| Autor: |
Grandgirard, Denis, Studer, Erwin, Monney, Laurent, Belser, Tanja, Fellay, Isabelle, Borner, Christoph, Michel, Marcel R. |
| Předmět: |
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| Zdroj: |
EMBO Journal; 3/1/98, Vol. 17 Issue 5, p1268-1278, 11p |
| Abstrakt: |
Bcl-2 oncogene expression plays a role in the establishment of persistent viral infection by blocking virus-induced apoptosis. This might be achieved by preventing virus-induced activation of caspase-3, an IL-1β-converting enzyme (ICE)-like cysteine protease that has been implicated in the death effector phase of apoptosis. Contrary to this model, we show that three cell types highly overexpressing functional Bcl-2 displayed caspase-3 activation and underwent apoptosis in response to infection with alphaviruses Semliki Forest and Sindbis as efficiently as vector control counterparts. In all three cell types, overexpressed 26 kDa Bcl-2 was cleaved into a 23 kDa protein. Antibody epitope mapping revealed that cleavage occurred at one or two target sites for caspases within the amino acid region YEWD31· AGD34· A, removing the N-terminal BH4 region known to be essential for the death-protective activity of Bcl-2. Preincubation of cells with the caspase inhibitor Z-VAD prevented Bcl-2 cleavage and partially restored the protective activity of Bcl-2 against virus-induced apoptosis. Moreover, a murine Bcl-2 mutant having Asp31, Asp34 and Asp36 substituted by Glu was resistant to proteolytic cleavage and abrogated apoptosis following virus infection. These findings indicate that alphaviruses can trigger a caspasemediated inactivation of Bcl-2 in order to evade the death protection imposed by this survival factor. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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