Journal
GENES & DEVELOPMENT
Volume 17, Issue 3, Pages 359-367Publisher
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1101/gad.1047003
Keywords
inhibitor of apoptosis (IAP); CIAP1; serine protease HTRA2; p53-dependent apoptosis; AEBSF; z-VAD
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Funding
- NCI NIH HHS [P01 CA087497, 1R33CA89810-01, R33 CA089810, P01CA87497] Funding Source: Medline
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Recently a Drosophila p53 protein has been identified that mediates apoptosis via a novel pathway involving the activation of the Reaper gene and subsequent inhibition of the inhibitors of apoptosis (IAPs). The present study found that CIAP1, a major mammalian homolog of Drosophila IAPs, is irreversibly inhibited (cleaved) during p53-dependent apoptosis and this cleavage is mediated by a serine protease. Serine protease inhibitors that block CIAP1 cleavage inhibit p53-dependent apoptosis. Furthermore, activation of the p53 protein increases the transcription of the HTRA2 gene, which encodes a serine protease that interacts with CIAP1 and potentiates apoptosis. These results demonstrate that the mammalian p53 protein may activate apoptosis through a novel pathway functionally similar to that in Drosophila, which involves HTRA2 and subsequent inhibition of CIAP1 by cleavage.
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