MEK kinase 1, a substrate for DEVD-directed caspases, is involved in genotoxin-induced apoptosis.
Mol Cell Biol
; 18(4): 2416-29, 1998 Apr.
Article
en En
| MEDLINE
| ID: mdl-9528810
MEK kinase 1 (MEKK1) is a 196-kDa protein that, in response to genotoxic agents, was found to undergo phosphorylation-dependent activation. The expression of kinase-inactive MEKK1 inhibited genotoxin-induced apoptosis. Following activation by genotoxins, MEKK1 was cleaved in a caspase-dependent manner into an active 91-kDa kinase fragment. Expression of MEKK1 stimulated DEVD-directed caspase activity and induced apoptosis. MEKK1 is itself a substrate for CPP32 (caspase-3). A mutant MEKK1 that is resistant to caspase cleavage was impaired in its ability to induce apoptosis. These findings demonstrate that MEKK1 contributes to the apoptotic response to genotoxins. The regulation of MEKK1 by genotoxins involves its activation, which may be part of survival pathways, followed by its cleavage, which generates a proapoptotic kinase fragment able to activate caspases. MEKK1 and caspases are predicted to be part of an amplification loop to increase caspase activity during apoptosis.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Proteínas Tirosina Quinasas
/
Cisteína Endopeptidasas
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Proteínas Serina-Treonina Quinasas
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Apoptosis
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Caspasas
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Proteínas Quinasas Activadas por Mitógenos
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Quinasa 1 de Quinasa de Quinasa MAP
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Mutágenos
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Mol Cell Biol
Año:
1998
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Estados Unidos