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Science. 2000 May 5;288(5467):874-7.

Ubiquitin protein ligase activity of IAPs and their degradation in proteasomes in response to apoptotic stimuli.

Author information

1
Laboratory of Immune Cell Biology, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.

Abstract

To determine why proteasome inhibitors prevent thymocyte death, we examined whether proteasomes degrade anti-apoptotic molecules in cells induced to undergo apoptosis. The c-IAP1 and XIAP inhibitors of apoptosis were selectively lost in glucocorticoid- or etoposide-treated thymocytes in a proteasome-dependent manner before death. IAPs catalyzed their own ubiquitination in vitro, an activity requiring the RING domain. Overexpressed wild-type c-IAP1, but not a RING domain mutant, was spontaneously ubiquitinated and degraded, and stably expressed XIAP lacking the RING domain was relatively resistant to apoptosis-induced degradation and, correspondingly, more effective at preventing apoptosis than wild-type XIAP. Autoubiquitination and degradation of IAPs may be a key event in the apoptotic program.

PMID:
10797013
[Indexed for MEDLINE]
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