The Ras effector RASSF2 controls the PAR-4 tumor suppressor.
Mol Cell Biol
; 30(11): 2608-20, 2010 Jun.
Article
en En
| MEDLINE
| ID: mdl-20368356
RASSF2 is a novel proapoptotic effector of K-Ras. Inhibition of RASSF2 expression enhances the transforming effects of K-Ras, and epigenetic inactivation of RASSF2 is frequently detected in mutant Ras-containing primary tumors. Thus, RASSF2 is implicated as a tumor suppressor whose inactivation facilitates transformation by disconnecting apoptotic responses from Ras. The mechanism of action of RASSF2 is not known. Here we show that RASSF2 forms a direct and endogenous complex with the prostate apoptosis response protein 4 (PAR-4) tumor suppressor. This interaction is regulated by K-Ras and is essential for the full apoptotic effects of PAR-4. RASSF2 is primarily a nuclear protein, and shuttling of PAR-4 from the cytoplasm to the nucleus is essential for its function. We show that RASSF2 modulates the nuclear translocation of PAR-4 in prostate tumor cells, providing a mechanism for its biological effects. Thus, we identify the first tumor suppressor signaling pathway emanating from RASSF2, we identify a novel mode of action of a RASSF protein, and we provide an explanation for the extraordinarily high frequency of RASSF2 inactivation we have observed in primary prostate tumors.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Genes ras
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Proteínas Supresoras de Tumor
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Proteínas Reguladoras de la Apoptosis
Tipo de estudio:
Prognostic_studies
Límite:
Adult
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Aged
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Aged80
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Animals
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Mol Cell Biol
Año:
2010
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Estados Unidos