SUMO-modified nuclear cyclin D1 bypasses Ras-induced senescence.
Cell Death Differ
; 18(2): 304-14, 2011 Feb.
Article
en En
| MEDLINE
| ID: mdl-20798689
Oncogene-induced senescence represents a key tumor suppressive mechanism. Here, we show that Ras oncogene-induced senescence can be mediated by the recently identified haploinsufficient tumor suppressor apoptosis-stimulating protein of p53 (ASPP) 2 through a novel and p53/p19(Arf)/p21(waf1/cip1)-independent pathway. ASPP2 suppresses Ras-induced small ubiquitin-like modifier (SUMO)-modified nuclear cyclin D1 and inhibits retinoblastoma protein (Rb) phosphorylation. The lysine residue, K33, of cyclin D1 is a key site for this newly identified regulation. In agreement with the fact that its nuclear localization is required for its oncogenic activity, we show that nuclear cyclin D1 is far more potent than wild-type (WT) cyclin D1 in bypassing Ras-induced senescence. Thus, this study identifies SUMO modification as a positive regulator of nuclear cyclin D1, and reveals a new way by which cell cycle entry and senescence are regulated.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Senescencia Celular
/
Proteínas ras
/
Ciclina D1
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Proteínas Supresoras de Tumor
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Proteína SUMO-1
Límite:
Animals
Idioma:
En
Revista:
Cell Death Differ
Año:
2011
Tipo del documento:
Article
Pais de publicación:
Reino Unido