XIAP regulates DNA damage-induced apoptosis downstream of caspase-9 cleavage

R. Datta, E. Oki, K. Endo, V. Biedermann, J. Ren, D. Kufe

Research output: Contribution to journalArticle

87 Citations (Scopus)

Abstract

The IAP (inhibitor of apoptosis) family of anti-apoptotic proteins regulates programmed cell death. Of the six known human LAP-related proteins, XIAP is the most potent inhibitor. To study the mechanistic effects of XIAP on DNA damage-induced apoptosis, we prepared U-937 cells that stably overexpress XIAP. The results demonstrate that XIAP inhibits apoptosis induced by 1-[β-D-arabinofuranosyl]cytosine (ara-C) and other genotoxic agents. XIAP had no detectable effect on ara-C-induced release of mitochondrial cytochrome c and attenuated cleavage of precaspase-9. In addition, we show that ara-C induces the association of XIAP with the cleaved fragments of caspase-9 and thereby inhibition of caspase-9 activity. The results also demonstrate that ara-C induces cleavage of procaspase-3 by a caspase-8-dependent mechanism and that XIAP inhibits caspase-3 activity. These results demonstrate that functions downstream of procaspase-9 cleavage as an inhibitor of both proteolytically processed caspase-9 and -3 in the cellular response to genotoxic stress.

Original languageEnglish
Pages (from-to)31733-31738
Number of pages6
JournalJournal of Biological Chemistry
Volume275
Issue number41
DOIs
Publication statusPublished - Oct 13 2000
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'XIAP regulates DNA damage-induced apoptosis downstream of caspase-9 cleavage'. Together they form a unique fingerprint.

  • Cite this