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

Shengkan Jin, Markus Kalkum, Michael Overholtzer, Archontoula Stoffel, Brian T. Chait, Arnold J. Levine

Research output: Contribution to journalArticlepeer-review

76 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)359-367
Number of pages9
JournalGenes and Development
Volume17
Issue number3
DOIs
StatePublished - Feb 1 2003
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Genetics
  • Developmental Biology

Keywords

  • AEBSF
  • CIAP1
  • Inhibitor of apoptosis (IAP)
  • P53-dependent apoptosis
  • Serine protease HTRA2
  • Z-VAD

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