Molecular determinants of the caspase-promoting activity of Smac/DIABLO and its role in the death receptor pathway.
J Biol Chem
; 275(46): 36152-7, 2000 Nov 17.
Article
en En
| MEDLINE
| ID: mdl-10950947
ABSTRACT
Smac/DIABLO is a mitochondrial protein that is released along with cytochrome c during apoptosis and promotes cytochrome c-dependent caspase activation by neutralizing inhibitor of apoptosis proteins (IAPs). We provide evidence that Smac/DIABLO functions at the levels of both the Apaf-1-caspase-9 apoptosome and effector caspases. The N terminus of Smac/DIABLO is absolutely required for its ability to interact with the baculovirus IAP repeat (BIR3) of XIAP and to promote cytochrome c-dependent caspase activation. However, it is less critical for its ability to interact with BIR1/BIR2 of XIAP and to promote the activity of the effector caspases. Consistent with the ability of Smac/DIABLO to function at the level of the effector caspases, expression of a cytosolic Smac/DIABLO in Type II cells allowed TRAIL to bypass Bcl-xL inhibition of death receptor-induced apoptosis. Combined, these data suggest that Smac/DIABLO plays a critical role in neutralizing IAP inhibition of the effector caspases in the death receptor pathway of Type II cells.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Transducción de Señal
/
Proteínas Portadoras
/
Apoptosis
/
Receptores del Factor de Necrosis Tumoral
/
Proteínas de Insectos
/
Caspasas
/
Proteínas Mitocondriales
Idioma:
En
Revista:
J Biol Chem
Año:
2000
Tipo del documento:
Article
País de afiliación:
Estados Unidos