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CIAP1 and the serine protease HTRA2 are involved in a novel p53-dependent apoptosis pathway in mammals.

ABSTRACT: 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.

SUBMITTER: Jin S

PROVIDER: S-EPMC195984 | biostudies-literature | 2003 Feb

REPOSITORIES: biostudies-literature

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CIAP1 and the serine protease HTRA2 are involved in a novel p53-dependent apoptosis pathway in mammals.

Jin Shengkan S Kalkum Markus M Overholtzer Michael M Stoffel Archontoula A Chait Brian T BT Levine Arnold J AJ

Genes & development 20030201 3

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. Furthe ...[more]

PMID: 12569127

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