Ubiquitin protein ligase activity of IAPs and their degradation in proteasomes in response to apoptotic stimuli.
Science
; 288(5467): 874-7, 2000 May 05.
Article
en En
| MEDLINE
| ID: mdl-10797013
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.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Cisteína Endopeptidasas
/
Linfocitos T
/
Proteínas
/
Apoptosis
/
Ligasas
/
Complejos Multienzimáticos
Límite:
Animals
Idioma:
En
Revista:
Science
Año:
2000
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Estados Unidos