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- Title
Ubiquitin protein ligase activity of IAPs and their degradation in proteasomes in response to apoptotic stimuli.
- Authors
Yang, Y; Fang, S; Jensen, J P; Weissman, A M; Ashwell, J D
- 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.
- Publication
Science (New York, N.Y.), 2000, Vol 288, Issue 5467, p874
- ISSN
0036-8075
- Publication type
Journal Article
- DOI
10.1126/science.288.5467.874