Bcl-2 and Fas/APO-1 regulate distinct pathways to lymphocyte apoptosis
- Author(s)
- Strasser, A; Harris, AW; Huang, DCS; Krammer, PH; Cory, S;
- Details
- Publication Year 1995-12-15,Volume 14,Issue #24,Page 6136-6147
- Journal Title
- EMBO JOURNAL
- Publication Type
- Journal Article
- Abstract
- Activation of the cell surface receptor Fas/APO-1 (CD95) induces apoptosis in lymphocytes and regulates immune responses. The cytoplasmic membrane protein Bcl-2 inhibits lymphocyte killing by diverse cytotoxic agents, but we found it provided little protection against Fas/APO-1-transduced apoptosis in B lymphoid cell lines, thymocytes and activated T cells. In contrast, the cowpox virus protease inhibitor CrmA blocked Fas/APO-1-transduced apoptosis, but did not affect cell death induced by gamma-radiation or serum deprivation. Signalling through Fas/APO-1 did not down-regulate Bcl-2 or induce its antagonists Bar and Bcl-x(S). In Fas/APO-1-deficient lpr mice, Bcl-2 transgenes markedly augmented the survival of antigen-activated T cells and the abnormal accumulation of lymphocytes (although they did not interfere with deletion of autoreactive cells in the thymus). These data raise the possibility that Bcl-2 and Fas/APO-1 regulate distinct pathways to lymphocyte apoptosis.
- Publisher
- OXFORD UNIV PRESS UNITED KINGDOM
- Keywords
- TUMOR-NECROSIS-FACTOR; PROGRAMMED CELL-DEATH; MATURE T-CELLS; FAS ANTIGEN; MONOCLONAL-ANTIBODY; SURFACE ANTIGEN; FACTOR RECEPTOR; GENE CED-3; MICE; PROTEIN
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- Refer to copyright notice on published article.
Creation Date: 1995-12-15 12:00:00