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Query: UNIPROT:P10415 (Bcl-2)
 33,771 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The expression and functions of Fas antigen, a major regulator of apoptosis, in T-cell selection have been intensively investigated, but little is known about its expression i immature B cells which are also selected in the bone marrow, and plasma cells which are at the terminal stage of B-cell differentiation and are designed to die. We examined bone marrow cells and found Fas antigen on these cells at low levels. Next we analysed Fas expression and susceptibility to anti-Fas antibody-mediated apoptosis on B-cell lines representing various stages of differentiation. We also examined the expression of Bcl-2 and Bax on these lines, which were intimately related to apoptosis. Fas antigen was almost negative on pre-pre-B cell lines and was detected on pre-B-cell lines at low levels. All plasma cell lines expressed Fas at a low to moderate level. Some cell lines with peripheral B-cell phenotype expressed Fas antigen. Except for the Burkitt cell lines and one plasma cell line, susceptibility to Fas-mediated apoptosis depended on Fas expression. Bcl-protein was detected on all but one cell line and Bax was detected on 15/23 lines, but neither were related to cellular differentiation or Fas expression.
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PMID:The Fas antigen is detected on immature B cells and the representative cell lines show Fas-mediated apoptosis. 860 89

Mice defective in Fas (CD95 or APO-1) or its ligand (lpr or gld mice) develop age-dependent lymphadenopathy and systemic autoimmune disease. T cells accumulating in the lymph nodes of these mice express reduced levels of Bcl-2 protein and are susceptible to spontaneous and glucocorticoid-induced apoptosis. We backcrossed bcl-2 transgenic mice to lpr and gld mice to homozygosity to determine the effects of Bcl-2 overexpression. T cells in these mice were resistant to spontaneous and glucocorticoid-induced apoptosis in vitro. Moreover, the accumulation of CD4(-)CD8(-) T cells in the lymph nodes and the spleens was augmented, suggesting that a Bcl-2-dependent mechanism regulating the number of T cells residing in the peripheral lymphoid organs in addition to the Fas-mediated pathway exists.
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PMID:Inhibition of apoptosis and augmentation of lymphoproliferation in bcl-2 transgenic Fas/Fas ligand-defective mice. 864 Aug 68

Stimulation of the Fas (APO-1, CD95) receptor, which is present on a variety of cells, usually triggers a process of programmed cell death. Systemic injection of anti-Fas antibody into mice leads to fulminant liver destruction resulting from massive hepatocyte apoptosis, and to rapid death. Hepatocytes bear Fas but do not express Bcl-2, a protein that plays, in a number of conditions, a protective role against apoptosis. We have generated mice whose liver expresses Bcl-2 as the result of bcl-2 transgene placed under the control of the hepatocyte-specific alpha1-anti-trypsin gene promoter, but is otherwise not distinguishable from that of normal mice. These mice display a marked to almost total resistance to liver damage induced by anti-Fas antibody injection. This protective effect of Bcl-2 occurs in the absence of significant variations, in the stimulated livers, in the level of expression of other proteins also involved in resistance or sensitivity to apoptosis, namely Bcl-x, Bax, Bad, Bak, and p53. Mice with protected livers, however, die almost as rapidly as normal mice, which indicates that acute lethality results from stimulation of Fas receptors present on other target organs or cells.
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PMID:A bcl-2 transgene expressed in hepatocytes protects mice from fulminant liver destruction but not from rapid death induced by anti-Fas antibody injection. 864 44

The human proto-oncogene bcl-2 and its Caenorhabditis elegans homologue ced-9 inhibit programmed cell death. In contrast, members of the human interleukin-1beta converting enzyme (ICE) family of cysteine proteases and their C. elegans homologue CED-3 promote the death program. Genetic experiments in C. elegans have shown that ced-9 is formally a negative regulator of ced-3 function, but neither those studies nor others have determined whether CED-9 or Bcl-2 proteins act biochemically upstream or downstream of CED-3/ICE proteases. CPP32, like all known members of the CED-3/ICE family, is synthesized as a proenzyme that is subsequently processed into an active protease with specificity for cleavage at Asp-X peptide bonds. In this report, we demonstrate that the CPP32 proenzyme is proteolytically processed and activated in Jurkat cells induced to die by Fas ligation. CPP32 activation is blocked by cell-permeable inhibitors of aspartate-directed, cysteine proteases, suggesting that pro-CPP32 is cleaved by active CPP32 or by other ICE family members. Heterologous expression of Bcl-2 in Jurkat cells prevents Fas-induced cell death as well as proteolytic processing and activation of CPP32. Thus, Bcl-2 acts at or upstream of the CPP32 activation step to inhibit apoptosis induced by Fas stimulation.
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PMID:Fas-induced activation of the cell death-related protease CPP32 Is inhibited by Bcl-2 and by ICE family protease inhibitors. 866 39

Antigen-activated T cells of the CD4(+)CD8(-) phenotype are susceptible to antigen receptor-stimulated cell death. This form of apoptotic cell death has been shown to be dependent on the expression of the Fas (CD95) antigen and can occur via an autocrine mechanism involving the concomitant up-regulation of Fas and its ligand on activated T cells. Mutation in genes encoding Fas (Ipr) and the Fas ligand (gld) contribute to the development of an autoimmune syndrome similar to systemic lupus erythematosus in mice. These observations led to the suggestion that the Fas signaling pathway is an important regulator of immune responses in vivo. Here we evaluated the importance of the Fas pathway in regulating immune responses by male antigen-specific CD4(-)CD8(+) T cells. We found that the in vivo elimination of these activated cells was independent of Fas expression by these cells. However, the elimination of these activated cells was inhibited by the transgenic expression of Bcl-2, a protein that inhibits multiple forms of apoptotic cell death. The transgenic Bcl-2 protein also inhibited the death of male antigen-activated cells following IL-2 deprivation. Cell death resulting from IL-2 deprivation occurred efficiently in male antigen-activated Fas- cells. We propose that the rapid deletion of male antigen-activated Fas- cells in vivo is due to limiting amounts of IL-2 that are available in the microenvironment of the activated cells at the peak of the response.
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PMID:Fas (CD95)-independent regulation of immune responses by antigen-specific CD4-CD8+ T cells. 867 54

In this study, we have investigated whether the enhanced apoptosis of CD4+ and CD8+ T lymphocytes throughout HIV infection was controlled by the bcl-2 proto-oncogene, an inhibitor of programmed cell death (PCD) in mammals. We have analyzed the intracellular expression of the Bcl-2 protein by flow cytometry in freshly isolated peripheral T cells from HIV-infected and noninfected individuals. While no decrease in Bcl-2 expression was detected in the CD4+ T cell subset from the seropositive donors, a reduced level of Bcl-2 was found in a fraction of CD8+ T lymphocytes, with the proportion of these cells increasing as HIV infection progressed. We show that the low Bcl-2-expressing CD8+ T cells were highly susceptible to spontaneous apoptosis upon short term culture. Interestingly, PCD significantly increased when these lymphocytes were cultured in the presence of a Fas-specific mAb, which was related to the high expression of the Fas Ag on their surface. The low Bcl-2 CD8+ subpopulation displayed activation markers CD45RO, HLA-DR, and CD38 and expressed TIA-1-positive, but perforin-negative, granules, while lacking the CD28 Ag. These observations suggest that such low Bcl-2 CD8+ T cells correspond to either immature or end-staged anergic CTLs. Moreover, they indicate that down-regulation of Bcl-2 and up-regulation of Bcl-2 and up-regulation of Fas in CD8+ T lymphocytes, associated with the chronic stimulation of these cells during HIV infection, might render them sensitive to Fas-mediated PCD. Such a Bcl-2/Fas-regulated apoptosis could be responsible for the disappearance of both memory CD45RO+ T cell response and HIV-specific cytotoxic activity occurring in the course of HIV infection and could contribute to AIDS pathogenesis.
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PMID:Apoptosis associated with ex vivo down-regulation of Bcl-2 and up-regulation of Fas in potential cytotoxic CD8+ T lymphocytes during HIV infection. 869 Sep 19

Galectin-3 is a member (if a large family of beta-galactoside-binding animal lectins. It has been shown that the expression of galectin-3 is upregulated in proliferating cells, suggesting a possible role for this lectin in regulation of cell growth. Previously, we have shown that T cells infected with human T-cell leukemia virus type I express high levels of galectin-3, in contrast to uninfected cells, which do not express detectable amounts of this protein. In this study, we examined growth properties of human leukemia T cells transfected with galectin-3 cDNA, and thus constitutively overexpressing this lectin. Transfectants expressing galectin-3 displayed higher growth rates than control transfectants, which do not express this lectin. Furthermore, galectin-3 expression in these cells confers resistance to apoptosis induced by anti-Fas antibody and staurosporine. Galectin-3 was found to have significant sequence similarity with Bcl-2, a well-characterized suppressor of apoptosis. In particular, the lectin contains the NWGR motif that is highly conserved among members of the Bcl-2 family and shown to be critical for the apoptosis-suppressing activity. We further demonstrated that galectin-3 interacts with Bc1-2 in a lactose-inhibitable manner. We conclude that galectin-3 is a regulator of cell growth and apoptosis and it may function through a cell death inhibition pathway that involves Bcl-2.
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PMID:Expression of galectin-3 modulates T-cell growth and apoptosis. 869 88

Suppression of apoptosis by Bcl-2, an oncogene product, has been previously reported. Although the down regulation of Bcl-2 has been encountered in various types of apoptosis, the time course of changes in the expression of Bcl-2 has yet to be determined. In the present study, we established and analysed an in vivo model of apoptosis. The mouse male reproductive tract, specifically the prostate and epididymis, which is regulated by sex steroid hormones, especially testosterone, showed regression induced by chromosomal DNA fragmentation, apoptotic cell death, after gonadectomy. Following this apoptosis, down regulation of Bcl-2 and the new expression of Fas were seen. Using functional Fas-lacking mice, we demonstrated that this regression of the male reproductive tract is triggered by Fas-mediated apoptosis. In addition, time course experiments revealed that down regulation of Bcl-2 when apoptosis occurs heralds Fas expression. We propose here that apoptotic death signal transduction in total involve, a number of steps, the first and most important of which is down regulation of Bcl-2.
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PMID:Down regulation of Bcl-2 is the first step on Fas-mediated apoptosis of male reproductive tract. 870 May 51

Mutation, deactivation and disregulated expression of oncogenes and tumour-suppressor genes may be involved in the pathogenesis of oral squamous cell carcinoma (SCC). Deactivation of the p53 tumour-suppressor gene allows cell proliferation and blocks apoptosis of malignant oral keratinocytes. Mutation in the ras oncogene results in persistent mitogenic signalling. Upregulatioed c-Myc expression, in the presence of growth factors, provides an additional proliferative signal. Loss of retinoblastoma tumour-suppressor gene (Rb) function may contribute to oral keratinocyte hyperproliferation and recent evidence suggests that simultaneous deactivation of both p53 and Rb is required for tumourigenesis. Enhanced Bcl-2 and reduced Fas expression inhibit tumour cell apoptosis and may convey resistance to cytotoxic drugs and T cell-mediated cytotoxicity, respectively. Exogenous mutagens such as tobacco, alcohol and viral oncogenes may cause altered expression of oncogenes and tumour-suppressor genes in some cases of oral SCC. The impact of these mechanisms on future therapies for oral SCC is highlighted.
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PMID:Review article: The role of oncogenes, tumour suppressor genes and growth factors in oral squamous cell carcinoma: a case of apoptosis versus proliferation. 870 24

We investigated the expression of Fas(CD95) on hematopoietic progenitor cells. CD34+ cells freshly isolated from bone marrow did not express Fas. However, interferon-gamma(IFN-gamma) and/or tumor necrosis factor-alpha (TNF-alpha) induced the expression of Fas after 48 hours of serum-free culture. The TNF-alpha-induced Fas expression is mediated by p55-TNF-alpha receptor. Human CD34+ cells expressed Fas following low dose ionizing radiation in a dose-dependent fashion. CD34+ cells isolated from bone marrow were cultured with hematopoietic growth factors for 7 days. CD34+ cells cultured with hematopoietic growth factors gradually became positive for Fas and rapidly lost Bcl-2 expression. Fas system is considered to play important roles at the level of hematopoietic progenitor cells in both physiologic and pathologic conditions.
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PMID:[Fas antigen expression on human hematopoietic progenitor cells]. 874 68


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