apoptosis after IL-2 withdrawal. We found that Bcl-XL protein was cleaved to produce two 18 kDa fragments dur …
3jya - Proteopedia, life in 3D
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. ...
Heat-induced fibrillation of BclXL apoptotic repressor<...
TY - JOUR. T1 - Heat-induced fibrillation of BclXL apoptotic repressor. AU - Bhat, Vikas. AU - Olenick, Max B.. AU - Schuchardt, Brett J.. AU - Mikles, David C.. AU - Deegan, Brian J.. AU - McDonald, Caleb B.. AU - Seldeen, Kenneth L.. AU - Kurouski, Dmitry. AU - Faridi, Mohd Hafeez. AU - Shareef, Mohammed M.. AU - Gupta, Vineet. AU - Lednev, Igor K.. AU - Farooq, Amjad. PY - 2013/1/1. Y1 - 2013/1/1. N2 - The BclXL apoptotic repressor bears the propensity to associate into megadalton oligomers in solution, particularly under acidic pH. Herein, using various biophysical methods, we analyze the effect of temperature on the oligomerization of BclXL. Our data show that BclXL undergoes irreversible aggregation and assembles into highly-ordered rope-like homogeneous fibrils with length in the order of mm and a diameter in the μm-range under elevated temperatures. Remarkably, the formation of such fibrils correlates with the decay of a largely α-helical fold into a predominantly β-sheet architecture ...
摘要(Abstract)： 目的探讨孕期不同剂量苯并(a)芘暴露对仔鼠肝脏凋亡相关蛋白Bcl-xl和Bax表达水平的影响。方法将雌雄大鼠合笼后雌性SD大鼠见阴栓确定为受孕,以检出日为孕期第0 d。将孕鼠随机分为4组,每组8只,分为对照组(玉米油)和苯并(a)芘处理组(0.75 mg/kg、1.5 mg/kg和3 mg/kg)。从妊娠第3 d开始经灌胃苯并(a)芘直到妊娠第17 d结束,分别在孕0、4、7、14、19 d称孕鼠体重。待其自然分娩后24 h内测量仔鼠的体重、身长及尾长,然后取仔鼠肝脏,采用Western blot方法检测仔鼠肝脏中Bcl-xl和Bax蛋白的表达水平。结果随着孕期苯并(a)芘暴露水平的增加,新生仔鼠体重、身长、尾长等生长发育指标均有一定程度的下降,但未达到显著性差异(P>0.05)。Western blot结果显示,与对照组相比,中、高剂量染毒组仔鼠肝脏的Bcl-xl蛋白表达均明显下降,Bax蛋白表达均明显升高,差异均有统计学意义( ...
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 ...
3r85 - Proteopedia, life in 3D
The SOUL protein is known to induce apoptosis by provoking the mitochondrial permeability transition and a sequence homologous to the Bcl-2 homology 3 (BH3) domains has been recently identified in it thus making it a potential new member of the BH3-only protein family. Here we present NMR, SPR and crystallographic evidence that a peptide spanning SOUL residues 147 - 172 interacts with the anti-apoptotic protein Bcl-xL. We have crystallized SOUL alone and the complex of its BH3 domain peptide with Bcl-xL and solved their three-dimensional structures. The SOUL monomer is a single domain organized as a distorted beta barrel with eight anti-parallel strands and two alpha helices. The BH3 domain extends across 15 residues at the end of the second helix and 8 amino acids in the chain following it. There are important structural differences in the BH3 domain in the intact SOUL molecule and the same sequence bound to Bcl-xL. Structural changes in the BH3 domain of SOUL protein upon interaction with the ...
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 ...
Immunohistochemical analysis of bcl-2, bax, bcl-X, and mcl-1 expression in prostate cancers
Proteins encoded by bcl-2 family genes are important regulators of programmed cell death and apoptosis. Alterations in the expression of these apoptosis-regulating genes can contribute to the origins of cancer, as well as adversely influence tumor responses to chemo- and radiotherapy. Using antibodi …
A-371191 | CAS#406228-58-8 | Bcl-XL antagonist | MedKoo
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.
WEHI-539 | Chemical Probes
WEHI-539 is an inhibitor of BCL-2 family proteins, binding potently and selectively to BCL-XL with an IC50 of ~1.1 nM. It was the first small molecule that selectively antagonizes the prosurvival activity of BCL-XL with nM potency. The discovery of WEHI-539 provided a valuable tool for shedding light on BCL-XL and apoptosis & tumor growth.. The solubility of this compound in DMSO is ,10 mM; its molecular weight is 583.7, Log P = 6.86 (CLogP = 3.81), tPSA = 121.66. It is highly protein bound, likely has poor in vivo properties and has a labile and potentially toxic hydrazone moiety. It is currently one of three BCL-XL inhibitor probes being investigated (along with A-1155463 & A-1331852); In general, they all have similar physicochemical properties (but the two AbbVie compounds are devoid of the hydrazone moiety).. Platelets are known to depend on BCL-XL for their survival, and WEHI-539 induced apoptosis in both mouse (0-3 uM) and human platelets (log uM=0.01 to 100); this activity could be ...
Bcl-X | ALZFORUM
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.. ...
Bcl-xL Is Expressed in Neuroblastoma Cells and Modulates Chemotherapy-induced Apoptosis | Cancer Research
bcl-x is a new member of the bcl-2 gene family and is highly expressed in neural tissues. The present study was designed to determine the expression of the bcl-x gene products in neuroblastoma (NB) and their role in the modulation of chemotherapy-induced apoptosis. Twenty-seven NB cell lines were screened by quantitative immunoprecipitation for Bcl-xL, Bcl-xS, and Bcl-2 expression. None of the cell lines expressed Bcl-xS. Twenty-four of 27 (88%) of the NB cell lines expressed Bcl-xL and 21 of 27 (78%) were positive for Bcl-2. The level of Bcl-xL and Bcl-2 expression was variable among the lines analyzed. Bcl-2 expression was restricted to cells of chromaffin lineage, whereas Bcl-xL was seen in both chromaffin and nonchromaffin lines. To determine whether Bcl-xL could mediate chemotherapy resistance, a NB cell line expressing negligible levels of Bcl-xL was transfected with a bcl-xL expression vector, and unique clones were generated expressing variable levels of Bcl-xL. Cells were treated either ...
Rituximab-Induced Inhibition of YY1 and Bcl-xL Expression in Ramos Non-Hodgkins Lymphoma Cell Line via Inhibition of NF-κB...
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 ...
3VBV | EXPLOITATION OF HYDROGEN BONDING CONSTRAINTS AND FLAT HYDROPHOBIC ENERGY LANDSCAPES IN PIM-1 KINASE NEEDLE SCREENING AND...
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.
Marine Drugs | Free Full-Text | Fucoidan Extract Enhances the Anti-Cancer Activity of Chemotherapeutic Agents in MDA-MB-231...
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
Bcl-XL displays restricted distribution during T cell development and inhibits multiple forms of apoptosis but not clonal...
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 ...
Bcl-XL and Bcl-2 repress a common pathway of cell death. | JEM
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 ...
Anti BAD (pSer112) Antibody | Bio-Rad
|strong|Rabbit anti BAD (pSer112) antibody|/strong| recognizes Bcl2-associated agonist of cell death (BAD), also known as Bcl-xL/Bcl-2-associated death promoter, Bcl-2 binding component 6 or Bcl2-L-8,…
February | 2013 | AKT inhibitor|AKT pathway
Inside a latest examine we mentioned that over-expression of BCL-2 or BCL-XL failed to safeguard leukemia cells from co-treatment with the BCL-2/BCLXL inhibitor ABT-737 as well as the CDK inhibitor roscovitine,probably reflecting a vital contribution of MCL-1 down-regulation to your … Continue reading →. ...
Search Results | Anesthesiology | American Society of Anesthesiologists
Background The possibility of altering outcome from ischemia-like injury by overexpressing the anti-cell death gene bcl-xL was studied. Cells are known to die by different pathways including apoptosis, or programmed cell death, and necrosis. The bcl-xL gene is a member of a family of apoptosis regulating genes and often displays the death-inhibiting properties of the prototype of this family, bcl-2. It is of special interest to study bcl-xL for possible brain protection, because, unlike bcl-2, it is important for normal brain development. Methods Overexpression of bcl-xL was achieved in primary astrocyte cultures using a retroviral vector. Cultures of astrocytes overexpressing bcl-xL or a control gene were injured by hydrogen peroxide, glucose deprivation, or combined oxygen and glucose deprivation. Outcome was assessed morphologically and by release of lactate dehydrogenase. We assessed antioxidant effects by measuring glutathione using monochlorobimane, ferritin by immunoblotting, the level of ...
Data Availability StatementAll datasets presented in this study are included in the article/supplementary material - Discovery...
Data Availability StatementAll datasets presented in this study are included in the article/supplementary material. sensitized NSCLC cells to celecoxib-induced apoptosis by activating caspase-9, -8, -3, and -7, upregulating the pro-apoptotic proteins Bad and Bax, and downregulating the antiapoptotic proteins Bcl-xl and Bcl-2. Moreover, the superior anticancer effect of combined therapy was also due to suppression of Raf-MEK-ERK cascades and PI3K-AKT signaling, which is conducive to overcoming drug resistance. In addition, either celecoxib alone or Y-33075 dihydrochloride in combination with metformin suppressed NSCLC cell migration and invasion by inhibiting FAK, N-cadherin, and matrix metalloproteinase-9 activities. Together, our study provided a rational combination strategy with a low dosage of celecoxib and metformin for preclinical cancer application. experiments showed that combination therapy inhibits tumor growth in A549 xenograft-bearing nude mice more effectively than metformin and ...
Developing and Activated T Cell Survival Depends on Differential Signaling Pathways to Regulate Anti-Apoptotic Bcl-xL
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.
Protein Prevents Tissue Injury But Encourages Tumor Growth | EmaxHealth
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 ...
Practical Fragments: Second fragment-based drug approved
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 | A1331852 | 1430844-80-6 | MedKoo
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.
Cisplatin and TNF-α downregulate transcription of Bcl-xL in murine malignant mesothelioma cells<...
TY - JOUR. T1 - Cisplatin and TNF-α downregulate transcription of Bcl-xL in murine malignant mesothelioma cells. AU - Fox, S.A.. AU - Kusmiaty, D.. AU - Loh, S.. AU - Dharmarajan, Arunasalam. AU - Garlepp, M.J.. PY - 2005. Y1 - 2005. N2 - Malignant mesothelioma (MM) is an aggressive and highly chemo-resistant tumour. In this study, we examined cisplatin-induced apoptosis in mouse models of this disease and investigated the role of constitutive and inducible expression of apoptosis related genes in this process. All of the four mouse MM cell lines examined expressed Bax, Bcl-xL, c-Myc, and caspase-3 but not Bcl-2. Cisplatin-induced apoptosis characterised by DNA fragmentation and cell death while caspase-3/7 was activated in 3 of 4 cell lines. Quantitation of basal gene expression showed significant differences but there was no correlation between single genes and cisplatin sensitivity. In the AC29 and AB1 models, both cisplatin and TNF-alpha downregulated Bcl-xL gene expression, indicating that ...
Role of BAX in the Apoptotic Response to Anticancer Agents | Science
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 ...
Expression of Bcl-2 and its homologues in human eosinophils - Modulation by interleukin-5<...
TY - JOUR. T1 - Expression of Bcl-2 and its homologues in human eosinophils - Modulation by interleukin-5. AU - Dewson, G AU - Walsh, Garry. AU - Wardlaw, A J PY - 1999/4. Y1 - 1999/4. N2 - The Bcl-2 family has been shown to be vital regulators of programmed cell death in numerous systems. To investigate the role of such proteins in the regulation of apoptosis of eosinophils, the expression of Bcl-2 and homologues Bcl-x(L), (death antagonists), Bax, and Bcl-x(S) (death agonists) were examined by immunoblot, flow cytometry, and reverse transcriptase-polymerase chain reaction analysis, Potential modulation of apoptosis-associated molecules during spontaneous apoptosis and in the presence of interleukin (IL)-5 was also investigated. Peripheral blood eosinophils were found to express constitutively Pax and Bcl-x, but Bcl-2 was absent. Analysis of mRNA revealed that the bcl-x(L), isoform predominated, although bcl-x(S), was also detectable. Spontaneous apoptosis due to culturing in the absence of ...
Because of the complex nature of wound healing process, an injury on the skin can pose several challenges and are likely pose complications especially when they are acute. They can as well deteriorate from acute to chronic conditions which will require external intervention best understood by a specialist physician to get the area affected by. ...
Pesquisa | Portal Regional da BVS
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 ...
Bcl-2 Antibody - AF6139 - affinity biosciences
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 pSer136/99 - AP02799PU-N | acris-antibodies.com
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.
BCL2L1/Bcl-2-like protein 1/B-cell Lymphoma-extra Large/Bcl-xL | Ubigene
TEL :. +86 153 6067 3248 (Intl). US Toll free: 855 777 3210 EU Toll free: 800 3272 9252 Korea Toll free: 001 800 3272 9252 (Telecom ...
Global Smoked mackerel Market Professional Survey Report 2017 : ReportsnReports
[104 Pages Report] Check for Discount on Global Smoked mackerel Market Professional Survey Report 2017 report by QYResearch Group. This report studies Smoked mackerel in Global market, especially in...
Bcl-2, Bcl-x |inf|L|/inf|, and Bcl-w are not equivalent targets of ABT-737 and navitoclax (ABT-263) in lymphoid and leukemic...
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 ...
Pro-Survival Bcl-2 Family Antibody Sampler Kit II | Cell Signaling Technology
The Bcl-2 family consists of a number of evolutionarily conserved proteins containing Bcl-2 homology domains (BH) that regulate apoptosis through control of mitochondrial membrane permeability and release of cytochrome c (1-3). Four BH domains have been identified (BH1-4) that mediate protein interactions. The family can be separated into three groups based upon function and sequence homology: pro-survival members include Bcl-2, Bcl-xL, Mcl-1, A1 and Bcl-w; pro-apoptotic proteins include Bax, Bak and Bok; and BH3 only proteins Bad, Bik, Bid, Puma, Bim, Bmf, Noxa and Hrk. Interactions between death-promoting and death-suppressing Bcl-2 family members has led to a rheostat model in which the ratio of pro-apoptotic and anti-apoptotic proteins controls cell fate (4). Thus, pro-survival members exert their behavior by binding to and antagonizing death-promoting members. In general, the BH3-only members can bind to and antagonize the pro-survival proteins leading to increased apoptosis (5). While ...
Proteins arginine methylation is a common posttranslational adjustment catalyzed by way | CDK-II inhibitor KN-62 increase T...
Proteins arginine methylation is a common posttranslational adjustment catalyzed by way of a category of the proteins arginine methyltransferases (PRMTs). with 14-3-3 protein, which occurs after Akt-mediated Veliparib phosphorylation, is certainly negatively governed by PRMT1. Furthermore, PRMT1 knockdown prevents mitochondrial localization of Poor and its own binding towards the antiapoptotic BCL-XL proteins. Poor overexpression causes a rise in apoptosis with concomitant activation of caspase-3, whereas PRMT1 knockdown considerably suppresses these apoptotic procedures. Taken jointly, our results put in a brand-new dimension towards the intricacy of posttranslational Poor regulation and offer proof that arginine methylation in a Akt consensus phosphorylation theme features as an inhibitory adjustment against Akt-dependent success signaling. A complicated interplay between pro- and antiapoptotic people from the B-cell lymphoma 2 (BCL-2) category of proteins regulates apoptosis by regulating ...
The N-terminal helix of Bcl-xL targets mitochondria<...
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 - ...
Massive cell death of immature hematopoietic cells and neurons in Bcl-x-deficient mice | Science
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. ...
Neue Ansätze zur zielgerichteten Behandlung solider Tumoren
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 ...
Neue Ansätze zur zielgerichteten Behandlung solider Tumoren
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 ...
Molecular Basis of the Interaction Between the Antiapoptotic Bcl-2 Family Proteins and the Proapoptotic Protein ASPP2
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TNF related apoptosis inducing ligand; totice bcl-2, bcl-x, bcl-w, mcl-1 şi A1 eli- colică normală. Pattern-ul de expresie ...
Venetoclax (ABT-199) | Bcl-2 抑制剂 | 现货供应 | 美国品牌 | 免费采购电话400-668-6834
Venetoclax (ABT-199, GDC-0199)是一种Bcl-2选择性抑制剂，无细胞试验中Ki为
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Apoptosis Regulator BAX (Bcl 2 Like Protein 4 or BCL2L4 or BAX) Pipeline Insight and Therapeutic Assessment Reviewed in 2017 -...
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 ...
Bim and Bad mediate imatinib-induced killing of Bcr/Abl+ leukemic cells, and resistance due to their loss is overcome by a BH3...
Imatinib has shown remarkable clinical benefit for treatment of Bcr/Abl+ leukemia, especially CML patients in early chronic phase. However, it has become clear that rare clones with mutations that confer resistance to imatinib (e.g., mutations in bcr-abl that prevent imatinib binding) can survive, and this resistance can lead to relapse and limits the effects for patients with advanced disease (1). Because the inhibition of cell proliferation by the blockade of Bcr/Abl with imatinib is not sufficient for eradicating Bcr/Abl+ leukemic clones, a better understanding of the mechanisms by which imatinib kills cells and how this killing can be augmented may lead to improved therapeutic strategies.. Although, our study confirmed that Bcl-2 or Bcl-xL overexpression (7) or RNAi-mediated reduction of Bim (8, 9) inhibits imatinib-induced apoptosis in K562 cells, we found that it is the combination of Bim and Bad that accounts for the killing activity of imatinib. Imatinib caused a marked reduction in ...
Search bcl 2 - SlidePt.Net
All Advanced Stage Non-Hodgkins Lymphomas With a Polymerase Chain Reaction Amplifiable Breakpoint of bcl-2 Have Residual Cells Containing the bcl-2 Rearrangement at Evaluation and After Treatment Cyclin E but not bcl-2, bax or mcl-1 is differentially expressed in ZAP 70-positive and ZAP 70-negative B-CLL cells In Vitro and In Vivo Transfer of bcl-2 Gene into Keratinocytes Suppresses UVB-induced Apoptosis Corticosterone differentially regulates bax, bcl-2 and bcl-x mRNA levels in the rat hippocampus Apoptosis and expression of bcl-2 ?, ? mRNA isoforms and protein in neuroblastoma Down-Regulation of bcl-2 by p53 in Breast Cancer Cells Role of bcl-2 in Growth Factor Triggered Signal Transduction1 Low bcl-2 expression and increased spontaneous apoptosis in T-lymphocytes from newly-diagnosed IDDM patients Essential Role of the Prosurvival bcl-2 Homologue A1 in Mast Cell Survival After Allergic Activation bcl-2 and bak may play a pivotal role in sodium butyrate-induced apoptosis in colonic epithelial cells;
Tissue expression of BCL2L1 - Staining in lymph node - The Human Protein Atlas
Expression of BCL2L1 (Bcl-X, bcl-xL, bcl-xS, BCL2L, BCLX, PPP1R52) in lymph node tissue. Antibody staining with HPA035734 in immunohistochemistry.
Publications - www.cemm.at
Strobl J, Pandey RV, Krausgruber T, Kleissl L, Reininger B, Herac M, Bayer N, Krall C, Wohlfarth P, Mitterbauer M, Kalhs P, Rabitsch W, Bock C, Hopfinger G, Stary G. Anti-Apoptotic Molecule BCL2 Is a Therapeutic Target in Steroid- Refractory Graft-Versus-Host Disease. J Invest Dermatol. 2020 Apr 2:S0022-202X(20)31252-5. doi: 10.1016/j.jid.2020.02.029. Epub ahead of print ...
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premixing protein shakes is bad??! - AnabolicMinds.com
i did a search about premixing protein shakes and leaving them in the fridge and consuming them later....and people say not to do it as the protein
BCL-2 Cancer. ALN-VSP02. Solid tumor. VEGF, kinesin spindle protein Cancer. NCT00672542. Metastatic melanoma. LMP2, LMP7, and ... RNA has been largely investigated within its role as an intermediary in the translation of genes into proteins. More active ... Such 3'-UTRs often contain both binding sites for microRNAs (miRNAs) as well as for regulatory proteins. By binding to specific ... When this happens, the RNAi machinery goes into action, debilitating the mRNAs of the proteins that would be required to move ...
Marginal zone B-cell lymphoma
The lymphocytes have marker protein profiles (e.g. CD20 and Bcl-2 positive; CD5, cyclin D1 and CD10 negative) that are typical ... CD20 and BCL-6 but not CD10 proteins. Patients with primary thyroid EMZL are at an increased risk of developing a more ... marker proteins but do not express the cyclin D1 marker protein., the T-cell marker, CD10, or BCL6. There are various EMZL ... whose protein product indirectly regulates activation of the NF-κB cell signaling pathway; 4) KLF2 whose product protein is a ...
Sexually dimorphic nucleus
Such proteins include Bcl-2 and Bax. Bcl-2 is an antiapoptotic protein. The level of Bcl-2 in PD8 male rats is much higher than ... Tsukahara S, Kakeyama M, Toyofuku Y (2006). "Sex Differences in the level of Bcl-2 Family Proteins and Caspase-3 Activation in ... It is proved that Bcl-2 level in AVPV is higher whereas Bax level is lower in females than in males, just as being opposite of ... On the other hand, Bax, a proapoptotic protein, shows lower level in PD8 males than in PD8 females. Also, the number of active ...
5-MTHF: 5-methyltetrahydrofolate; 5,10-methyltetrahydrofolate; BAX: Bcl-2-associated X protein; BHMT: betaine-homocysteine S- ...
"Presenilin 1 protein directly interacts with Bcl-2". J. Biol. Chem. 274 (43): 30764-9. doi:10.1074/jbc.274.43.30764. PMID ... Levesque G (1999). "Presenilins interact with armadillo proteins including neural-specific plakophilin-related protein and beta ... They found that there is higher level expression of both proteins and a multidrug resistance-associated protein 1 (ABCC1) was ... "A new splice variant of glial fibrillary acidic protein, GFAP epsilon, interacts with the presenilin proteins". J. Biol. Chem. ...
Wang HG, Takayama S, Rapp UR, Reed JC (July 1996). "Bcl-2 interacting protein, BAG-1, binds to and activates the kinase Raf-1 ... Reed JC, Zha H, Aime-Sempe C, Takayama S, Wang HG (1997). "Structure-function analysis of Bcl-2 family proteins. Regulators of ... Wang HG, Rapp UR, Reed JC (November 1996). "Bcl-2 targets the protein kinase Raf-1 to mitochondria". Cell. 87 (4): 629-38. doi: ... 14-3-3 proteins also contribute to the autoinhibition. As 14-3-3 proteins are all known to form constitutive dimers, their ...
... attaches to a protein called Bcl-2. This protein is present in high amounts in CLL cancer cells, where it helps the ... Venetoclax blocks the anti-apoptotic B-cell lymphoma-2 (Bcl-2) protein, leading to programmed cell death of CLL cells. ... By attaching to Bcl-2 and blocking its actions, venetoclax causes the death of cancer cells and thereby slows down progression ... Overexpression of Bcl-2 in some lymphoid malignancies has sometimes shown to be linked with increased resistance to ...
... resides on the outer mitochondrial membrane where it co-localizes with the apoptotic Bcl-2 family protein BID. MTCH2 ... Gross A (August 2016). "BCL-2 family proteins as regulators of mitochondria metabolism". Biochimica et Biophysica Acta (BBA) - ... Mitochondrial carrier homolog 2 also known as MTCH2 is a protein which in humans is encoded by the MTCH2 gene. ... Gross A (June 2005). "Mitochondrial carrier homolog 2: a clue to cracking the BCL-2 family riddle?". Journal of Bioenergetics ...
"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 ...
Bcl-2-like protein 12 is a protein that in humans is encoded by the BCL2L12 gene. The protein encoded by this gene belongs to ... This protein contains a Bcl-2 homology domain 2 (BH2). The function of this gene has not yet been determined. Two alternatively ... 2001). "In vitro selection and characterization of Bcl-X(L)-binding proteins from a mix of tissue-specific mRNA display ... the Bcl-2 protein family. Bcl-2 family members form hetero- or homodimers and act as anti- or pro-apoptotic regulators that are ...
2004). "FAST is a BCL-X(L)-associated mitochondrial protein". Biochem. Biophys. Res. Commun. 318 (1): 95-102. doi:10.1016/j. ... The protein encoded by this gene is a member of the serine/threonine protein kinase family. This kinase was shown to be ... 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173-8. doi:10.1038 ... "FAST is a survival protein that senses mitochondrial stress and modulates TIA-1-regulated changes in protein expression". Mol ...
... is an inhibitor of the Bcl-2 family of proteins. This inhibition induces apoptosis in cancer cells, preventing tumor ... a Small-Molecule BCL-2 Family Antagonist, for Patients with Myelofibrosis". Clinical Lymphoma, Myeloma & Leukemia. 10 (4): 285- ... a small molecule pan-Bcl-2 family antagonist in patients with relapsed or refractory classical Hodgkin lymphoma". Blood. 119 (9 ... "Mechanisms of Antileukemic Activity of the Novel Bcl-2 Homology Domain-3 Mimetic GX15-070 (Obatoclax)". Cancer Research. 68 (9 ...
Examples of viral Bcl-2 proteins include the Epstein-Barr virus BHRF1 protein and the adenovirus E1B 19K protein. Some viruses ... The adenovirus E1B-55K protein and the hepatitis B virus HBx protein are examples of viral proteins that can perform such a ... Bcl-Xl and Bcl-2) members of the Bcl-2 family are established. This balance is the proportion of proapoptotic homodimers that ... these inhibitory proteins target retinoblastoma tumor-suppressing proteins. These tumor-suppressing proteins regulate the cell ...
October 1994). "Adenovirus E1B 19 kDa and Bcl-2 proteins interact with a common set of cellular proteins". Cell. 79 (2): 341-51 ... December 1997). "The E1B 19K/Bcl-2-binding protein Nip3 is a dimeric mitochondrial protein that activates apoptosis". The ... December 1997). "The E1B 19K/Bcl-2-binding protein Nip3 is a dimeric mitochondrial protein that activates apoptosis". The ... BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 is a protein that in humans is encoded by the BNIP3 gene. BNIP3 is a ...
Members of the Bcl-2 family of pro-apoptotic proteins can induce the opening of the VDAC (12). This will cause the same release ... Scientists have found that binding depressors to Bcl-2 anti-apoptotic proteins inhibits them and leaves direct activators free ... The term Apoptosome was first introduced in Yoshihide Tsujimoto's 1998 paper "Role of Bcl-2 family proteins in apoptosis: ... Tsujimoto Y (November 1998). "Role of Bcl-2 family proteins in apoptosis: apoptosomes or mitochondria?". Genes to Cells. 3 (11 ...
Fernandez-Sarabia MJ, Bischoff JR (November 1993). "Bcl-2 associates with the ras-related protein R-ras p23". Nature. 366 (6452 ... Ras-related protein R-Ras is a protein that in humans is encoded by the RRAS gene. RRAS has been shown to interact with: ARAF, ... Fernandez-Sarabia MJ, Bischoff JR (1993). "Bcl-2 associates with the ras-related protein R-ras p23". Nature. 366 (6452): 274-5 ... "Novel raf kinase protein-protein interactions found by an exhaustive yeast two-hybrid analysis". Genomics. 81 (2): 112-25. doi: ...
... encodes a protein that activates apoptosis and interacts selectively with survival-promoting proteins Bcl-2 and Bcl-X(L)". EMBO ... Activator of apoptosis Hrk regulates apoptosis through interaction with death-repressor proteins Bcl-2 and Bcl-X(L). The HRK ... Whitfield J, Harada K, Bardelle C, Staddon JM (2004). "High-throughput methods to detect dimerization of Bcl-2 family proteins ... "High-throughput methods to detect dimerization of Bcl-2 family proteins". Anal. Biochem. 322 (2): 170-8. doi:10.1016/j.ab. ...
Mitochondrial outer membrane permeabilization
Initiation of MOMP involves Bcl-2 family proteins, including BAX and BAK. The outer mitochondrial membrane, typically permeable ... Once triggered, it results in the diffusion of proteins from the space between the inner and outer mitochondrial membranes into ... Kalkavan, Halime; Green, Douglas R. (2018). "MOMP, cell suicide as a BCL-2 family business". Cell Death & Differentiation. 25 ( ... to molecules smaller than 5 kDa, forms pores during MOMP that allow it to accommodate proteins larger than 100 kDa. During MOMP ...
"Adenovirus E1B 19 kDa and Bcl-2 proteins interact with a common set of cellular proteins". Cell. 79 (2): 341-51. doi:10.1016/ ... BCL2/adenovirus E1B 19 kDa protein-interacting protein 2 is a protein that in humans is encoded by the BNIP2 gene. This gene is ... Low BC, Lim YP, Lim J, Wong ES, Guy GR (November 1999). "Tyrosine phosphorylation of the Bcl-2-associated protein BNIP-2 by ... 2002). "Estrogen neuroprotection: the involvement of the Bcl-2 binding protein BNIP2". Brain Res. Brain Res. Rev. 37 (1-3): 335 ...
Hypothermia therapy for neonatal encephalopathy
2001). "Mild hypothermia increases Bcl-2 protein expression following global cerebral ischemia". Brain Res. 95 (1-2): 75-85. ... 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. ...
"Proapoptotic Bak is sequestered by Mcl-1 and Bcl-xL, but not Bcl-2, until displaced by BH3-only proteins". Genes Dev. 19 (11): ... 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. ...
"The RNA-binding protein Sam68 modulates the alternative splicing of Bcl-x". J Cell Biol. 176 (7): 929-39. doi:10.1083/jcb. ... "Induced direct binding of the adapter protein Nck to the GTPase-activating protein-associated protein p62 by epidermal growth ... "Guanosine triphosphatase-activating protein-associated protein, but not src-associated protein p68 in mitosis, is a part of ... KH domain-containing, RNA-binding, signal transduction-associated protein 1 is a protein that in humans is encoded by the ...
"Metabolic regulation of protein N-alpha-acetylation by Bcl-xL promotes cell survival". Cell. 146 (4): 607-20. doi:10.1016/j. ... acetylation of ribosomal protein S18". Protein Science. 17 (10): 1781-90. doi:10.1110/ps.035899.108. PMC 2548364. PMID 18596200 ... "N-α-acetyltransferase 10 protein suppresses cancer cell metastasis by binding PIX proteins and inhibiting Cdc42/Rac1 activity ... "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173-8. Bibcode:2005Natur. ...
Mitochondrial apoptosis-induced channel
Members of the Bcl-2 protein family regulate apoptosis by controlling the formation of MAC: the pro-apoptotic members Bax and/ ... by BCL-2 family proteins". Biochim Biophys Acta. 1762 (2): 191-201. doi:10.1016/j.bbadis.2005.07.002. PMID 16055309. Evgeny V. ... or Bak form MAC, whereas the anti-apoptotic members like Bcl-2 or Bcl-xL prevent MAC formation. Once formed, MAC mediates the ...
Inhibitors of different members of the bcl-2 family of anti-apototic proteins. Studies of cell cultures of senescent human ... FOXO4 can bind with p53 protein to induce cellular senescence. A peptide competing with FOXO4 can act as a senolytic by ... endothelial cells have shown that both fisetin and quercetin induce apoptosis by inhibition of the anti-apoptotic protein Bcl- ... "Activity of the Bcl-2 Family Inhibitor ABT-263 in a Panel of Small Cell Lung Cancer Xenograft Models". Clinical Cancer Research ...
... it encodes both of the human proteins Bcl-xL and Bcl-xS. The protein encoded by this gene belongs to the BCL-2 protein family. ... encodes a protein that activates apoptosis and interacts selectively with survival-promoting proteins Bcl-2 and Bcl-X(L)". The ... "Identification of the protein-protein contact site and interaction mode of human VDAC1 with Bcl-2 family proteins". Biochemical ... Tagami S, Eguchi Y, Kinoshita M, Takeda M, Tsujimoto Y (Nov 2000). "A novel protein, RTN-XS, interacts with both Bcl-XL and Bcl ...
Watanabe N, Iwamura T, Shinoda T, Fujita T (June 1997). "Regulation of NFKB1 proteins by the candidate oncoprotein BCL-3: ... 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 ...
Bcl-2-like protein 10 is a protein that in humans is encoded by the BCL2L10 gene. The protein encoded by this gene belongs to ... This protein can interact with other members of BCL-2 protein family including BCL2, BCL2L1/BCL-X(L), and BAX. Overexpression ... the BCL-2 protein family. BCL-2 family members form hetero- or homodimers and act as anti- or pro-apoptotic regulators that are ... Ke N, Godzik A, Reed JC (2001). "Bcl-B, a novel Bcl-2 family member that differentially binds and regulates Bax and Bak". J. ...
Bcl-2-like protein 11, commonly called BIM, is a protein that in humans is encoded by the BCL2L11 gene. The protein encoded by ... It has been shown to interact with other members of the BCL-2 protein family, including BCL2, BCL2L1/BCL-X(L), and MCL1, and to ... 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 contains a Bcl-2 homology domain 3 (BH3). ...
Rudolf K. Allemann
"Photocontrollable Peptide-Based Switches Target the Anti-Apoptotic Protein Bcl-X-L". ChemBioChem. 9 (18): 3046-3054. doi: ... PMID 22068697.CS1 maint: multiple names: authors list (link) Luk, YPL Loveridge, EJ Allemann, RK (2015). "Protein motions and ... dihydrofolate reductase has led to deep new insights into the contributions from quantum mechanical tunnelling and protein ...
Homeobox protein Hox-D8 is a protein that in humans is encoded by the HOXD8 gene. ... 1989). "Complementary homeo protein gradients in developing limb buds". Genes Dev. 3 (5): 641-50. doi:10.1101/gad.3.5.641. PMID ... HOXD8+protein,+human at the US National Library of Medicine Medical Subject Headings (MeSH) ... "The thyroid transcription factor-1 gene is a candidate target for regulation by Hox proteins". EMBO J. 13 (14): 3339-47. PMC ...
FOXP2 - 维基百科，自由的百科全书
ATBF1 · BCL（6、11A、11B） · CTCF · E4F1 · EGR（1、2、3、4） · ERV3 · GFI1 · GLI-Krüppel family（1、2、3、REST、S2、YY1） · HIC（1、2） · HIVEP（1、 ... Rb · RBL1（英语：Retinoblastoma-like protein 1） · RBL2（英语：Retinoblastoma-like protein 2） ... protein homodimerization activity. · sequence-specific DNA binding. · metal ion binding. · protein heterodimerization activity ... FOXP2（Forkhead box protein P2 (FOXP2)）基因，即叉头框P2基因，是一个与言语功能的发育有关的基因。在人
p21, wolna encyklopedia
Towards a proteome-scale map of the human protein-protein interaction network. „Nature". 437 (7062), s. 1173-8, 2005. DOI: ... Novel dipeptidyl proteasome inhibitors overcome Bcl-2 protective function and selectively accumulate the cyclin-dependent ... a b Ono T, Kitaura H, Ugai H, Murata T, Yokoyama KK, Iguchi-Ariga SM, Ariga H. TOK-1, a novel p21Cip1-binding protein that ... Regulation of cyclin A-Cdk2 by SCF component Skp1 and F-box protein Skp2. „Mol. Cell. Biol.". 19 (1), s. 635-45, 1999. PMID: ...
ATBF1 • BCL (6, 11A, 11B) • CTCF • E4F1 • EGR (2, 3) • ERV3 • GFI1 • GLI-Kruppel familija (1, 2, 3, REST, S2, YY1) • HIC (1, 2) ... Bernstein PL, Herrick DJ, Prokipcak RD, Ross J (1992). "Control of c-myc mRNA half-life in vitro by a protein capable of ... Blackwood EM, Eisenman RN (1991). "Max: a helix-loop-helix zipper protein that forms a sequence-specific DNA-binding complex ... 1988). "A non-AUG translational initiation in c-myc exon 1 generates an N-terminally distinct protein whose synthesis is ...
Platelet-derived growth factor
Binding proteins: IGFBP (1, 2, 3, 4, 5, 6, 7). *Cleavage products/derivatives with unknown target: Glypromate (GPE, (1-3)IGF-1) ... a b Proto-Oncogene+Proteins+c-sis at the US National Library of Medicine Medical Subject Headings (MeSH) ... Hannink M, Donoghue DJ (1989). "Structure and function of platelet-derived growth factor (PDGF) and related proteins". Biochim ... The first engineered dominant negative protein was designed to inhibit PDGF  ...
Tumor necrosis factor alpha
For instance, NF-κB enhances the transcription of C-FLIP, Bcl-2, and cIAP1 / cIAP2, inhibitory proteins that interfere with ... protein binding. • protease binding. • tumor necrosis factor receptor binding. • cytokine activity. • identical protein binding ... positive regulation of protein complex assembly. • protein kinase B signaling. • positive regulation of cytokine production. • ... protein localization to plasma membrane. • positive regulation of protein catabolic process. • regulation of receptor activity ...
Minimal residual disease
Uses: M-protein level in the blood is standard of care and is used for almost all patients with multiple myeloma. Patient- ... Jun 2006). "The bcl-2/IgH rearrangement in a population of 204 healthy individuals: occurrence, age and gender distribution, ... Targets: M-protein levels in blood, patient-specific assays for immunoglobulin and T cell receptor genes (high levels of ... These proteins can be stained with fluorescent dye labeled antibodies and detected using flow cytometry. The limit of detection ...
Strok bahasa Indonesia, ensiklopedia bebas
Wiskott-Aldrich syndrome protein verprolin homologous-1 (WAVE-1) dan Bcl-xL akan membentuk kompleks protein mitokondrial untuk ... Myelin basic protein (MBP)[sunting , sunting sumber]. Bagian ini tidak memiliki referensi atau sumber tepercaya sehingga isinya ... Protein khas CNS seperti pancortin-2 akan berinteraksi dengan protein modulator aktin, ... Protein tau (TP)[sunting , sunting sumber]. Bagian ini tidak memiliki referensi atau sumber tepercaya sehingga isinya tidak ...
سرطان پروستات - ویکیپدیا، دانشنامهٔ آزاد
The protein ZIP1 is responsible for the active transport of zinc into prostate cells. One of the zinc's important roles is to ... The upregulation of BCL-2 after androgen ablation in prostate carcinoma cell lines and in a castrated-male rat model further ... Prostate specific membrane antigen is a transmembrane carboxypeptidase and exhibits folate hydrolase activity. This protein ... The absence of zinc is thought to occur via a silencing of the gene that produces the transporter protein ZIP1. ZIP1 is now ...
Bcl-2), MAP (mitogen-activated protein kinase) kinase pathway and the phosphorylation of Lck (lymphocyte-activated protein ... Bcl-2), MAP (mitogen-activated protein kinase) kinase pathway and the phosphorylation of Lck (lymphocyte-activated protein ... tyrosine phosphorylation of STAT protein. • positive regulation of tyrosine phosphorylation of STAT protein. • regulation of ... In humans with celiac disease IL-15 similarly suppresses apoptosis in T-lymphocytes by inducing Bcl-2 and/or Bcl-xL. ...
BAK1/Bcl-2 homologous antagonist killer. Bcl-2-associated death promoter. Anti-apoptotic:. Bcl-2. Bcl-xL. ... protein binding. • heme binding. • electron carrier activity. Cellular component. • cytosol. • protein phosphatase type 2A ... Soltys BJ, Gupta RS (2000). "Mitochondrial proteins at unexpected cellular locations: export of proteins from mitochondria from ... "Effect of constitutive 70-kDa heat shock protein polymerization on its interaction with protein substrate". The Journal of ...
protein binding. • cyclin-dependent protein serine/threonine kinase inhibitor activity. • ubiquitin protein ligase binding. • ... role of bcl-2, and the cyclin dependent kinase inhibitors P27 and P21". Leuk. Lymphoma. 43 (1): 51-7. doi:10.1080/ ... cyclin-dependent protein serine/threonine kinase activity. • protein kinase inhibitor activity. • protein kinase binding. • ... This article is about the p21Cip1 protein. For the p21/ras protein, see Ras (protein). For other uses, see P21 (disambiguation) ...
Hepatocyte nuclear factor 3-gamma (HNF-3G), also known as forkhead box protein A3 (FOXA3) or transcription factor 3G (TCF-3G) ... protein domain specific binding. • RNA polymerase II transcription factor activity, sequence-specific DNA binding. ... HNF-3G is a member of the forkheadclass of DNA-binding proteins. These hepatocyte nuclear factors are transcriptional ... Dintilhac A, Bernués J (2002). "HMGB1 interacts with many apparently unrelated proteins by recognizing short amino acid ...
Factor de necrose tumoral alfa, a enciclopedia libre
Por exemplo, o NF-κB potencia a transcrición de C-FLIP, Bcl-2, e cIAP1 / cIAP2, proteínas inhibidoras que interfiren coa ... "A novel form of TNF/cachectin is a cell surface cytotoxic transmembrane protein: ramifications for the complex physiology of ... que induce a expresión de Mn-SOD e Bcl-2. ... "Dynamic dissociating homo-oligomers and the control of protein ...
Programmed cell death
Manipulation of apoptosis regulator proteins Bcl-2 and Bax (overexpression of Bcl-2 or deletion of Bax) produces an increase in ... It has also been shown that in mice null for the proapoptotic factor Bax (Bcl-2-associated X protein) a larger percentage of ... and the scaffold protein FIP200. Class III PI3K complex, containing hVps34, Beclin-1, p150 and Atg14-like protein or ... Additionally, Bcl-2 inhibits Beclin-1-dependent autophagy, thereby functioning both as a pro-survival and as an anti-autophagic ...
... protein that promote osteoclast formation. Oxidative stress results when ethanol induces NOX expression, resulting in ROS ... "Spatial distribution of Bax and Bcl-2 in osteocytes after bone fatigue: complementary roles in bone remodeling regulation?". ...
Rob M Ewing, Chu Peter, Elisma Fred, Li Hongyan, Taylor Paul, et al., Large-scale mapping of human protein-protein interactions ... Bcl-2, SUPT3H, SAP130, DNMT3A, SMAD3, MAX, SMAD2, ... Gazin C, Rigolet M, Briand JP, et al., Immunochemical detection of proteins related to the human c-myc exon 1, in EMBO J., vol ... Q Guo, Xie J, Dang C V, Liu E T, Bishop J M, Identification of a large Myc-binding protein that contains RCC1-like repeats (PDF ...
... is caused by a reaction to gliadins and glutenins (gluten proteins) found in wheat, and similar proteins ... "BCL Newsletter. United States Conference of Catholic Bishops. November 2003. Archived from the original on 2 January 2007. ... These are storage proteins rich in proline (prol-) and glutamine (-amin) that dissolve in alcohols and are resistant to ... The vast majority of people with coeliac have one of two types of the HLA-DQ protein. HLA-DQ is part of the MHC class II ...
... which is facilitated by binding to adaptor proteins via protein-protein interaction motifs that are collectively referred to as ... Simple explanation of the mechanisms of apoptosis triggered by internal signals (bcl-2), along the caspase-9, caspase-3 and ... The adaptor protein FADD will recruit (by a Death domain-Death domain interaction) pro-Caspase 8 via the DED domain. This FasR ... These proteins allow caspase-1 activation by forming a multiprotein activating complex called Inflammasomes. For example, a NOD ...
RAR-srodni orfan receptor beta
ATBF1 • BCL (6, 11A, 11B) • CTCF • E4F1 • EGR (2, 3) • ERV3 • GFI1 • GLI-Kruppel familija (1, 2, 3, REST, S2, YY1) • HIC (1, 2) ... Protein kodiran ovim genom je član NR1 potfamilije nuklearnih hormonskih receptora. To je DNA-vezujući protein koji se može ... 2000). "Differential ligand-dependent protein-protein interactions between nuclear receptors and a neuronal-specific cofactor ...
Sterol regulatory element-binding protein
SREB proteins are indirectly required for cholesterol biosynthesis and for uptake and fatty acid biosynthesis. These proteins ... proteins. However, in contrast to E-box-binding HLH proteins, an arginine residue is replaced with tyrosine making them capable ... SREBP precursors are retained in the ER membranes through a tight association with SCAP and a protein of the INSIG family. ... Sterol regulatory element-binding proteins (SREBPs) are transcription factors that bind to the sterol regulatory element DNA ...
protein binding. • ankyrin binding. • gamma-catenin binding. • beta-catenin binding. • GTPase activating protein binding. • ... Oneyama C, Nakano H, Sharma SV (March 2002). "UCS15A, a novel small molecule, SH3 domain-mediated protein-protein interaction ... Several proteins such as SNAI1/SNAIL, ZFHX1B/SIP1, SNAI2/SLUG, TWIST1 and DeltaEF1 have been found ... identical protein binding. Cellular component. • cell-cell adherens junction. • apical junction complex. • trans-Golgi network ...
... adipocyte protein 2 (aP2), a fatty acid binding protein; this may cause macrophages to increase their uptake of these lipids, ... but also promotes its cell survival by stimulating production and of insulin-like growth factor 1 and possibly altering the Bcl ... 13(S)-HpODE, and 13(S)-HODE directly activate human (but not mouse) GPR132 (G protein coupled receptor 132, also termed G2A) in ... Blackburn, Mary L; Podgorski, Izabela; Bull, Arthur W (1999). "Specific protein targets of 13-oxooctadecadienoic acid (13-OXO) ...
... arrest and cellular apoptosis via the accumulation of cytosolic p53 and subsequent activation of Bcl-2-associated X protein, an ...
Farnesoid X receptor
protein binding. • ligand-dependent nuclear receptor binding. • transcription factor activity, RNA polymerase II distal ... "Inactivation of caspase-8 on mitochondria of Bcl-xL-expressing MCF7-Fas cells: role for the bifunctional apoptosis regulator ... Seol W, Choi HS, Moore DD (Jan 1995). "Isolation of proteins that interact specifically with the retinoid X receptor: two novel ... Seol W, Choi HS, Moore DD (Jan 1995). "Isolation of proteins that interact specifically with the retinoid X receptor: two novel ...
Low BC, Lim YP, Lim J, Wong ES, Guy GR (November 1999). "Tyrosine phosphorylation of the Bcl-2-associated protein BNIP-2 by ... protein binding. • thioesterase binding. • protein kinase binding. • nucleotide binding. • GTP binding. • identical protein ... "Protein Data Bank in Europe. EMBL-EBI. Retrieved 2016-04-22.. *^ "CDC42 (cell division cycle 42 (GTP binding protein, 25kDa))" ... Cell division control protein 42 homolog, also known as Cdc42, is a protein involved in regulation of the cell cycle. It was ...
Neuroprotection that is associated with 4-PPBP increases Bcl-2 expression; Bcl-2 expression is regulated by CREB.  ... using a mechanism that activates the transcription factor cyclic adenosine monophosphate response element-binding protein (CREB ... "Sigma receptor agonists provide neuroprotection in vitro by preserving bcl-2". Anesthesia and Analgesia. 104 (5): 1179-84, ... "Cyclic adenosine monophosphate response element-binding protein phosphorylation and neuroprotection by 4-phenyl-1-(4- ...
Bcl-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 ... "Identification of the protein-protein contact site and interaction mode of human VDAC1 with Bcl-2 family proteins". Biochem. ... Bcl-2-associated X protein has been shown to interact with: Bcl-2, BCL2L1, BCL2A1 SH3GLB1, SLC25A4, VDAC1, TCTP, YWHAQ, Bid, ... In addition, it can become activated by binding BCL-2, as well as non-BCL-2 proteins such as p53 and Bif-1. Conversely, BAX can ...
BCL-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 ...
apoptosis 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 ... LSBio BCL2L14 / BCL-G Proteins [LifeSpan BioSciences, Inc.] LSBio BCL2L14 / BCL-G Proteins. LifeSpan BioSciences, Inc. ... 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 ...
Bcl-2 antiapoptotic proteins inhibit Beclin 1-dependent autophagy. - PubMed - NCBI
Thus, Bcl-2 not only functions as an antiapoptotic protein, but also as an antiautophagy protein via its inhibitory interaction ... The anti-apoptotic protein, Bcl-2, interacts with the evolutionarily conserved autophagy protein, Beclin 1. However, little is ... Here, we show that wild-type Bcl-2 antiapoptotic proteins, but not Beclin 1 binding defective mutants of Bcl-2, inhibit Beclin ... Bcl-2 antiapoptotic proteins inhibit Beclin 1-dependent autophagy.. Pattingre S1, Tassa A, Qu X, Garuti R, Liang XH, Mizushima ...
Bcl-2, the Antideath Protein | Science Signaling
Bcl-2 is well known for its role as an antiapoptotic protein, and Pattingre et al. now show that Bcl-2 also inhibits autophagy ... This cell death was inhibited by knockdown of the autophagy protein ATG5 by RNAi. Thus, Bcl-2 appears to be a more general ... In HeLa cells, which endogenously express both beclin 1 and Bcl-2, Bcl-2 and beclin 1 coimmunoprecipitated under nutrient-rich ... The interaction between beclin 1 and Bcl-2 was confirmed in HT-29 cells overexpressing Bcl-2 by coimmmunoprecipitation, and ...
The endoplasmic reticulum in apoptosis and autophagy: role of the BCL-2 protein family | Oncogene
In addition to the regulation of apoptosis, BCL-2 proteins at the ER also regulate autophagy, a survival pathway that limits ... an important role for BCL-2 proteins at the endoplasmic reticulum is now well established. Signaling pathways emanating from ... with particular emphasis on the BCL-2 family proteins. ... and the BCL-2 family is almost invariably implicated in the ... 1997). p28 Bap31, a Bcl-2/Bcl-XL- and procaspase-8-associated protein in the endoplasmic reticulum. J Cell Biol 139: 327-338. ...
Assessment 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. ... BCL-2 proteins Mitochondria Apoptosis Retrotranslocation BH3-only proteins This is a preview of subscription content, log in to ... The retrotranslocation of BCL-2 proteins from the OMM can be measured using fluorescence-labeled protein in intact cells or ...
RCSB PDB - Protein Feature View - Bcl-2-interacting killer - Q13323 (BIK HUMAN)
The PDB archive contains information about experimentally-determined structures of proteins, nucleic acids, and complex ... Association to the apoptosis repressors Bcl-X(L), BHRF1, Bcl-2 or its adenovirus homolog E1B 19k protein suppresses this death- ... Protein Feature View of PDB entries mapped to a UniProtKB sequence * Number of PDB entries for Q13323: no matching PDB entries ... This protein in other organisms (by gene name): Q13323 - Homo sapiens 0 * O70337 - Mus musculus no matching PDB entries ...
BCL-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 ...
Bcor - BCL-6 corepressor - Mus musculus (Mouse) - Bcor gene & protein
May specifically inhibit gene expression when recruited to promoter regions by sequence-specific DNA-binding proteins such as ... to allow unambiguous identification of a protein.,p>,a href=/help/protein_names target=_top>More...,/a>,/p>Protein namesi. ... Pfam protein domain database. More...Pfami. View protein in Pfam. PF12796, Ank_2, 1 hit. PF15808, BCOR, 1 hit. PF16553, ... PROSITE; a protein domain and family database. More...PROSITEi. View protein in PROSITE. PS50297, ANK_REP_REGION, 1 hit. ...
The Bcl-2 Protein Family: Arbiters of Cell Survival | Science
Bcl-2 and related cytoplasmic proteins are key regulators of apoptosis, the cell suicide program critical for development, ... Bcl-2 family members are essential for maintenance of major organ systems, and mutations affecting them are implicated in ... Those most similar to Bcl-2 promote cell survival by inhibiting adapters needed for activation of the proteases (caspases) that ... apparently through mechanisms that include displacing the adapters from the pro-survival proteins. Thus, for many but not all ...
Bcl-2 Family of Proteins in Mice | Cancer Council Victoria
Recombinant Human Ctip1 / BCL-11A protein (ab112415) References
Bcl-2 Family Proteins and Antibodies - Apoptosis and Cell Cycle | Sigma-Aldrich
Bcl-2, Bcl-xL) or promote (e.g. Bax, Bcl-xS, Bak) apoptosis. Bcl-2 inhibits apoptosis by preventing the ... If the Bcl-2 level is higher than the Bax level, apoptosis will be prohibited. The ratio of Bcl-2 to Bax in the cell can ... Some cancer cells, such as melanoma, overexpress Bcl-2 preventing apoptosis and allowing malignant growth to continue.
... Bcl-2 is a member of a large gene family encoding proteins that can either inhibit (e.g. ...
... Bcl-2 is a member of a large gene family encoding proteins that can either inhibit (e.g. ...
Bcl-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. ... The p53/p21 complex regulates cancer cell invasion and apoptosis by targeting Bcl-2 family proteins. Cancer Res 2017;77:3092- ...
c bcl 1 Proteins - Medical Dictionary online-medical-dictionary.org
The Bcl-2 Protein Family: Arbiters of Cell Survival | Science
Hypoxia-Induced Modulation of Apoptosis and BCL-2 Family Proteins in Different Cancer Cell Types
The expression profile of 93 genes involved in apoptosis as well as the protein level of BCL-2 family proteins were then ... Finally, the modulation of the abundance and/or of the post-translational modifications of most proteins of the BCL-2 family by ... hypoxia decreased the abundance of nearly all the pro-apoptotic BCL-2 family proteins while none of them are decreased in A549 ... are important mediators of etoposide-induced cell death in HepG2 cells and the hypoxia-induced modification of these proteins ...
The BCL‐2 Family Proteins - Key Regulators and Effectors of Apoptosis
BCL‐2 was the first cloned component of the mechanism for apoptosis - the process by which metazoan cells commit suicide - to ... Mammals are now known to carry genes for a large number of BCL‐2 like proteins, some of which, like BCL‐2 itself, inhibit ... and Bok (middle, purple symbol) and BH3‐only proteins (top, green symbol). All BCL‐2 family members bear a number of BCL‐2 ... BH3 peptide fits into a hydrophobic groove on the surface of Bcl‐x. The BH3 of Bcl‐x itself is coloured green. Note that Bcl‐x ...
How the Bcl-2 family of proteins interact to regulate apoptosis
Its three sub-families have distinct roles: the BH3-only proteins trigger apoptosis by binding via their BH3 domain to pro- ... Commitment of cells to apoptosis is governed largely by protein-protein interactions between members of the Bcl-2 protein ... Commitment of cells to apoptosis is governed largely by protein-protein interactions between members of the Bcl-2 protein ... How the Bcl-2 family of proteins interact to regulate apoptosis Cell Res. 2006 Feb;16(2):203-13. doi: 10.1038/sj.cr.7310028. ...
Proto-Oncogene Proteins c-bcl-2 | Journal of Virology
Induces the Nucleolar Targeting of the Kaposis Sarcoma-Associated Herpesvirus KS-Bcl-2 Protein Inna Kalt, Tatyana Borodianskiy ... Vesicular Stomatitis Virus Induces Apoptosis Primarily through Bak Rather than Bax by Inactivating Mcl-1 and Bcl-XL Alicia F. ... Bcl-2 Blocks Accretion or Depletion of Stored Calcium but Has No Effect on the Redistribution of IP3 Receptor I Mediated by ... Epstein-Barr Virus-Encoded Bcl-2 Homologue Functions as a Survival Factor in Wp-Restricted Burkitt Lymphoma Cell Line P3HR-1 ...
Bcl-2 Protein Targeting by the p53/p21 Complex-Letter | Cancer Research
Bcl-2 Protein Targeting by the p53/p21 Complex-Letter. Liz J. Hernandez Borrero, Rahmat Sikder, Amriti Lulla, Prashanth Gokare ... Bcl-2 Protein Targeting by the p53/p21 Complex-Letter. Liz J. Hernandez Borrero, Rahmat Sikder, Amriti Lulla, Prashanth Gokare ... Bcl-2 Protein Targeting by the p53/p21 Complex-Letter. Liz J. Hernandez Borrero, Rahmat Sikder, Amriti Lulla, Prashanth Gokare ... Bcl-2 Protein Targeting by the p53/p21 Complex-Letter Message Subject (Your Name) has forwarded a page to you from Cancer ...
SIRT1 Suppresses Breast Cancer Growth Through Downregulation of the Bcl-2 Protein
Expression of Bcl-2 Family Proteins in the Ovarian Follicular Apparatus in the Acute Period after Experimental Hyperthermia |...
... was analyzed and Bcl-2/Bad ratio in the follicular apparatus of the rat ovary was determined on day... ... proapoptotic protein Bad and anti-apoptotic protein Bcl-2) ... proapoptotic protein Bad and anti-apoptotic protein Bcl-2) was ... Expression of Bcl-2 Family Proteins in the Ovarian Follicular Apparatus in the Acute Period after Experimental Hyperthermia. ... intensity of immunohistochemical staining for Bad protein against the background of more pronounced expression of Bcl-2 protein ...
Role of Bcl-2 pro-survival proteins in melanoma
... Metastatic melanoma is one of ... There is some evidence that Bcl-2 pro-survival proteins (which normally keep cells alive by inhibiting the cell death program ... Our research aims to identify the key Bcl-2 pro-survival proteins that are responsible for melanoma survival. This will be ... Our hypothesis is that Bcl-2 pro-survival proteins provide a survival advantage for melanomas and might contribute to ...
bcl-2-Associated X Protein | Harvard Catalyst Profiles | Harvard Catalyst
A member of the Bcl-2 protein family and homologous partner of C-BCL-2 PROTO-ONCOGENE PROTEIN. It regulates the release of ... "bcl-2-Associated X Protein" by people in Harvard Catalyst Profiles by year, and whether "bcl-2-Associated X Protein" was a ... "bcl-2-Associated X Protein" is a descriptor in the National Library of Medicines controlled vocabulary thesaurus, MeSH ( ... Below are the most recent publications written about "bcl-2-Associated X Protein" by people in Profiles. ...
Investigating the requirement of pro-survival Bcl-2 family proteins in leukaemia | Cancer Council Victoria
Bok is a pro-apoptotic Bcl-2 protein with restricted expression in reproductive tissues and heterodimerizes with selective anti...
... the Bcl-2-related proteins can be separated into anti-apoptotic (Bcl-2, Bcl-xL, Mcl-1, Bcl-w, and Bfl-1/A1) and pro-apoptotic ... 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, and Bcl-w) anti-apoptotic proteins. Coupled with findings showing that Bok-induced apoptosis could only be ... A) Sequence alignment of Bok with several members of the Bcl-2 family proteins. The ORF for Bok predicts a protein of 213 amino ...
Increase in Bcl-2 phosphorylation and reduced levels of BH3-only Bcl-2 family proteins in kainic acid-mediated neuronal death...
Integrated strategy reveals the protein interface between cancer targets Bcl-2 and NAF-1. | Sigma-Aldrich
Among the proteins involved in this response are nutrient-deprivation autophagy factor-1 (NAF-1)- and Bcl-2. NAF-1 is a ... NAF-1 binds to both the pro- and antiapoptotic regions (BH3 and BH4) of Bcl-2, as demonstrated by a nested protein fragment ... A combination of the solution studies together with a new application of DCA to the eukaryotic proteins NAF-1 and Bcl-2 ... Integrated strategy reveals the protein interface between cancer targets Bcl-2 and NAF-1.. [Sagi Tamir, Shahar Rotem-Bamberger ...
ApoptosisApoptoticInhibitionGeneOverexpressionMitochondriaExpressionCellsInteractsSurvivalInteractionCaspasesCytochromeInteractionsMitochondrial outer membraneRegulatorsPhosphorylationCytoplasmicEvolutionarily conservedProsurvival Bcl-2 familyMotifs known as Bcl-2 homologyBCL2Outer mitochonHeterodimerizationInhibitorHeterodimersOncogenePathwayCellularAutophagyGenesMRNAProapoptotic proteinsPeptidesAntibodiesFamily membersComplexTargetsMembersPathwaysAntagonistsFollicularAntiapoptotic activityMoleculesEndoplasmic reticulumConformationalRegulatorRelease of apoptogenic proteinsTumorLymphoma
- Apoptosis regulator BAX, also known as bcl-2-like protein 4, is a protein that in humans is encoded by the BAX gene. (wikipedia.org)
- The expression of BAX is upregulated by the tumor suppressor protein p53, and BAX has been shown to be involved in p53-mediated apoptosis. (wikipedia.org)
- This protein family, which provides the framework for controlling apoptosis, takes its name from a type of cancer called B-cell lymphoma. (britannica.com)
- Ubiquitin-like protein MNSFβ covalently binds to Bcl-G and enhances lipopolysaccharide/interferon γ-induced apoptosis in macrophages. (nih.gov)
- Although initially identified as central regulators of apoptosis at the level of mitochondria, an important role for BCL-2 proteins at the endoplasmic reticulum is now well established. (nature.com)
- Signaling pathways emanating from the endoplasmic reticulum (ER) are involved in apoptosis initiated by stimuli as diverse as ER stress, oncogene expression, death receptor (DR) ligation and oxidative stress, and the BCL-2 family is almost invariably implicated in the regulation of these pathways. (nature.com)
- In addition to the regulation of apoptosis, BCL-2 proteins at the ER also regulate autophagy, a survival pathway that limits metabolic stress, genomic instability and tumorigenesis. (nature.com)
- BCL-2 proteins control stress-dependent commitment to the programmed cell death apoptosis. (springer.com)
- Martinou J-C, Youle RJ (2011) Mitochondria in apoptosis: Bcl-2 family members and mitochondrial dynamics. (springer.com)
- Association to the apoptosis repressors Bcl-X(L), BHRF1, Bcl-2 or its adenovirus homolog E1B 19k protein suppresses this death-promoting activity. (rcsb.org)
- Bcl-2 and related cytoplasmic proteins are key regulators of apoptosis, the cell suicide program critical for development, tissue homeostasis, and protection against pathogens. (sciencemag.org)
- More distant relatives instead promote apoptosis, apparently through mechanisms that include displacing the adapters from the pro-survival proteins. (sciencemag.org)
- Bax, Bcl-x S , Bak) apoptosis. (sigmaaldrich.com)
- Bcl-2 inhibits apoptosis by preventing the release of Apoptosis Inducing factor (AIF) and cytochrome c from mitochondria. (sigmaaldrich.com)
- If the Bcl-2 level is higher than the Bax level, apoptosis will be prohibited. (sigmaaldrich.com)
- The ratio of Bcl-2 to Bax in the cell can determine whether or not the cell initiates apoptosis or survives. (sigmaaldrich.com)
- Some cancer cells, such as melanoma, overexpress Bcl-2 preventing apoptosis and allowing malignant growth to continue. (sigmaaldrich.com)
- BCL‐2 was the first cloned component of the mechanism for apoptosis - the process by which metazoan cells commit suicide - to be recognized. (els.net)
- Mammals are now known to carry genes for a large number of BCL‐2 like proteins, some of which, like BCL‐2 itself, inhibit apoptosis, and others that promote or are required for apoptosis. (els.net)
- Direct interactions between BCL‐2 family members are essential for the proper regulation and implementation of apoptosis during development and for homoeostasis. (els.net)
- Abnormalities to the regulation of cell death, such as those caused by mutations to genes for BCL‐2 family members prevent apoptosis occurring when it should, and can lead to diseases including cancer. (els.net)
- According to this model, apoptosis can be triggered by increasing the concentration of BH3‐only proteins, adding an artificial BCL‐2 antagonist, or depleting the cells of antiapoptotic BCL‐2 family members. (els.net)
- Commitment of cells to apoptosis is governed largely by protein-protein interactions between members of the Bcl-2 protein family. (nih.gov)
- Its three sub-families have distinct roles: the BH3-only proteins trigger apoptosis by binding via their BH3 domain to pro-survival relatives, while the pro-apoptotic Bax and Bak have an essential downstream role involving disruption of organellar membranes and induction of caspase activation. (nih.gov)
- Kim and colleagues reported a p53/p21 complex regulates cancer cell invasion and apoptosis by targeting the Bcl-2 family ( 1 ). (aacrjournals.org)
- The expression of apoptosis regulators (proapoptotic protein Bad and anti-apoptotic protein Bcl-2) was analyzed and Bcl-2/Bad ratio in the follicular apparatus of the rat ovary was determined on day 3 after hyperthermia (rectal temperature 43.5°C). Hyperthermia in the catabolic phase leads to different degrees of activation of the molecular "switches" of apoptosis in cells of ovarian follicular epithelium. (springer.com)
- On day 3 after exposure to hyperthermia, Bcl-2/Bad ratio increased, which reflects antiapoptotic protection of cells and conditions for blockade of mitochondrial pathway of apoptosis in the follicular apparatus of the ovaries during the acute period after hyperthermia. (springer.com)
- There is some evidence that Bcl-2 pro-survival proteins (which normally keep cells alive by inhibiting the cell death program of apoptosis) are expressed at unusually high levels in melanoma compared to normal melanocytes. (edu.au)
- Identification of Bok as a new pro-apoptotic Bcl-2 protein with restricted tissue distribution and heterodimerization properties could facilitate elucidation of apoptosis mechanisms in reproductive tissues undergoing hormone-regulated cyclic cell turnover. (pnas.org)
- The Bcl-2 family of proteins that consists of different anti- and pro-apoptotic members is important in the "decision" step of apoptosis ( 3 ). (pnas.org)
- Overexpression of Bcl-2 suppresses apoptosis induced by a variety of agents both in vitro and in vivo ( 10 ). (pnas.org)
- It has also been found that the anti-apoptotic effect of Bcl-2 is not universal because Bcl-2 overexpression is not effective in blocking Fas-mediated apoptosis and the apoptosis of autoreactive thymocytes during negative selection ( 13 , 14 ). (pnas.org)
- The specific integrated approach described in this paper provides the first structural information, to our knowledge, for future targeting of the NAF-1-Bcl-2 complex in the regulation of apoptosis/autophagy in cancer biology. (sigmaaldrich.com)
- A key event in the regulation of apoptosis is the heterodimerization between anti-apoptotic and pro-apoptotic family members, which involves a conserved surface-exposed groove on the anti-apoptotic proteins. (rcsb.org)
- The Bcl-2 protein blocks a distal step in an evolutionarily conserved pathway for programmed cell death and apoptosis. (springer.com)
- The BCL-2 family of proteins constitutes a critical control point in apoptosis residing immediately upstream of irreversible cellular damage, where family members control the release of apoptogenic factors from mitochondria. (aacrjournals.org)
- BCL-2 family proteins regulate MOMP and thereby determine the cellular commitment to apoptosis. (aacrjournals.org)
- Hepatocyte growth factor suppresses tumor cell apoptosis in nasopharyngeal carcinoma by upregulating Bcl-2 protein expression. (biomedsearch.com)
- In this study, we aimed at determining whether HGF is a potent inhibitor of cell apoptosis in NPC, and tried to find out which antiapoptotic or proapoptotic protein is involved in this process. (biomedsearch.com)
- NPC cells were treated with HGF (25 ng/ml), followed by an assay for cell viability and apoptosis, as well as by an expression analysis of Bcl-2 and Bax using immunostaining and Western blot. (biomedsearch.com)
- In vitro, exogenous HGF was found to promote cell growth, to suppress cell apoptosis and to upregulate the expression of Bcl-2 in NPC cells without EBV infection. (biomedsearch.com)
- HGF is a potent inhibitor of cell apoptosis in NPC by upregulating Bcl-2 through both autocrine and paracrine EBV-independent pathways. (biomedsearch.com)
- The aim of this study was to investigate the role, mechanism of action and clinical significance of these proteins in neuron apoptosis and functional impairment following cerebral ischemia̸reperfusion injury in rats. (spandidos-publications.com)
- Nerve cell apoptosis may occur following cerebral ischemia or reperfusion injury as a result of the expression of apoptosis-related proteins and a complicated process leading to physiological and pathological alterations. (spandidos-publications.com)
- Those studies also demonstrated that the expressed Bax activated caspase-3, indirectly inhibited Bcl-2 expression, formed Bax-Bcl-2 heterodimers and initiated cell apoptosis following cerebral ischemia/reperfusion injury. (spandidos-publications.com)
- The present study investigated the expression of caspase-3, Bcl-2 and Bax and neuron apoptosis, as well as the ethological alterations following cerebral ischemia-reperfusion injury in a rat model. (spandidos-publications.com)
- However, unlike the caspase cleavage products of cellular Bcl-2, Bcl-x L , and Bid, which are potent inducers of apoptosis, the cleavage product of γHV68 Bcl-2 lacked proapoptotic activity. (asm.org)
- Tsujimoto, Y. Role of Bcl-2 family proteins in apoptosis: apoptosomes or mitochondria. (springer.com)
- For instance, AS of the BCL-X gene balances cell survival and apoptosis in development and cancer. (unboundmedicine.com)
- Thus, E6 expression results in the loss of p53 function in cells, including stimulation of apoptosis and inhibition of the expression of the antiapoptotic protein bcl-2. (aacrjournals.org)
- We show in this study that protein kinase C (PKC)-θ is required for enhancing the survival of activated CD4 + T cells by up-regulating Bcl-x L . In response to TCR stimulation, CD4 + PKC-θ −/− T cells failed to up-regulate Bcl-x L , and underwent accelerated apoptosis via a caspase- and mitochondria-dependent pathway. (jimmunol.org)
- Forced expression of Bcl-x L was sufficient to inhibit apoptosis observed in PKC-θ knockdown cells. (jimmunol.org)
- In addition, activated T cells substantially up-regulate Bcl-x L that intrinsically increases the ability of resistance to apoptosis ( 2 , 5 , 6 ). (jimmunol.org)
- Important advances in understanding T cell apoptosis have come through the study of Bcl-2 family members. (rupress.org)
- Several studies have demonstrated that overexpression of Bcl-2 ( 10 )( 11 ) or Bcl-X L ( 12 )( 13 ) in thymocytes confers resistance to spontaneous apoptosis and apoptosis induced by a variety of death stimuli. (rupress.org)
- Conversely, overexpression of death-promoting proteins Bax ( 14 ) or BAD ( 15 ) in thymocytes accelerates cell death in response to apoptosis-inducing stimuli. (rupress.org)
- Proteins of the Bcl-2 family are critical regulators of apoptosis, but how its BH3-only members activate the essential effectors Bax and Bak remains controversial. (rupress.org)
- Prosurvival members of the Bcl-2 family (Bcl-2, Bcl-x L , Bcl-w, Mcl-1, and A1) prevent Bax/Bak activation and thereby preclude MOMP and apoptosis. (rupress.org)
- Bag-1 was first cloned from mouse cells as a novel protein which interacts with Bcl-2 and Bcl-X L , enhancing the ability of Bcl-2 to prevent apoptosis. (scielo.br)
- Most pro-survival members, which can inhibit apoptosis in the face of a wide variety of cytotoxic insults, contain at least BH1 and BH2, and those most similar to Bcl-2 have all four BH domains. (acris-antibodies.com)
- B-cell lymphocyte/leukemia 2 (Bcl-2) family proteins are important regulators of apoptosis. (eurekaselect.com)
- In this study, we used a similar cell culture model system of matched primary and metastatic melanoma cells from the same patient to investigate whether p53 and bcl-2 family proteins were involved in atRA-induced apoptosis. (diva-portal.org)
- These data indicate that p53, p21, bax and bcl-2 proteins were involved in atRA-induced apoptosis in melanoma cells. (diva-portal.org)
- The BH3-only members of the Bcl-2 protein family are essential initiators of programmed cell death and are required for apoptosis induced by cytotoxic stimuli. (biologists.org)
- Amongst the members of the Bcl-2 family, the BH3-only proteins have now been recognised as essential initiators of programmed cell death and stress-induced apoptosis ( Huang and Strasser, 2000 ). (biologists.org)
- This review focuses on the `Bcl-2-regulated pathway', particularly on the role of the BH3-only proteins in the apoptosis signalling cascade. (biologists.org)
- The antiapoptotic members of the Bcl-2 protein family (Bcl-2, Bcl-X L , and Mcl-1) are important inhibitors of apoptosis, but have not been investigated extensively in cholangiocarcinoma. (bmj.com)
- By prolonging survival through blocking apoptosis, these proteins might be reducing the efficacy of cytotoxic anticancer treatments in cholangiocarcinoma. (bmj.com)
- 13, 14 The Bcl-2 protein family plays a central part in the control of apoptosis. (bmj.com)
- 15, 16 Bcl-2, a 52 kDa protein, is the prototype of this family, and inhibits the induction of apoptosis. (bmj.com)
- High concentrations of Bcl-2 or Bcl-X L affect the susceptibility of a cell to the induction of apoptosis by altering the ratio of death promoters to suppressors, providing tumour cells with a survival advantage, and permitting expansion of transformed cells harbouring mutations within their genome. (bmj.com)
- In this study, we demonstrate that ABT-263, a potent and orally bioavailable inhibitor of the Bcl-2 family, was able to reverse the resistance of hepatocarcinoma cell lines to TRAIL-induced apoptosis, while sparing normal liver cells. (springermedizin.de)
- The molecular mechanism of the reversal in resistance may be attributed to the inhibition by ABT-263 of anti-apoptosis proteins of the Bcl-2 family. (springermedizin.de)
- The aims of this study were to assess the expression levels of three proteins involved in apoptosis--Bcl-2, Bcl-X, and Bax--and evaluate their relationship with clinicopathologic features and survival in oral squamous cell carcinoma (OSCC). (semanticscholar.org)
- Cell viability measures, expression of proteins implicated in apoptosis and MAPK/PI3K-AKT/mTOR pathway signaling, and profiling of composite kinase activities were undertaken in a panel of 14 cell lines. (biomedcentral.com)
- Hypoxic KRAS/PIK3CA -mutant HCT-116 and HCT-15 cell lines (both with low endogenous expression of the anti-apoptotic Mcl-1 protein and showing augmented inhibition of viability following the addition of ABT-737 to AZD8055) responded to combo-Rx by induction of apoptosis but with the simultaneous strong Mcl-1 up-regulation and activation of MAPK/PI3K-conducted signaling. (biomedcentral.com)
- The proteins of the Bcl-2 family are important regulators of apoptosis, or programmed cell death. (inserm.fr)
- The Us3 protein kinase of herpes simplex virus 1 blocks apoptosis and induces phosporylation of the Bcl-2 family member Bad. (semanticscholar.org)
- The herpes simplex virus 1 (HSV-1) Us3 open-reading frame encodes a serine/threonine protein kinase that participates in the inhibition of apoptosis induced by virus infection and other stress agents. (semanticscholar.org)
- The pseudorabies virus US3 protein kinase possesses anti-apoptotic activity that protects cells from apoptosis during infection and after treatment with sorbitol or staurosporine. (semanticscholar.org)
- Carnitine palmitoyltransferase 1a (Cpt1a), the rate-limiting enzyme for fatty acid β-oxidation, directly interacted with Bcl-2 by binding to its BH3 domain, which anchored Bcl-2 in the mitochondria to attenuate apoptosis. (nature.com)
- Lung macrophages from IPF subjects had a direct correlation between CPT1A and Bcl-2, whereas the absence of binding induced apoptosis. (nature.com)
- Bcl-2 and Bcl-X L , two members of the Bcl-2 family, function as apoptosis inhibitors and are considered homologs of the nematode CED-9 ( 15 ). (pnas.org)
- However, the precise mechanism by which Bcl-2 and Bcl-X L control caspase activation and apoptosis remains controversial. (pnas.org)
- Isoform Bcl-X(S) promotes apoptosis. (abcam.com)
- Aim: Our aim was to evaluate the role of Bax and Bcl-2 apoptosis- related proteins in the carcinogenesis of the stomach. (openarchives.gr)
- Proteins of the BCL-2 family control the mitochondrial pathway of apoptosis. (immune-source.com)
- INHIBITORS OF PROSURVIVAL BCL-2 PROTEINS Small organic molecules Obatoclax This synthetic indol bipyrrole molecule derived from the natural product prodigiosin is capable of binding to all prosurvival BCL-2 family proteins with low affinity (in the M range) and inducing apoptosis in tumor cells . (immune-source.com)
- TW-37, a rationally designed benzoylsulphonyl analog of gossypol [22, 27], was also known to operate only in part as a pan-BH3 mimetic: it binds to BCL-2, BCL-XL and MCL-1 with moderate affinity (sub-M), induces apoptosis depending partially on BAX/BAK activation and shows several off-target effects. (immune-source.com)
- However, a recent careful analysis has demonstrated that TW-37 (i) induces several typical features of mitochondrial apoptosis in MCL-1-dependent cells [but not BCL-2 or BCL-XL-dependent cells] and (ii) exhibits all the hallmarks of a NOXA-like BH3 mimetic antagonizing selectively MCL-1, although only at high concentrations . (immune-source.com)
- The direct role of Bcl-x L in chemoresistance was demonstrated by the use of Bcl-x L -overexpressing Ramos cells, Ramos hemagglutinin (HA)-Bcl-x, which were not sensitized by rituximab to drug-induced apoptosis. (jimmunol.org)
- However, inhibition of Bcl-x L in Ramos HA-Bcl-x resulted in sensitization to drug-induced apoptosis. (jimmunol.org)
- Ramos HA-Bcl-x cells were as sensitive as the wild type to CH-11-induced apoptosis. (jimmunol.org)
- We assessed the expression of Bcl-2 family members at both mRNA and protein levels as well as the Caspase-3 activity, in order to investigate the occurrence of apoptosis in hippocampus of STZ-induced diabetic rats. (hindawi.com)
- Several factors are contributed in apoptosis, but the key elements are categorized in two main families of proteins including caspase enzymes and Bcl-2 family [ 18 ]. (hindawi.com)
- Bcl-2 family is a set of cytoplasmic proteins that regulate apoptosis. (hindawi.com)
- The two main groups of this family, Bcl-2 and Bax proteins, are functionally opposed: Bcl-2 and Bcl-x L act to inhibit apoptosis, whereas Bax counteracts this effect [ 19 , 20 ]. (hindawi.com)
- p53 interacts with the anti-apoptotic proteins, Bcl-2/XL, and induces mitochondria-mediated apoptosis. (ntu.edu.sg)
- Taken altogether, our results revealed a structural basis for a conserved binding mechanism between p53DBD and the anti-apoptotic Bcl-2 family proteins, which shed light on to the molecular understanding of the transcription-independent apoptosis pathway of p53. (ntu.edu.sg)
- Prof. Green has made fundamental contributions to our understanding of activation-induced apoptosis in T cells, the role of the oncogene Myc in driving apoptosis, the ability of BCL-2 proteins to block cell death, the functions of death receptors in cell death and the immune system, and the mitochondrial pathway of apoptosis-publishing over 400 papers along the way. (cshlpress.org)
- In conclusion, dietary NiCl 2 in excess of 300 mg/kg caused apoptosis, altered Bax, Bcl-2 and Caspase-3 mRNA expression levels and contents, and induced oxidative stress in the spleen. (mdpi.com)
- Also, splenocyte apoptosis was closely related to the alternations of Bax, Bcl-2 and Caspase-3 mRNA expression, and oxidative damage. (mdpi.com)
- Huang J, Cui H, Peng X, Fang J, Zuo Z, Deng J, Wu B. The Association between Splenocyte Apoptosis and Alterations of Bax, Bcl-2 and Caspase-3 mRNA Expression, and Oxidative Stress Induced by Dietary Nickel Chloride in Broilers. (mdpi.com)
- A 25 kDa inner mitochondrial membrane protein which inhibits apoptosis, thus increasing the survival of cells (good or bad). (thefreedictionary.com)
- Antisense nucleotide sequences (oligonucleotides) targeted at BCL-2 messenger RNA reduces the expression of BCL-2 and increases apoptosis in these tumours with clinical improvement. (thefreedictionary.com)
- These cells can resist apoptosis through mechanisms such as the regulation of Bcl-2. (aacrjournals.org)
- It has been proven that stem cells can resist apoptosis through a variety of mechanisms, including the regulation of Bcl-2, whereas non-tumourigenic cells in tumours are more susceptible to the induction of apoptosis or chemotherapy ( 7 - 9 ). (aacrjournals.org)
- In addition, the withdrawal of IL-3 from the bcl-x L overexpressing cells, but not control cells, leads to the rapid loss of FLAP even though these cells, in contrast to control cells, do not undergo apoptosis (Datta et al. (elsevier.com)
- Given the absence of apoptosis in bcl-x L cells, it appears that protease activation is an effect that can accompany a variety of cellular perturbations. (elsevier.com)
- Inhibition of NF-kappaB-dependent Bcl-xL expression by clusterin promotes albumin-induced tubular cell apoptosis. (uchicago.edu)
- Petrella A, Ercolino SF, Festa M, Gentilella A, Tosco A, Conzen SD, Parente L. Dexamethasone inhibits TRAIL-induced apoptosis of thyroid cancer cells via Bcl-xL induction. (uchicago.edu)
- One family of proteins involved in the regulation of apoptosis is that of B-cell lymphoma protein 2 (Bcl-2). (physiology.org)
- Complex interactions among the three subgroups within the Bcl-2 family [the antiapoptotic, the multidomain proapoptotic, and the Bcl-2 homology domain 3 (BH3)-only members] control the signaling events of apoptosis upstream of mitochondrial outer membrane permeabilization. (physiology.org)
- Collectively, the Bcl-2 protein family monitors incoming stress signals and orchestrates the initiation of the mitochondrial or intrinsic pathway to apoptosis. (physiology.org)
- Phosphorylation of Bcl-2 in melanoma cells prevents its interaction with proapoptotic Bax, thereby promoting apoptosis. (aacrjournals.org)
- Poon AP, Benetti L, Roizman B. U(S)3 and U(S)3.5 protein kinases of herpes simplex virus 1 differ with respect to their functions in blocking apoptosis and in virion maturation and egress. (uchicago.edu)
- FAM3B/PANDER is a novel cytokine-like protein that induces apoptosis in insulin-secreting beta-cells. (springermedizin.de)
- Prolyl hydroxylase 3 interacts with Bcl-2 to regulate doxorubicin-induced apoptosis in H9c2 cells. (biomedsearch.com)
- Thus, PHD3 upregulation may be partially responsible for DOX-induced cardiomyocyte apoptosis via its interaction with Bcl-2. (biomedsearch.com)
- Mitochondrial benzodiazepine receptor (mBzR) ligands have been shown to reverse Bcl-2 action and facilitate apoptosis. (bmj.com)
- This is the first study to demonstrate that functional antagonism of coexpressed Bcl-X L and Mcl-1 proteins using the mBzR antagonist Pk11195 can facilitate apoptosis in cholangiocarcinoma following chemotherapy and radiotherapy. (bmj.com)
- Membrane proteins encoded by the BCL-2 GENES and serving as potent inhibitors of cell death by APOPTOSIS. (rush.edu)
- DZNep represses Bcl-2 expression and modulates apoptosis sensitivity in response to Nutlin-3a. (rush.edu)
- The anti-apoptotic protein Bcl-x L is the ultimate effector regulating the survival of CD4 + CD8 + thymocytes subject to the selection process, and the deletion of Bcl-x L leads to premature apoptosis of thymocytes prior to the completion of the developmental process. (hindawi.com)
- In the absence of Bcl-x L , mature T cells undergo apoptosis prior to the completion of the differentiation process to become effector cells. (hindawi.com)
- Bcl-x L is an anti-apoptotic member of the Bcl-2 family of apoptosis regulators. (hindawi.com)
- The BCL2 associated agonist of cell death (BAD) protein is a pro-apoptotic member of the Bcl-2 gene family which is involved in initiating apoptosis. (wikipedia.org)
- After activation, it is able to form a heterodimer with anti-apoptotic proteins and prevent them from stopping apoptosis. (wikipedia.org)
- Dephosphorylated BAD forms a heterodimer with Bcl-2 and Bcl-xL, inactivating them and thus allowing Bax/Bak-triggered apoptosis. (wikipedia.org)
- This leaves Bcl-2 free to inhibit Bax-triggered apoptosis. (wikipedia.org)
- This protein forms a heterodimer with BCL2, and functions as an apoptotic activator. (wikipedia.org)
- The BAX gene was the first identified pro-apoptotic member of the Bcl-2 protein family. (wikipedia.org)
- The anti-apoptotic protein, Bcl-2, interacts with the evolutionarily conserved autophagy protein, Beclin 1. (nih.gov)
- This review provides an overview of ER-associated apoptotic and autophagic signaling pathways, with particular emphasis on the BCL-2 family proteins. (nature.com)
- This finding highlights both an additional connection between apoptotic and autophagic pathways and a novel role for BCL-2 family proteins at the ER. (nature.com)
- Intact BH3 motif is required by BIK, BID, BAK, BAD and BAX for their pro-apoptotic activity and for their interaction with anti-apoptotic members of the Bcl-2 family. (rcsb.org)
- In healthy (non‐apoptotic) cells, only small amounts of antiapoptotic BCL ‐2 members need to be bound to BAX and BAK at any one time. (els.net)
- In the intracellular death program, hetero- and homodimerization of different anti- and pro-apoptotic Bcl-2-related proteins are critical in the determination of cell fate. (pnas.org)
- From a rat ovarian fusion cDNA library, we isolated a new pro-apoptotic Bcl-2 gene, Bcl-2-related ovarian killer (Bok). (pnas.org)
- Bok had conserved Bcl-2 homology (BH) domains 1, 2, and 3 and a C-terminal transmembrane region present in other Bcl-2 proteins, but lacked the BH4 domain found only in anti-apoptotic Bcl-2 proteins. (pnas.org)
- In the yeast two-hybrid system, Bok interacted strongly with some (Mcl-1, BHRF1, and Bfl-1) but not other (Bcl-2, Bcl-xL, and Bcl-w) anti-apoptotic members. (pnas.org)
- This finding is in direct contrast to the ability of other pro-apoptotic members (Bax, Bak, and Bik) to interact with all of the anti-apoptotic proteins. (pnas.org)
- Cell killing induced by Bok was also suppressed following coexpression with Mcl-1 and BHRF1 but not with Bcl-2, further indicating that Bok heterodimerized only with selective anti-apoptotic Bcl-2 proteins. (pnas.org)
- Through heterodimerization, the balance between pro- and anti-apoptotic Bcl-2 proteins presumably determines the cell fate ( 3 , 13 ). (pnas.org)
- BCL-W is a member of the BCL-2 family of anti-apoptotic proteins. (rcsb.org)
- Crystal structures of the ligand binding-competent conformation exist for all anti-apoptotic family members, with the exception of BCL-W, due to the flexibility of the BCL-W groove region. (rcsb.org)
- Existing structures had suggested major deviations of the BCL-W groove region from the otherwise structurally highly related remaining anti-apoptotic family members. (rcsb.org)
- Due to the importance of the anti-apoptotic BCL-2 family as drug targets, the presented crystal structure of ligand binding-competent BCL-W may serve as a valuable basis for structure-based drug design in the future and provides a missing piece for the structural characterization of this protein family. (rcsb.org)
- In contrast, deletion of the BH4 domain of Bcl-2 nullifies anti-apoptotic function and homodimerization, but does not impair binding to the pro-apoptotic protein Bax. (springer.com)
- Taken together, the data suggest the possibility that both Bcl-2/Bcl-2 homodimerization and Bcl-2/Bax heterodimerization are necessary but insufficient for the anti-apoptotic function of the Bcl-2 protein. (springer.com)
- The emerging picture is that of an intricate cellular machinery orchestrated by tightly regulated molecular interactions and conformational changes within BCL-2 family proteins that ultimately govern the cellular commitment to apoptotic death. (aacrjournals.org)
- 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)
- Strong expression of HGF in tumor cells and stromal cells was significantly associated with decreased apoptotic index, advanced clinical stage, lymph node metastasis and high-expression of Bcl-2. (biomedsearch.com)
- The Bcl-2 homologs encoded by herpesvirus saimiri, Epstein-Barr virus, and BHV4 were not cleaved by apoptotic cell extracts and did not possess latent proapoptotic activities. (asm.org)
- Shimizu, S., Shinohara, Y. and Tsujimoto, Y. Bax and Bcl-xL independently regulate apoptotic changes of yeast mitochondria that require VDAC but not adenine nucleotide translocator. (springer.com)
- Overexpression of PTBP1 promotes selection of the distal 5' splice site in BCL-X exon 2, generating the pro-apoptotic BCL-Xs splice variant. (unboundmedicine.com)
- Conversely, depletion of PTBP1 enhanced splicing of the anti-apoptotic BCL-XL variant. (unboundmedicine.com)
- Bcl-2 homology-3 domain (BH3)-only proteins are pro-apoptotic members of the Bcl-2 family whose enhanced expression acts as a trigger for the intrinsic apoptotic cascade. (frontiersin.org)
- The upregulation of a specific subset of BH3-only proteins, including Bid, DP5/Hrk, and BNip3L, in reactive astrocytes suggests that these proteins may execute a novel non-apoptotic function within astrocytes to promote ALS disease progression, thus providing a new potential target for therapeutic intervention. (frontiersin.org)
- The two pro-apoptotic subfamilies differ markedly in their relatedness to Bcl-2. (acris-antibodies.com)
- Antagonists Against Anti-Apoptotic Bcl-2 Family Proteins for Cancer Treatment. (eurekaselect.com)
- Numerous studies have demonstrated that over-expressing anti-apoptotic Bcl-2 proteins is one mechanism for cancer cells to acquire resistance against cancer chemotherapies, suggesting antagonizing these proteins would be a potential approach to overcoming such drug resistance. (eurekaselect.com)
- Jignesh M. Doshi and Chengguo Xing, " Antagonists Against Anti-Apoptotic Bcl-2 Family Proteins for Cancer Treatment. (eurekaselect.com)
- Our findings indicate that the major apoptotic protein Bcl-2 might have a hitherto unrecognized role in the protection of normal muscle. (diva-portal.org)
- A recent study demonstrated the lack of beta-amyloid (Aβ) plaque formation and accumulation of the amyloid precursor protein (APP) in a triple transgenic mouse model of Alzheimer's disease (3xTg-AD) following overexpression of the anti-apoptotic protein, Bcl-2 (Rohn et al. (pubmedcentralcanada.ca)
- The generation and characterization of 3xTgAD mice that overexpress the anti-apoptotic protein, Bcl-2, have been described previously [ 8 ]. (pubmedcentralcanada.ca)
- In response, they unleash the apoptotic cascade by inactivating the protective function of the pro-survival members of the Bcl-2 family and by activating the Bax/Bax-like pro-apoptotic family members. (biologists.org)
- According to their structure and biochemical function (see below), the pro-apoptotic Bcl-2 family members can be divided into two subgroups. (biologists.org)
- Mor … More eover, intracellular acidification, translocation of Bax, a pro-apoptotic protein, from cytosol to mitochondria, opening of mitochondrial permeability transition pore, loss of mitochondrial membrane potential, cytochrome c release from mitochondria into cytosol, and activation of caspase-9 and 3 were observed in a pH-dependent fashion. (nii.ac.jp)
- Zurück zum Zitat Adams JM, Cory S (2007) The Bcl-2 apoptotic switch in cancer development and therapy. (springermedizin.de)
- Since CRC comprises heterogeneous tumors with predominant hypoxic components, we investigated effects of an inhibitor of anti-apoptotic Bcl-2 family proteins (ABT-737) in combination with an mTOR inhibitor (AZD8055)-collectively referred to as combo-Rx, in hypoxic CRC cell lines. (biomedcentral.com)
- The concurrent inhibition of anti-apoptotic proteins and mTOR-mediated signaling in hypoxic KRAS/PIK3CA -mutant CRC cell lines resulted in pro-survival responses in parallel with the intended anti-proliferative effects, a finding that should be of note if considering combinatory targeting of multiple pathways in this CRC entity. (biomedcentral.com)
- These proteins regulate this fundamental biological process via the formation of heterodimers involving both pro- and anti-apoptotic family members. (inserm.fr)
- Disruption of the balance between anti- and pro-apoptotic Bcl-2 proteins is the cause of numerous pathologies. (inserm.fr)
- Bcl-xl, an anti-apoptotic protein of this family, is known to form heterodimers with multiple pro-apoptotic proteins, such as Bad, Bim, Bak, and Bid. (inserm.fr)
- 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)
- 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)
- The results identified amino acids of both the anti-apoptotic proteins as well as the Bcl-2 homology 3 (BH3) domains of the pro-apoptotic proteins that make strong, recurrent interactions in the protein complexes. (inserm.fr)
- The calculations show that the two anti-apoptotic proteins, Bcl-xl and Bcl-w, share a similar recognition mechanism. (inserm.fr)
- Forms homodimers, and heterodimers with BAX , BAD , BAK and Bcl-X(L). Heterodimerization with BAX requires intact BH1 and BH2 motifs, and is necessary for anti-apoptotic activity (By similarity). (sdsc.edu)
- Activation of downstream caspases through several stimuli leads to cleavage of target proteins and execution of the apoptotic program ( 13 ). (pnas.org)
- The cleaved protein, lacking the BH4 motif, has pro-apoptotic activity. (abcam.com)
- The BAD protein is a pro-apoptotic member of the Bcl-2 family whose ability to heterodimerize with survival proteins such as Bcl-X(L) and to promote cell death is inhibited by phosphorylation. (elsevier.com)
- The BAD protein derived from 11 of 41 tumor lines that expressed this pro-apoptotic protein migrated in gels as a clear doublet, consistent with the presence of hyperphosphorylated BAD protein. (elsevier.com)
- Taken together, these findings define for the first time the normal cell-type-specific patterns of expression and intracellular locations of the BAD protein in vivo and provide insights into the regulation of this pro-apoptotic Bcl-2 family protein in human tumors. (elsevier.com)
- Reed, John C. / Expression and location of pro-apoptotic bcl-2 family protein BAD in normal human tissues and tumor cell lines . (elsevier.com)
- The molecular interaction between tumor suppressor p53 and the anti-apoptotic Bcl-2 family proteins plays an essential role in the transcription-independent apoptotic pathway of p53. (ntu.edu.sg)
- In this study, we investigated the binding of p53 DNA-binding domain (p53DBD) with the anti-apoptotic Bcl-2 family proteins, Bcl-w, Mcl-1, and Bcl-2, using GST pull-down assay and NMR spectroscopy. (ntu.edu.sg)
- Noticeably, the refined structural models of the complexes between p53DBD and Bcl-w, Mcl-1, and Bcl-2 showed that the binding mode of p53DBD is highly conserved among the anti-apoptotic Bcl-2 family proteins. (ntu.edu.sg)
- Due to the myriad interactions between prosurvival and proapoptotic members of the Bcl-2 family of proteins, establishing the mechanisms that regulate the intrinsic apoptotic pathway has proven challenging. (rcsb.org)
- Using this mutant, we investigated the requirement for physical restraint of Bak by Bcl-xL in apoptotic regulation. (rcsb.org)
- Overexpression of the anti-apoptotic protein Bcl-2 attenuates neurodegeneration and delays activation of the caspases and fragmentation of β-actin. (jneurosci.org)
- In the present study, we demonstrate (1) that caspase-1 and caspase-3 are activated sequentially in the spinal cords of affected transgenic mSOD1 mice, (2) that activated caspase-3 is localized within neurons of the anterior horn that exhibit apoptotic features, and (3) that overexpression of Bcl-2 delays caspase activation in these animals. (jneurosci.org)
- This review will therefore discuss current opinions on how the Bcl-2 protein family couples the molecular events initiated by ER stress to the mitochondrial apoptotic pathway, their function on ER-mitochondrial Ca 2+ signaling, the unfolded protein response (UPR), and autophagy. (physiology.org)
- The intrinsic apoptotic response is mediated through phosphorylation of Bcl-2, which occurs rapidly after treatment with mebendazole in melanoma cells but not in melanocytes. (aacrjournals.org)
- A pro-apoptotic protein and member of the Bcl-2 protein family that is regulated by PHOSPHORYLATION. (uchicago.edu)
- These events were accompanied by increased gene expression of anti-apoptotic Bcl-2 and Bcl-XL, decreased expression of pro-apoptotic Bax and diminished caspase-3, −8 and −9 proteolytic activities. (springermedizin.de)
- Furthermore, inhibition of Bcl-2 anti-apoptotic family proteins with small molecules antagonists decreases protective effects of FAM3B in DU145 cells. (springermedizin.de)
- Furthermore, immunoprecipitation experiments showed that PHD3 upregulation reduced the formation of the Bax-Bcl-2 complex, inhibiting the anti-apoptotic effect of Bcl-2. (biomedsearch.com)
- This family of opposing cell survival and cell death proteins regulates pathways associated with apoptotic and non-apoptotic forms of cell death, as well as cellular macroautophagy - all of which are critical for both normal development and various pathologies, including many forms of cancer. (mcgill.ca)
- The first group contains anti-apoptotic members that possess all four BH domains and includes Bcl-2, Bcl-x L , Bcl-w, Mcl-1, Bcl-B, and A1. (hindawi.com)
- Anti-apoptotic Bcl-x L and Bcl-2 possess a hydrophobic cleft, the BH-3 binding groove, which can accommodate BH3-only members of proapoptotic proteins and neutralize their function [ 2 , 3 ]. (hindawi.com)
- The anti-apoptotic Bcl-2 and Bcl-xL proteins inhibit cytochrome c release through the mitochondrial pore and also inhibit activation of the cytoplasmic caspase cascade by cytochrome c. (wikipedia.org)
- J. Reed, C. Stein, S. Haldar, C. Subasinghe, C. Croce, S. Yum and J. Cohen, Antisense-mediated inhibition of Bcl-2 proto-oncogene expression and leukemic cell growth: Comparisons of phosphodiester and phosphorothioate oligodeoxynucleotides, Cancer Res . (springer.com)
- Whereas an inactive form of PKC-θ or knockdown of endogenous PKC-θ led to inhibition of Bcl-x L reporter. (jimmunol.org)
- The interpretation of this finding was the observed accumulation of APP and tau resulted from an inhibition in caspasemediated proteolysis following overexpression of Bcl-2. (pubmedcentralcanada.ca)
- This report reviews the recent progress of structures, functions and inhibition of Bcl-2 family proteins, especially the development of Bcl-2 inhibitors in past decades as anticancer agents. (eurekaselect.com)
- Guizhi Xiao, Hao Fang, Chengguo Xing and Wenfang Xu, " Structure, Function and Inhibition of Bcl-2 Family Proteins: A New Target for Anti-Tumor Agents", Mini-Reviews in Medicinal Chemistry (2009) 9: 1596. (eurekaselect.com)
- Down-regulation of Bcl-x L expression via inhibition of NF-κB activity correlated with chemosensitivity. (jimmunol.org)
- Additional analyses revealed that down-regulation of Bcl-x L /Bcl-2 by rituximab is a result of rituximab-mediated inhibition of the p38 MAPK, NF-κB ( 8 ), and ERK1/2 signaling pathways ( 10 ). (jimmunol.org)
- BAX is a member of the Bcl-2 gene family. (wikipedia.org)
- See the other reference sequence protein isoform for the Bcl2l14 gene (NP_001342615.1). (nih.gov)
- 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)
- 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)
- May specifically inhibit gene expression when recruited to promoter regions by sequence-specific DNA-binding proteins such as BCL6 and MLLT3. (uniprot.org)
- Bcl-2 is a member of a large gene family encoding proteins that can either inhibit (e.g. (sigmaaldrich.com)
- Protein encoded by the bcl-1 Gene which plays a critical Role in regulating the Cell Cycle . (online-medical-dictionary.org)
- Recent studies demonstrated that another C. elegans gene, ced-4, or its mammalian homolog Apaf-1 can bridge between Bcl-2/ced-9 family members and caspases ( 7 , 8 ). (pnas.org)
- Y. Tsujimoto, J. Cossman, E. Jaffe and C. Croce, Involvement of the Bcl-2 gene in human follicular lymphoma, Science 228: 1440 (1985). (springer.com)
- The bcl-2 gene was identified at chromosomal translocation breakpoints in follicular lymphomas and contributes to tumorigenesis by inhibiting programmed cell death rather than by stimulating cell growth ( 1 , 59 ). (asm.org)
- Furthermore, ectopic expression of PKC-θ stimulated a reporter gene driven by a mouse Bcl-x L promoter. (jimmunol.org)
- Furthermore, functional NF-κB binding sites were identified on the promoter region of Bcl-x L gene ( 10 , 11 ). (jimmunol.org)
- The mcl-1 gene encodes a 37-kDa protein with significant homology to Bcl-2, particularly in the carboxyl portion. (scielo.br)
- Below are the list of possible Bcl-2-like gene 16 protein products. (mybiosource.com)
- Characterization of a Herpes Simplex Virus 1 (HSV-1) Chimera in Which the Us3 Protein Kinase Gene Is Replaced with the HSV-2 Us3 Gene. (semanticscholar.org)
- The protein encoded by this gene belongs to the BCL2 protein family. (nih.gov)
- Overexpression of bcl-2 proteins, due to a translocation of the gene, is associated with follicular lymphoma. (rush.edu)
- Overexpression of Cyclin D1 is the result of bcl-1 rearrangement, a t(11;14) translocation, and is implicated in various Neoplasms . (online-medical-dictionary.org)
- In recent years, a rising number of biological dysfunctions involved in SCLC pathogenesis were reported, including ectopic expression of neuroendocrine regulatory peptides, overexpression of Myc family oncogenes and extracellular matrix proteins, as well genetic abnormalities in the tumor suppressor genes p53 and pRB ( 1 , 2 ). (aacrjournals.org)
- Overexpression of Bcl-2 prevented caspase activation, the caspase cleavage of tau and improved place recognition memory in 3xTg-AD mice [ 8 ]. (pubmedcentralcanada.ca)
- An additional finding of that study was the accumulation of full-length APP and tau following overexpression of Bcl-2 in 3xTg-AD mice [ 8 ]. (pubmedcentralcanada.ca)
- However, direct demonstration that APP is cleaved by caspases and is prevented following overexpression of Bcl-2 was not investigated. (pubmedcentralcanada.ca)
- 6 ], we now demonstrate caspase-cleavage of APP does occur in 3xTgAD mice and is prevented along with the formation of extracellular deposits of Aβ following overexpression of Bcl-2. (pubmedcentralcanada.ca)
- Overexpression of Bcl-2 contributes to resistance of cancer cells to human cytotoxic lymphocytes (CL) by blocking granzyme B (GraB)-induced mitochondrial outer membrane permeabilization (MOMP). (isharonline.org)
- In nonapoptotic cells the proapoptotic BCL-2 proteins BAX and BAK but also prosurvival family members, like BCL-x L or MCL-1, translocate to the outer mitochondrial membrane (OMM) and retrotranslocate from the mitochondria back into the cytosol. (springer.com)
- 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)
- 17 Some members of the Bcl-2 protein family when bound to the mitochondria regulate the function of the large polymeric channel, permeability transition pore complex, 18 located at the point of contact between the inner and the outer mitochondrial membranes. (bmj.com)
- In many types of normal cells, BAD immunoreactivity was associated with cytosolic organelles resembling mitochondria, suggesting that BAD is often heterodimerized with other Bcl-2 family proteins in vivo. (elsevier.com)
- He then looks at the molecular machinery that links signals that cause cell death to caspases, emphasizing the importance of the BCL-2 family of proteins and the role of cytochrome c released from mitochondria. (cshlpress.org)
- Caspase-2 failed to induce cytochrome c release from mitochondria with Bid -/- background, and the release could be restored by addition of the wild-type Bid protein, but not by Bid with the caspase-2 cleavage site mutated. (elsevier.com)
- Here, we show that wild-type Bcl-2 antiapoptotic proteins, but not Beclin 1 binding defective mutants of Bcl-2, inhibit Beclin 1-dependent autophagy in yeast and mammalian cells and that cardiac Bcl-2 transgenic expression inhibits autophagy in mouse heart muscle. (nih.gov)
- Forced expression of Bcl-2 in cardiac muscle of transgenic mice decreased the number of autophagic structures that appeared in mice after 48 hours of starvation. (sciencemag.org)
- In MCF7 cells (which do not have wild-type beclin 1), expression of mutant forms of beclin 1 that could not bind Bcl-2 caused an increase in basal, as well as starvation-induced, autophagic structures. (sciencemag.org)
- 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)
- Because DLCL derive from germinal-center B cells, deregulated BCL-6 expression may contribute to lymphomagenesis by preventing postgerminal center differentiation. (uniprot.org)
- Following treatment with sirtinol (inhibitor of SIRT1), the expression of the pro-survival protein Bcl-2 was markedly decreased in both MCF-7 and MDA-MB-231 cell lines, particularly in MDA-MB-231. (nih.gov)
- This was seen from increased intensity of immunohistochemical staining for Bad protein against the background of more pronounced expression of Bcl-2 protein. (springer.com)
- Is the Subject Area "Protein expression" applicable to this article? (plos.org)
- The expression of caspase‑3, Bax and Bcl‑2 genes was detected by the reverse transcriptase polymerase chain reaction (RT‑PCR). (spandidos-publications.com)
- Recently, we found increased bcl-2 expression in cervical carcinoma cell lines containing mutated or E6-inactivated p53 (X. L. Liang, S. Mungal, A. Ayscue, J. D. Meissner, P. Wodnicki, G. Gordon, S. Lockett, and B. Herman. (aacrjournals.org)
- Here, we compared the relative expression of BH3-only proteins in the spinal cord of end-stage G93A mutant SOD1 mice to age-matched wild-type (WT) mice. (frontiersin.org)
- Finally, examination of protein expression using western blotting also revealed marked increases in DP5/Hrk and BNip3L in G93A mutant SOD1 lumbar spinal cord lysates compared to WT controls. (frontiersin.org)
- Therefore, the current model is that PI3K/Akt pathway-mediated activation of NF-κB is responsible for stimulating Bcl-x L expression, resulting in enhanced survival of T cells. (jimmunol.org)
- The expression of P53, Bcl-2, Bax, Bag-1, and Mcl-1 proteins in CD5/CD20-positive B-chronic lymphocytic leukemia (B-CLL) cells from 30 typical CLL patients was evaluated before and after 48 h of incubation with 10 -6 M fludarabine using multiparametric flow cytometric analysis. (scielo.br)
- Protein expression was correlated with annexin V expression, Rai modified clinical staging, lymphocyte doubling time, and previous treatment. (scielo.br)
- B) BCL-2 expression levels in Jurkat and WEHI-231 clones, determined by Western blot analysis of lysates from equivalent cells of various Jurkat or WEHI-231 clones with anti-hBCL-2 Ab 6C8 and anti-β-actin Ab. (asm.org)
- Intriguingly, we observed low Bcl-2 family proteins levels in the SCLC cells with a constitutive Akt pathway activation, whereas an increased expression was detected in the RAD001-resistant SCLC cells. (aacrjournals.org)
- Importantly, the differences in SCLC cells' responsiveness to RAD001 are based on the activation status of the Akt/mTOR pathway and the expression levels of Bcl-2 family proteins. (aacrjournals.org)
- Based on our findings, for a clinical relevant application it may be of advantage to screen SCLC patients for Akt/mTOR pathway activation status and Bcl-2 family expression prior to considering the use of RAD001 in combination with chemotherapeutic agents such as etoposide. (aacrjournals.org)
- Expression profiles of p53, p21, bax and bcl-2 proteins in all-trans-retinoic acid treated primary and metastatic melanoma cells. (diva-portal.org)
- The protein expression of p53, p21, bax and bcl-2 were examined by Western blotting and immunocytochemistry. (diva-portal.org)
- Expression of p53, p21 and bax was increased, and bcl-2 was decreased in melanoma cells after exposure to atRA at different concentrations for various periods of time. (diva-portal.org)
- we investigated the expression of molecules involved in muscle fibre death and survival mechanisms (Bcl-2, Fas, Fas-ligand and TRAIL), focusing on disorders with possible involvement of cytotoxic T cells. (diva-portal.org)
- By using immunohistochemistry, Western blot and real-time PCR we detected a constitutional expression of Bcl-2 in healthy muscle, whereas the expression was weaker in disease processes. (diva-portal.org)
- Methods -The expression of Bcl-2, Bcl-X L , and Mcl-1 was investigated in normal biliary epithelium (17), biliary dysplasia (three), and invasive cholangiocarcinoma (51), in addition to three human cholangiocarcinoma cell lines, by immunohistochemistry and immunofluorescence. (bmj.com)
- Results -The expression of Bcl-2 was not detected in normal or malignant biliary tissue. (bmj.com)
- 22- 24 Studies involving a variety of haematological and several solid malignancies have identified a correlation between high Bcl-2 or Bcl-X L expression, poor patient response to treatment, and overall prognosis. (bmj.com)
- The expression of caspases and members of the Bcl-2 family was examined through immunoblot analysis. (springermedizin.de)
- Expression of Bcl-2 family proteins and associated clinicopathologic factors predict survival outcome in patients with oral squamous cell carcinoma. (semanticscholar.org)
- Immunohistochemistry was used to evaluate protein expression in 53 primary OSCCs treated by radical surgery with free margins at a single institution in 1999. (semanticscholar.org)
- Expression of Bcl-X L inhibited the association of Apaf-1 with caspase-9 in mammalian cells. (pnas.org)
- Bcl-2 expression was as follows: chronic gastritis 0%, atrophic gastritis 35% (23/65 cases), intestinal metaplasia 90% (45/50 cases), dysplasia 100% (40/40 cases), intestinal type adenocarcinoma 83.3% (25/30 cases), and diffuse type adenocarcinoma 70% (14/20 cases). (openarchives.gr)
- In 10 matched-pair cell lines [established at diagnosis (DX) and progressive disease (PD) from the same patients], BCL-2 expression in the DX and PD lines was comparable, suggesting that BCL-2 expression at diagnosis may provide a biomarker for neuroblastomas likely to respond to 4-HPR + ABT-199. (aacrjournals.org)
- Monoclonal antibodies were generated against the human BAD protein and used to evaluate its expression by immunoblotting and immunohistochemistry in normal human tissues and by immunoblot analysis of the National Cancer Institute anti-cancer drug screening panel of 60 human tumor cell lines. (elsevier.com)
- Immunostaining of tissues revealed many examples of cell-type-specific expression of BAD, suggesting dynamic regulation of BAD protein levels in vivo. (elsevier.com)
- The relative levels of BAD protein varied widely among established human tumor cell lines, with colon, lung, and melanomas generally having the highest expression. (elsevier.com)
- The regulation of chemoresistance by NF-κB is mediated via Bcl-x L expression, whereas the regulation of Fas resistance by NF-κB is mediated via YY1 expression and activity. (jimmunol.org)
- The Bcl-xL (54H6) Rabbit mAb confirms silencing of Bcl-xL expression, while the α-Tubulin (11H10) Rabbit mAb is used as a loading control. (cellsignal.com)
- The p53 NTD/ Bcl-XL complex was observed and obtained in a co-expression system in E.coli. (ntu.edu.sg)
- CD44 and Bcl-2 expression was detected in 86% and 82% of breast tumours, respectively. (aacrjournals.org)
- There was no significant correlation between CD44+ tumour cell prevalence and tumour characteristics, whereas the prevalence of CD44+ cells was associated with higher levels of Bcl-2 expression ( P = 0.004). (aacrjournals.org)
- Our findings suggest that the prevalence of CD44+ tumour cells as a subpopulation of breast cancer stem cells was of no clinicopathological significance, but was correlated with higher Bcl-2 expression. (aacrjournals.org)
- The resistance of CSCs to chemotherapy may be caused through increased expression of the Bcl-2 family proteins, which leads to increased expression of membrane proteins responsible for drug resistance. (aacrjournals.org)
- The expression of 5-lipoxygenase activating protein (FLAP) in murine hematopoietic FL5.12 cells that are transfected to overexpress bcl-x L is less than in control cells. (elsevier.com)
- Consistent with this notion are reports of modified expression of proapoptotic and antiapoptotic factors such as Bcl-2, Bcl-XL, and Mcl-1 in melanoma ( 3 , 4 ). (aacrjournals.org)
- However, studies regarding the expression of these proteins in colorectal adenomaadenocarcinoma transformation sequence are yet to be described. (omicsonline.org)
- In this study, we examined the expression patterns of Beclin-1, Bcl-2 and p 62 in both colorectal adenomas and adenocarcinomas. (omicsonline.org)
- Cytoplasmic Bcl-2 expression was moderately expressed in tubular adenomas but negative to low expression was observed in the adenocarcinomas. (omicsonline.org)
- In T cells, Bcl-2 expression is relatively consistent, whereas Bcl-x L expression is induced in response to environment stimuli. (hindawi.com)
- In this paper, we will focus on the function and regulation of expression of Bcl-x L in developing and activated mature T cells. (hindawi.com)
- 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)
- BCL-2 , the first family member, forms the molecular basis for sustaining the lymphoma cancer cells. (britannica.com)
- The interaction between beclin 1 and Bcl-2 was confirmed in HT-29 cells overexpressing Bcl-2 by coimmmunoprecipitation, and beclin 1 was identified on endoplasmic and mitochondrial membranes (the locations of Bcl-2) based on cell fractionation and confocal microscopy. (sciencemag.org)
- In HT-29 cells overexpressing Bcl-2, the formation of the beclin and hVps34 complex, which has class III phosphoinositide 3-kinase (PI3K) activity, was inhibited, as was the colocalization of beclin 1 with PI3P (phosphatidylinositol 3-phosphate), suggesting that Bcl-2 inhibited the PI3K activity of the beclin 1-hVSP34 complex. (sciencemag.org)
- In HeLa cells, which endogenously express both beclin 1 and Bcl-2, Bcl-2 and beclin 1 coimmunoprecipitated under nutrient-rich conditions, and this interaction was decreased when the cells were starved of nutrients. (sciencemag.org)
- Knockdown of Bcl-2 in HeLa cells with siRNA resulted in an increase in the number of autophagic structures under starvation conditions compared with those observed in starved cells with wild-type levels of Bcl-2. (sciencemag.org)
- The retrotranslocation of BCL-2 proteins from the OMM can be measured using fluorescence-labeled protein in intact cells or endogenous protein from isolated heavy membrane fractions. (springer.com)
- BCL-6 protein is expressed in germinal-center B cells. (uniprot.org)
- Western blot analysis of human tumor cell lines representative of various hematopoietic lineages/stages of differentiation showed that the BCL-6 protein is predominantly expressed in the B-cell lineage where it was found in mature B cells. (uniprot.org)
- The BCL-6 protein was also detectable in inter- and intra-follicular CD4+ T cells, but not in other follicular components including mantle-zone B cells, plasma cells, dendritic cells, and macrophages. (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)
- Interactions of endogenous proteins p53 and p21 in IMR-32 neuroblastoma and H460 lung cancer cells. (aacrjournals.org)
- A major mechanism by which mammalian cells kill themselves involves members of the BCL‐2 family of proteins, some of which promote cell death, and others which inhibit cell death. (els.net)
- Interaction of overexpressed p53 and p21 proteins in p53-null H1299 cells correlated with decreased cell invasion. (aacrjournals.org)
- Deletion of the BH1, BH2, or BH4 domains of Bcl-2 abolishes its ability to suppress cell death in mammalian cells and prevents homodimerization of these mutant proteins, though these mutants can still bind to the wild-type Bcl-2 protein. (springer.com)
- KSBcl-2, encoded by the Kaposi's sarcoma-associated herpesvirus, was the only viral Bcl-2 homolog that was capable of killing cells when expressed as an N-terminal truncation. (asm.org)
- Thus, the PKC-θ-mediated signals may function not only in the initial activation of naive CD4 + T cells, but also in their survival during T cell activation by regulating Bcl-x L levels through NF-κB and AP-1 pathways. (jimmunol.org)
- Both thymocytes and T cells overexpressing gag-PKB displayed elevated levels of the antiapoptotic molecule Bcl-X L . In addition, the activation of peripheral T cells led to enhanced nuclear factor (NF)-κB activation via accelerated degradation of the NF-κB inhibitory protein IκBα. (rupress.org)
- Our data highlight a physiological role for PKB in promoting survival of DP thymocytes and mature T cells, and provide evidence for the direct association of three major survival molecules (PKB, Bcl-X L , and NF-κB) in vivo in T lymphocytes. (rupress.org)
- Our main goal was to determine the predictive value of these proteins in CLL cells in terms of disease evolution. (scielo.br)
- At least 15 Bcl-2 family members have been identified in mammalian cells and several others in viruses. (acris-antibodies.com)
- BCL-2 was immunoprecipitated from 32 P-orthophosphate-labeled Jurkat-BCL-2 cells treated with paclitaxel (+) or DMSO (−) by using anti-hBCL-2 Ab 6C8, separated by SDS-PAGE, and transferred to a nitrocellulose membrane. (asm.org)
- Immunoprecipitated BCL-2 from Jurkat-BCL-2 cells treated with paclitaxel was incubated with λPPase at 30°C for 30 min with or without phosphatase inhibitors (50 mM NaF, 2 mM sodium orthovanadate, 5 mM EDTA, and 5 mM EGTA). (asm.org)
- An antisense construct targeting Bcl-2 or a Bcl-2-specific inhibitor was able to sensitize resistant SCLC cells to RAD001. (aacrjournals.org)
- Furthermore, it has been found that the ribosomal protein S6 kinases-1 and -2 (S6K1, 2) are highly overexpressed in SCLC cells compared with normal human type II pneumocytes, and that mTOR transduces mitogen-induced proliferation in SCLC ( 6 ). (aacrjournals.org)
- Modification of these protein levels in the tumour cells might be beneficial for early treatment of melanoma. (diva-portal.org)
- In contrast, granular cytoplasmic Bcl-X L and Mcl-1 staining was found in 60-100% of cells in all normal, dysplastic, and malignant specimens, including the human cell lines examined in this study. (bmj.com)
- Conclusion -These findings indicate that Mcl-1 and Bcl-X L , but not Bcl-2, are involved in the survival of normal and neoplastic cells in the biliary tree. (bmj.com)
- Conformational changes in inhibitory PAS domain protein associated with binding of HIF-1α and Bcl-xL in living cells. (nii.ac.jp)
- Finally, the viability of cancer cells transfected with a plasmid containing HBx (hepatitis B virus X protein) following treatment with TRAIL was also measured. (springermedizin.de)
- Bcl-X L , an antiapoptotic member of the Bcl-2 family, was shown to physically interact with Apaf-1 and caspase-9 in mammalian cells. (pnas.org)
- Significantly, recombinant Bcl-X L purified from Escherichia coli or insect cells inhibited Apaf-1-dependent processing of caspase-9. (pnas.org)
- Bcl-X(S) is expressed at high levels in cells that undergo a high rate of turnover, such as developing lymphocytes. (abcam.com)
- In contrast, Bcl-X(L) is found in tissues containing long-lived postmitotic cells, such as adult brain. (abcam.com)
- Western blot analysis of extracts from Jurkat and HeLa (human), COS (monkey), NIH/3T3 and L929 (mouse), and PC12 and C6 (rat) cells, using Bcl-xL (54H6) Rabbit mAb. (cellsignal.com)
- Western blot analysis of extracts from HeLa cells, transfected with 100 nM SignalSilence ® Control siRNA (Unconjugated) #6568 (-), SignalSilence ® BcL-xL siRNA I (+) or SignalSilence ® Bcl-xL siRNA II #6363 (+), using Bcl-xL (54H6) Rabbit mAb #2764 (upper) or α-Tubulin (11H10) Rabbit mAb #2125 (lower). (cellsignal.com)
- Confocal immunofluorescent analysis of HeLa cells using Bcl-xL (54H6) Rabbit mAb (green). (cellsignal.com)
- Flow cytometric analysis of untreated Jurkat cells, using Bcl-xL (54H6) Rabbit mAb (blue) compared to a nonspecific negative control antibody (red). (cellsignal.com)
- Western blot analysis of extracts from Jurkat cells, untreated or treated with paclitaxel (1 μM, overnight) and with or without λ phosphatase, using Phospho-Bcl-2 (Ser70) (5H2) Rabbit mAb (upper) or Bcl-2 #2876 (lower). (cellsignal.com)
- Flow cytometric analysis of Jurkat cells using Phospho-Bcl-2 (Ser70) (5H2) Rabbit mAb and Propidium Iodide (PI)/RNase Staining Solution #4087 to measure DNA content. (cellsignal.com)
- Western blot analysis of control HeLa cells (lane 1) or Bcl-2 knockout HeLa cells (lane 2) using Bcl-2 (D55G8) Rabbit mAb #4223 (upper), or β-actin (13E5) Rabbit mAb #4970 (lower). (cellsignal.com)
- The absence of signal in the Bcl-2 knockout HeLa cells confirms the specificity of the antibody for Bcl-2. (cellsignal.com)
- The method includes increasing the activity of Bcl-2 in cells affected by the disease or pathological condition. (google.com)
- The method includes increasing the activity of Bcl-2 in a population of cells and transplanting the population of cells having increased Bcl-2 activity into a subject. (google.com)
- A method to enhance the sensitivity of malignant cells to therapy is provided that includes decreasing the activity of Bcl-2 in the malignant cells. (google.com)
- 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)
- Basal FLAP mRNA levels were actually 2.8-fold higher in bcl-x L than control cells indicating that this difference does not have a transcription basis. (elsevier.com)
- In addition, an examination of FLAP mRNA levels in response to withdrawal of IL-3 revealed a 2-3-fold increase after 4 and 8 h relative to time-matched samples in both control and bcl-x L overexpressing cells. (elsevier.com)
- This further indicates that the decrease in FLAP levels in bcl-x L overexpressing cells is not related to transcription and suggests an attempt at compensation perhaps in response to increased FLAP degradation/turnover. (elsevier.com)
- A proteolytic mechanism was explored by examining the effect of the general caspase inhibitor Boc-D-FMK, and the non-caspase protease inhibitors phenylmethylsulfonyl fluoride (PMSF), pepstatin and leupeptin, on the loss of FLAP in bcl-x L overexpressing cells subsequent to IL-3 withdrawal. (elsevier.com)
- The functional consequences of a loss of FLAP in growth-factor deprived cells overexpressing bcl-x L is not known. (elsevier.com)
- Biswal, SS , Datta, K & Kehrer, JP 2001, ' Association between bcl-x L and 5-lipoxygenase activating protein (FLAP) levels in IL-3-dependent FL5.12 cells ', Toxicology , vol. 160, no. 1-3, pp. 97-103. (elsevier.com)
- Basal FLAP mRNA levels were actually 2.8-fold higher in bcl-xL than control cells indicating that this difference does not have a transcription basis. (elsevier.com)
- Our data provide evidence that the antineoplastic effects of mebendazole in human melanoma cells result from differential Bcl-2-mediated cellular responses to mebendazole-induced tubulin disruption. (aacrjournals.org)
- Autophagy, an integral part of cellular homeostasis, is essentially crucial in ensuring the survival of cells or organisms through recycling of unwanted proteins and/ or generation of energy for urgent need. (omicsonline.org)
- Culture growth and viability of DU145 cell line were evaluated after treatment with either exogenous FAM3B protein obtained from conditioned media (CM) of 293 T cells overexpressing FAM3B or a recombinant FAM3B protein produced in a bacterial host. (springermedizin.de)
- DU145 cells overexpressing FAM3B protein were produced by lentiviral-mediated transduction of full-length FAM3B cDNA. (springermedizin.de)
- Cholangiocarcinoma cells express high levels of the antiapoptotic proteins Bcl-X L and Mcl-1 and are markedly chemo- and radioresistant. (bmj.com)
- Consistent with this we found that ABT-737 effectively restored MOMP in Bcl-2 overexpressing cells treated with GraB or natural killer cells. (isharonline.org)
- In addition to its critical function in the thymus, Bcl-x L also regulates the survival of peripheral T cells. (hindawi.com)
- Activated T cells upregulate Bcl-x L to enhance their own survival. (hindawi.com)
- Therefore, Bcl-x L ensures the survival of both developing and peripheral T cells, which is essential for a functional immune system. (hindawi.com)
- Although they demonstrated si-p53 or si-p21 affect Bcl-w:Bax interaction, they did not prove endogenous p53 interacts with p21. (aacrjournals.org)
- Homodimerization of Bcl-2 with itself involves a head-to-tail interaction, in which an N-terminal domain where BH4 resides interacts with the more distal region of Bcl-2 where BH1, BH2, and BH3 are located. (springer.com)
- CED-4 interacts with CED-3 and CED-9 forming a multimeric protein complex ( 7 - 9 ). (pnas.org)
- This antiautophagy function of Bcl-2 may help maintain autophagy at levels that are compatible with cell survival, rather than cell death. (nih.gov)
- Those most similar to Bcl-2 promote cell survival by inhibiting adapters needed for activation of the proteases (caspases) that dismantle the cell. (sciencemag.org)
- Once activated, they were thought to bind promiscuously to pro-survival protein targets but unexpected selectivity has recently emerged from analysis of their interactions. (nih.gov)
- Whether Bax and Bak are activated directly by these BH3-only proteins, or indirectly as a consequence of BH3-only proteins neutralizing their pro-survival targets is the subject of intense debate. (nih.gov)
- Our hypothesis is that Bcl-2 pro-survival proteins provide a survival advantage for melanomas and might contribute to resistance to standard chemotherapeutic drugs. (edu.au)
- Our research aims to identify the key Bcl-2 pro-survival proteins that are responsible for melanoma survival. (edu.au)
- The second aim is to determine whether resistance to current melanoma treatment arises due to elevated levels of Bcl-2 pro-survival proteins, and whether treatment with Bcl-2-targeting molecules will resensitise tumours to standard drugs, informing potential drug treatment combinations. (edu.au)
- The Bcl-2 family of proteins is a major cell death regulator and is implicated in determining the survival or death of neurons under physiological as well as pathological conditions. (springer.com)
- In addition, TCR stimulation results in up-regulation of Bcl-x L to enhance T cell survival intrinsically. (jimmunol.org)
- Akt, a target of PI3K, has been shown to mediate T cell survival by regulating Bcl-x L most likely via activation of NF-κB ( 9 ). (jimmunol.org)
- The serine/threonine kinase protein kinase B (PKB)/Akt mediates cell survival in a variety of systems. (rupress.org)
- Bcl-2-related proteins function to promote either cell survival (such as Bcl-2 and Bcl-X L ) or cell death (such as Bax and BAD). (rupress.org)
- The serine/threonine kinase protein kinase Bα (PKB/Akt), a downstream target of PI3K activity, is emerging as a key molecule involved in regulating cell survival in a variety of models ( 16 ). (rupress.org)
- These "BH3 domain" proteins may well represent the physiological antagonists of the pro-survival proteins. (acris-antibodies.com)
- 4-HPR + ABT-199 was highly synergistic against high BCL-2-expressing neuroblastoma cell lines and significantly improved event-free survival of mice carrying high BCL-2-expressing patient-derived xenografts (PDX). (aacrjournals.org)
- His current research focuses on mitochondrial physiology in cell survival and cell death, the functions of the BCL-2 family, and other aspects of cell death. (cshlpress.org)
- In vivo, loss of Bcl-xL binding to Bak led to significant defects in T-cell and blood platelet survival. (rcsb.org)
- Manicassamy S, Yin D, Zhang Z, Molinero LL, Alegre ML, Sun Z. A critical role for protein kinase C-theta-mediated T cell survival in cardiac allograft rejection. (uchicago.edu)
- DU145 cell viability and survival increased after exogenous treatment with recombinant FAM3B protein or FAM3B-secreted protein. (springermedizin.de)
- To evaluated p53, cyclin D1 and Bcl-2 immunoexpressions in esophagogastric junction adenocarcinoma patients, without Barrett's esophagus, and to compared to clinicopathological characteristics and survival rate. (scielo.br)
- In this selected population, there was no association between the immunomarkers, p53, cyclin D1 and bcl-2 and clinicopathological data and/or overall survival. (scielo.br)
- Bcl-x L -mediated survival is required for the generation of effectors that carry out the actual immune responses. (hindawi.com)
- Thus, Bcl-2 not only functions as an antiapoptotic protein, but also as an antiautophagy protein via its inhibitory interaction with Beclin 1. (nih.gov)
- Using a yeast autophagy reconstitution assay and two transfected mammalian cell systems, Bcl-2 was found to inhibit beclin 1-mediated formation of autophagic structures through a mechanism that required the functional binding sites mediating the interaction between these two proteins. (sciencemag.org)
- No coimmunoprecipitation experiments documenting endogenous p53:p21 protein interaction were performed. (aacrjournals.org)
- A combination of the solution studies together with a new application of DCA to the eukaryotic proteins NAF-1 and Bcl-2 provided sufficient constraints at amino acid resolution to predict the interaction surfaces and orientation of the protein-protein interactions involved in the docked structure. (sigmaaldrich.com)
- In contrast, Bcl-2/Bax heterodimerization involves a tail-to-tail interaction, that requires the portion of Bcl-2 where BH1, BH2, and BH3 reside and a central region in Bax where the BH3 domain is located. (springer.com)
- 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)
- Here we describe a mutation in mouse and human Bak that specifically disrupts its interaction with the prosurvival protein Bcl-xL Substitution of Glu75 in mBak (hBAK Q77) for leucine does not affect the three-dimensional structure of Bak or killing activity but reduces its affinity for Bcl-xL via loss of a single hydrogen bond. (rcsb.org)
- Bcl-2-related proteins act upstream from caspases in the cell death pathway ( 6 ). (pnas.org)
- Initiators such as caspase-8 and caspase-9 are apical caspases that are activated on binding to specialized molecular platforms that are assembled through selective protein-protein interactions. (aacrjournals.org)
- To determine if viral Bcl-2 proteins can be converted into death factors, similar to their cellular counterparts, five herpesvirus Bcl-2 homologs from five different viruses were tested for their susceptibility to caspases. (asm.org)
- Thus, herpesvirus Bcl-2 homologs escape negative regulation by retaining their antiapoptotic activities and/or failing to be converted into proapoptotic proteins by caspases during programmed cell death. (asm.org)
- The function of cellular Bcl-2 family members is regulated in part by caspases. (asm.org)
- They become activated through proteolysis by already active caspases or through autocatalytic processing, which is mediated by aggregation of zymogens in a complex containing adapter proteins (e.g. (biologists.org)
- This protein is reported to interact with, and increase the opening of, the mitochondrial voltage-dependent anion channel (VDAC), which leads to the loss in membrane potential and the release of cytochrome c. (wikipedia.org)
- Shimizu, S., Narita, M. and Tsujimoto T, Y Bcl-2 family proteins regulate the release of apoptogenic cytochrome c by the mitochondrial channel VDAC. (springer.com)
- Permeabilization of the mitochondrial outer membrane (MOM) and the consequent release of cytochrome c is regulated by a group of proteins known as the B-cell lymphoma protein 2 (Bcl-2) protein family. (physiology.org)
- now show that Bcl-2 also inhibits autophagy through its interactions with beclin 1. (sciencemag.org)
- Regardless of this, a detailed understanding of the interactions between family members, which are often selective, has notable implications for designing anti-cancer drugs to target the Bcl-2 family. (nih.gov)
- To gain better understanding of how this protein functions, we have undertaken a structure-function analysis of this protein, focusing on domains within Bcl-2 that are required for function and for interactions with other proteins. (springer.com)
- The molecular platforms in charge of initiator caspase activation are formed through interactions involving distinct protein folds or binding cassettes, of which three have been structurally characterized: death domains, death effector domains, and caspase recruitment domains ( 13 ). (aacrjournals.org)
- A) Interactions between Bcl-2 family members show the rationale of our experiments. (rupress.org)
- Molecular basis for Bcl-2 homology 3 domain recognition in the Bcl-2 protein family: identification of conserved hot spot interactions. (inserm.fr)
Mitochondrial outer membrane1
- Although BAX and BAK can spontaneously activate to allow mitochondrial membrane permeability, this might be accelerated by the presence of certain BH3‐only proteins on the mitochondrial outer membrane. (els.net)
- PI3K-mediated phosphorylation of phosphatidylinositol functions to recruit PKB and the protein kinases PDK-1 and PDK-2 to the plasma membrane, allowing for direct phosphorylation of PKB by these kinases. (rupress.org)
- PKB has been shown to antagonize the proapoptotic functions of the Bcl-2-related molecule BAD ( 19 )( 20 ) and caspase 9 ( 21 ) through direct phosphorylation. (rupress.org)
- A) The mobility shift of BCL-2 induced by paclitaxel is due to phosphorylation. (asm.org)
- Paclitaxel induces phosphorylation of Ser70, Ser87, and Thr69 in BCL-2 (A) 2D mapping and synthetic phosphopeptide comigration study of band 1. (asm.org)
- Substitution of phosphorylation sites in BCL-2 further enhances antiapoptotic activity. (asm.org)
- A) Jurkat clones and WEHI-231 clones stably expressing WT or alanine-substituted phosphorylation sites of BCL-2, consisting of Ser70 (S70A), Ser87 (S87A), or all three phosphorylation sites, including Thr69 plus the two serines (AA/A), or an empty vector (Neo) were generated. (asm.org)
- An important protein, Beclin 1, which complexes with Vps34, is recruited at the site of autophagosome formation through phosphorylation of Ambral [ 3 ]. (omicsonline.org)
- This nuclear function of p53 is distinguished from the function of cytoplasmic p53, which suppresses cell invasion by liberating Bax from prosurvival Bcl-2 proteins ( 6 ). (aacrjournals.org)
- It was reported that distinct motifs within the cytoplasmic domain of CD28 regulate T cell proliferation and induction of Bcl-x L ( 7 ), suggesting differential signals are responsible for these two CD28-regulated biological effects. (jimmunol.org)
- Immunohistochemical analysis of paraffin-embedded human prostate carcinoma, showing cytoplasmic localization, using Bcl-xL (54H6) Rabbit mAb. (cellsignal.com)
- Conditions that disrupt the luminal environment and these core ER functions, including oxidative stress, perturbation of Ca 2+ or energy stores and accumulation of unfolded/misfolded proteins result in an evolutionarily conserved adaptive response termed the UPR. (nature.com)
- These experiments demonstrate that Bcl-X L associates with caspase-9 and Apaf-1, and show that Bcl-X L inhibits the maturation of caspase-9 mediated by Apaf-1, a process that is evolutionarily conserved from nematodes to humans. (pnas.org)
Prosurvival Bcl-2 family3
- The indirect activation model suggests that they simply must neutralize all of the prosurvival Bcl-2 family members, whereas the direct activation model proposes that Bim and Bid must activate Bax and Bak directly. (rupress.org)
- In this model, the prosurvival Bcl-2 family members hold subpopulations of Bax and Bak molecules in check until BH3-only proteins free them. (rupress.org)
- The preclinical and clinical properties of the small molecules inhibiting prosurvival BCL-2 family proteins have been extensively reviewed [5-16]. (immune-source.com)
Motifs known as Bcl-2 homology2
- Several isoforms of BCL2-associated X protein occur due to ALTERNATIVE SPLICING of the mRNA for this protein. (harvard.edu)
- Lauterwasser J., Fimm-Todt F., Edlich F. (2019) Assessment of Dynamic BCL-2 Protein Shuttling Between Outer Mitochondrial Membrane and Cytosol. (springer.com)
- Antiapoptotic members of the Bcl-2 protein family localise to the outer mitochondrial membrane and regulate mitochondrial release of apoptogenic proteins. (bmj.com)
- It does not contain a C-terminal transmembrane domain for outer mitochondrial membrane and nuclear envelope targeting, unlike most other members of the Bcl-2 family. (wikipedia.org)
- Subsequent studies identified a family of Bcl-2-related proteins possessing several conserved Bcl-2 homology (BH) domains important for homo- or heterodimerization between family members ( 11 - 13 ). (pnas.org)
- The BH1 and BH2 motifs are required for both heterodimerization with other Bcl-2 family members and for repression of cell death. (abcam.com)
- Thus, Bcl-2 appears to be a more general inhibitor of cell death than previously appreciated. (sciencemag.org)
- PI3K is required for CD28-mediated induction of Bcl-x L , as up-regulation of Bcl-x L is prevented by a pharmacological inhibitor of PI3K, and by mutation of the CD28 residues essential for PI3K activation ( 7 , 8 ). (jimmunol.org)
- The present article updates the small molecules targeting proteins of the BCL-2 family with the discovery of not only highly potent antagonists of prosurvival members but also direct activators of the MOMP effectors BAX and BAK and a dual prosurvival inhibitor/proapoptotic activator. (immune-source.com)
- Interestingly, sabutoclax has turned out to be a pan-BCL-2 inhibitor in some but not all cellular systems, displaying its best activity in inhibiting MCL-1 . (immune-source.com)
- Fenretinide (4-HPR) is a cytotoxic retinoid with clinical activity in recurrent neuroblastoma and venetoclax (ABT-199) is a selective inhibitor of the antiapoptotic protein B-cell lymphoma-2 (BCL-2). (aacrjournals.org)
- A member of the Bcl-2 protein family and homologous partner of C-BCL-2 PROTO-ONCOGENE PROTEIN. (harvard.edu)
- The cardinal member of this family, BCL-2, was originally discovered as the defining oncogene in follicular lymphomas, located at one reciprocal breakpoint of the t(14;18) (q32;q21) chromosomal translocation. (aacrjournals.org)
- Additionally, the report provides an overview of key players involved in G1/S Specific Cyclin D1 (B Cell Lymphoma 1 Protein or BCL 1 Oncogene or PRAD1 Oncogene or CCND1) targeted therapeutics development and features dormant and discontinued projects. (globalmarketsdirect.com)
- The report analyses the pipeline products across relevant therapy areas under development targeting G1/S Specific Cyclin D1 (B Cell Lymphoma 1 Protein or BCL 1 Oncogene or PRAD1 Oncogene or CCND1). (globalmarketsdirect.com)
- The report provides a snapshot of the Global therapeutic landscape for G1/S Specific Cyclin D1 (B Cell Lymphoma 1 Protein or BCL 1 Oncogene or PRAD1 Oncogene or CCND1). (globalmarketsdirect.com)
- The report reviews G1/S Specific Cyclin D1 (B Cell Lymphoma 1 Protein or BCL 1 Oncogene or PRAD1 Oncogene or CCND1) targeted therapeutics under development by companies and universities/research institutes based on information derived from company and industry-specific sources. (globalmarketsdirect.com)
- The report reviews key players involved in G1/S Specific Cyclin D1 (B Cell Lymphoma 1 Protein or BCL 1 Oncogene or PRAD1 Oncogene or CCND1) targeted therapeutics and enlists all their major and minor projects. (globalmarketsdirect.com)
- The report assesses G1/S Specific Cyclin D1 (B Cell Lymphoma 1 Protein or BCL 1 Oncogene or PRAD1 Oncogene or CCND1) targeted therapeutics based on Mechanism of Action (MoA), Route of Administration (RoA) and Molecule Type. (globalmarketsdirect.com)
- The report reviews latest news and deals related to G1/S Specific Cyclin D1 (B Cell Lymphoma 1 Protein or BCL 1 Oncogene or PRAD1 Oncogene or CCND1) targeted therapeutics. (globalmarketsdirect.com)
- Identify and understand the targeted therapy areas and indications for G1/S Specific Cyclin D1 (B Cell Lymphoma 1 Protein or BCL 1 Oncogene or PRAD1 Oncogene or CCND1). (globalmarketsdirect.com)
- Proto-Oncogene Proteins c-bcl-2" is a descriptor in the National Library of Medicine's controlled vocabulary thesaurus, MeSH (Medical Subject Headings) . (rush.edu)
- This graph shows the total number of publications written about "Proto-Oncogene Proteins c-bcl-2" by people in this website by year, and whether "Proto-Oncogene Proteins c-bcl-2" was a major or minor topic of these publications. (rush.edu)
- Below are the most recent publications written about "Proto-Oncogene Proteins c-bcl-2" by people in Profiles. (rush.edu)
- This review is limited in scope to the intrinsic pathway and its regulation by BCL-2 family of proteins. (aacrjournals.org)
- In the other, Roy have presented a comprehensive review of compounds that target the BCL-2 family-driven pathway . (immune-source.com)
- The ER responds to disturbances in its homeostasis by launching an adaptive signal transduction pathway, known as the unfolded protein response (UPR). (physiology.org)
- A major finding of our article is that the p53/p21 complex is a functional unit that can act on multiple cellular components and that prosurvival Bcl-2 proteins are targets of the p53/p21 complex. (aacrjournals.org)
- More than 15 cellular Bcl-2-related proteins have been identified in a wide range of species. (asm.org)
- The E6 oncoprotein forms a complex with the cellular tumor suppressor protein p53, leading to degradation of p53 via ubiquitin-dependent proteolysis. (aacrjournals.org)
- Thus, we provide the first definitive in vivo evidence that prosurvival proteins maintain cellular viability by interacting with and inhibiting Bak. (rcsb.org)
- We further show that mebendazole-resistant melanocytes can be sensitized through reduction of Bcl-2 protein levels, showing the essential role of Bcl-2 in the cellular response to mebendazole-mediated tubulin disruption. (aacrjournals.org)
- To prevent the cellular milieu from clogging up, damaged or "out-ofwork" organelles and misfolded proteins are sequestered in doublemembrane vesicles called autophagosomes and delivered to cytosolic lysosomes for degradation of intracellular contents [ 1 ]. (omicsonline.org)
- Bcl-2 antiapoptotic proteins inhibit Beclin 1-dependent autophagy. (nih.gov)
- Furthermore, Beclin 1 mutants that cannot bind to Bcl-2 induce more autophagy than wild-type Beclin 1 and, unlike wild-type Beclin 1, promote cell death. (nih.gov)
- This cell death was inhibited by knockdown of the autophagy protein ATG5 by RNAi. (sciencemag.org)
- Among the proteins involved in this response are nutrient-deprivation autophagy factor-1 (NAF-1)- and Bcl-2. (sigmaaldrich.com)
- NAF-1 is an important partner for Bcl-2 at the endoplasmic reticulum to functionally antagonize Beclin 1-dependent autophagy [Chang NC, Nguyen M, Germain M, Shore GC (2010) EMBO J 29(3):606-618]. (sigmaaldrich.com)
- In addition, ER stress is also known to induce autophagy to counteract XBP-1-mediated ER expansion and assist in the degradation of unfolded proteins. (physiology.org)
- Autophagy related proteins are Beclin-1, a human tumour suppressor, Bcl-2 and p 62 have been characterised in most cancers. (omicsonline.org)
- The p53 protein is a transcription factor that, when activated as part of the cell's response to stress, regulates many downstream target genes, including BAX. (wikipedia.org)
- Abnormalities to the regulation of this cell death process, including mutations to genes for BCL‐2 family members, can lead to a disease, such as cancer. (els.net)
- Rapid acclimation of juvenile corals to CO2-mediated acidification by upregulation of heat shock protein and Bcl-2 genes. (coralcoe.org.au)
- The t(14;18) translocation results in a hybrid bcl-2/immunoglobulin heavy chain transcript consisting of the 5' half of the bcl-2 mRNA fused to a truncated immunoglobulin heavy chain mRNA. (thefreedictionary.com)
- 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. (uchicago.edu)
- Although all have a BH3 motif (green), antiapoptotic BCL‐2 family members and the proapoptotic proteins BAX , BAK and Bok , all bear a BH1 (yellow), a BH2 (blue), a BH3 (green) and a BH4 (red) motif. (els.net)
- Boxed sequences indicate the 26-mer peptides used to measure the affinities of the mutant BH3 peptides for mouse Bcl-x L , Mcl-1, and Bax. (rupress.org)
- 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)
- Bcl-2 family members are essential for maintenance of major organ systems, and mutations affecting them are implicated in cancer. (sciencemag.org)
- Understanding the roles of BCL‐2 family members, their structures and how they interact, has allowed the development of novel agents for the treatment of cancer that are now in clinical trials. (els.net)
- All BCL‐2 family members bear a number of BCL‐2 homology (BH) motifs. (els.net)
- Most BCL‐2 family members also have a hydrophobic region at the carboxy‐terminus (grey) that can act as a transmembrane domain. (els.net)
- When antiapoptotic BCL‐2 family members and the proapoptotic multiple BH motif containing proteins fold, the BH3 , BH1 and BH2 motifs form a hydrophobic pocket (depicted as indentations in the diagrams on the right) that is capable of binding to the BH3 α helices (depicted as fingers) of other BCL‐2 family members. (els.net)
- Note that Bcl‐x, like all multidomain BCL‐2 family members, is almost entirely composed of α helices. (els.net)
- We provide the first structural explanation for the conformational flexibility of the BCL-W groove region in comparison to other BCL-2 family members. (rcsb.org)
- At least 20 different Bcl-2 family members have been reported, acting as death antagonist or agonist proteins. (scielo.br)
- Antibody products for detection of many of the above listed bcl-2 family members are available at OriGene Technologies. (acris-antibodies.com)
- The Bcl-2 protein and other family members target intracellular organelles such as the endoplasmic reticulum and the outer mitochondrial and nuclear membranes, where they modulate responses to diverse death stimuli. (bmj.com)
- Complex of Bcl‐x (blue) with the BH3 helix peptide from BAK (red). (els.net)
- There was no consideration of how the p53/p21/Bcl-w complex might relate to p53/MDM2 or p21/cyclin/CDK/PCNA complexes. (aacrjournals.org)
- 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)
- We now determined two high-resolution crystal structures of human BCL-W in complex with different DARPins at resolutions 1.5 and 1.85Å, in which the structure of BCL-W is virtually identical, and BCL-W adopts a conformation extremely similar to the ligand-free conformation of its closest relative BCL-XL in both structures. (rcsb.org)
- After the primary antibody is bound to the target protein, a complex with HRP-linked secondary antibody is formed. (cellsignal.com)
- Recent studies suggest that it can mediate the death function of tumor suppressor p53 and is activated by a multimeric protein complex, PIDDosome. (elsevier.com)
- Our lab studies various aspects of this complex and unique biology, including the modulation of Bcl-2 family activity for potential therapeutic benefit in cancer. (mcgill.ca)
- Integrated strategy reveals the protein interface between cancer targets Bcl-2 and NAF-1. (sigmaaldrich.com)
- I will provide an overview of the functions of this family of proteins and their targets, and will discuss a possible molecular approach for the prevention of neurodegenerative diseases. (springer.com)
- In particular, recent advances in understanding the interplay between distinct members of the BCL-2 family and the molecular mechanisms underlying their regulation of MOMP are described. (aacrjournals.org)
- 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)
- However, recent work has revealed that certain members of the Bcl-2 family are present on the ER where they seem to have a much broader and more comprehensive function. (physiology.org)
- Here, we review the involvement of proteins from each of the three Bcl-2 family subgroups in the maintenance of ER homeostasis and their participation in ER stress signal transduction pathways. (physiology.org)
- Artificial BCL‐2 antagonists, such as ABT‐263 (light blue) can act like BH3‐only proteins by binding to antiapoptotic BCL‐2 family proteins. (els.net)
- 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)
- Bcl-2 was first described in follicular lymphomas with t(14;18) translocation (4). (scielo.br)
- Bcl-2 is over expressed in follicular lymphomas with the translocation t(14;18)(q32;q21), detected in 70 to 95% of follicular lymphomas and 20% of diffuse large B cell lymphomas. (thefreedictionary.com)
- All tested herpesvirus Bcl-2 homologs possess antiapoptotic activity, including the more distantly related homologs encoded by murine gammaherpesvirus 68 (γHV68) and bovine herpesvirus 4 (BHV4), as described here. (asm.org)
- The molecular pathogenesis of HPV was analyzed by correlating the data with the expressions of different cell cycle associated molecules such as p53, bcl-2 and PCNA in the biopsy. (abebooks.com)
- ii)HPV infection establishes its carcinogenicity through altered cell cycle control molecules such as p53, bcl-2 and PCNA iii)Retinoid ATRA level has a major role during carcinogenesis and it was found to be associated with the oncopotency of HPV types. (abebooks.com)
- Both molecules are authentic BH3 mimetics targeting BCL-2, BCL-XL and BCL-W but not MCL-1 or A1 (as the BH3-only protein BAD, so they are referred to as BAD-like BH3 mimetics). (immune-source.com)
- The endoplasmic reticulum (ER) is the main site for protein folding, lipid biosynthesis, and calcium storage in the cell. (physiology.org)
- To capture its ligand binding-competent conformation by counteracting the conformational flexibility of the BCL-W groove, we had selected high-affinity groove-binding designed ankyrin repeat proteins (DARPins) using ribosome display. (rcsb.org)
- Furthermore, the chemical shift perturbations on Bcl-w, Mcl-1, and Bcl-2 induced by p53DBD binding occurred not only at the p53DBD-binding acidic region but also at the BH3 peptide-binding pocket, which suggests an allosteric conformational change similar to that observed in Bcl-XL. (ntu.edu.sg)
- Herein, we identified the polypyrimidine tract binding protein (PTBP1) as a direct regulator of BCL-X AS. (unboundmedicine.com)
Release of apoptogenic proteins1
- 19 The opening of this pore, known as mitochondrial permeability transition, is associated with the release of apoptogenic proteins. (bmj.com)
- p53 is believed to be the most important tumor suppressor protein and abnormality of p53 causes cancers and many other diseases. (ntu.edu.sg)
- The bar plot below shows the proportion of tumor samples that have any kind of altering mutation(s) in the given protein. (phosphosite.org)
- Tumor suppressor protein p53. (scielo.br)
- Here, we found a marked increase in mitochondrial B-cell lymphoma-2 (Bcl-2) in lung macrophages from subjects with idiopathic pulmonary fibrosis (IPF). (nature.com)
- Additional investigation of the molecular mechanisms of synergy revealed an association with the down-regulation of Bcl-2 in AIDS-related lymphoma (ARL) ( 7 , 8 ) or of Bcl-x L in non-ARL cell lines ( 9 , 10 ). (jimmunol.org)
- The founding member of the Bcl-2 protein family, Bcl-2 itself, was discovered during molecular analysis of the t14-18 chromosomal translocation in B cell lymphoma ( 133 ). (physiology.org)