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Published on: June 25, 2015
The baculovirus p35 protein inhibits Fas- and tumor necrosis factor-induced apoptosis
D R Beidler1, M Tewari, P D Friesen
1Department of Pathology, University of Michigan Medical School, Ann Arbor 48109, USA.
Abstract:
The baculovirus p35 gene product inhibits virally induced apoptosis, developmental cell death in Caenorhabditis elegans and Drosophila, and neuronal cell death in mammalian systems. Therefore, p35 likely inhibits a component of the death machinery that is both ubiquitous and highly conserved in evolution. We now show for the first time that p35 also inhibits Fas- and tumor necrosis factor (TNF)-induced apoptosis. Additionally, p35 blocks TNF- and Fas-induced proteolytic cleavage of the death substrate poly(ADP-ribose) polymerase from its native 116-kDa form to the characteristic 85-kDa form. This cleavage is thought to be catalyzed by an aspartate-specific protease of the interleukin 1 beta-converting enzyme family designated prICE (Lazebnik, Y. A., Kaufmann, S. H., Desnoyers, S., Poirier, G. G., and Earnshaw, W. C. (1994) Nature 371, 346-347). Our data suggest that p35 must directly or indirectly inhibit prICE. Given that p35 inhibits both TNF and Fas killing, along with previous reports of its ability to block developmental, viral, and x-irradiation-induced cell death, the present results indicate that TNF- and Fas-mediated apoptotic pathways must have components in common with these highly conserved death programs.
Insights
The baculovirus p35 protein inhibits apoptosis across diverse systems, including viral, developmental, and neuronal cell death. This study demonstrates p35 also blocks Fas and tumor necrosis factor (TNF)-induced apoptosis by inhibiting prICE, a key protease.
Area of Science:
- Cell Biology
- Molecular Biology
- Virology
Background:
- The baculovirus p35 gene product is known to inhibit apoptosis induced by viruses, developmental processes, and in mammalian neuronal cells.
- This suggests p35 targets a conserved component of the cell death machinery.
Purpose of the Study:
- To investigate the role of p35 in Fas- and tumor necrosis factor (TNF)-induced apoptosis.
- To determine if p35 affects the proteolytic cleavage of poly(ADP-ribose) polymerase (PARP).
Main Methods:
- Experiments were conducted to assess the inhibitory effects of p35 on Fas- and TNF-induced apoptosis.
- Proteolytic cleavage of PARP was analyzed in the presence and absence of p35.
Main Results:
- p35 was shown to inhibit both Fas- and TNF-induced apoptosis.
- p35 blocked the cleavage of PARP from its 116-kDa to 85-kDa form, a process mediated by prICE.
- These findings suggest p35 directly or indirectly inhibits prICE.
Conclusions:
- The results indicate that TNF- and Fas-mediated apoptotic pathways share common components with other conserved death programs.
- p35's inhibition of prICE highlights its crucial role in regulating apoptosis across various pathways.
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