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| FAS-INDUCED AND TUMOR NECROSIS FACTOR-INDUCED APOPTOSIS IS INHIBITED BY THE POXVIRUS CRMA GENE-PRODUCT |
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| Author(s): TEWARI M, DIXIT VM |
| Source: JOURNAL OF BIOLOGICAL CHEMISTRY Volume: 270 Issue: 7 Pages: 3255-3260 Published: FEB 17 1995 |
| Times Cited: 562 References: 34 |
| Abstract: crmA is a cowpox virus gene that encodes a protease inhibitor of the serpin family, The only reported target for the CrmA protein is the cysteine protease interleukin-1 beta converting enzyme (ICE). ICE, by virtue of its homology to the Caenorhabditis elegans cell death protein Ced-3, has been suggested to play a fundamentally important role in mammalian apoptosis. We hypothe sized that a function of crmA may be to inhibit cell death, since a major mechanism of viral clearance is the immune system-mediated induction of apoptosis of infected cells. The tumor necrosis factor receptor and the Fas antigen are two cytokine receptors which, by engaging and activating the death pathway, can eliminate virus-infected cells. Remarkably, crmA was found to be an exceptionally potent inhibitor of apoptosis induced by both these receptors, capable of blocking the cell death program even at pharmacological doses of the death stimulus. Therefore, an important new function for crmA is the inhibition of cytokine-induced apoptosis. Further, the data suggest that a protease, either ICE or a related crmA-inhibitable protein, is a component of the Fas- and tumor necrosis factor-induced cell death pathways. |
| Document Type: Article |
| Language: English |
Addresses:
1. UNIV MICHIGAN, SCH MED, DEPT PATHOL, ANN ARBOR, MI 48109 USA
2. UNIV MICHIGAN, SCH MED, GRAD PROGRAM CELLULAR & MOLEC BIOL, ANN ARBOR, MI 48109 USA |
| Publisher: AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA |
| Subject Category: Biochemistry & Molecular Biology |
| IDS Number: QG471 |
| ISSN: 0021-9258 |
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