Mdm2 associates with Ras effector NORE1 to induce the degradation of oncoprotein HIPK1.
EMBO Rep
; 13(2): 163-9, 2012 Feb 01.
Article
em En
| MEDLINE
| ID: mdl-22173032
ABSTRACT
The Ras effector NORE1 is frequently silenced in primary adenocarcinomas, although the significance of this silencing for tumorigenesis is unclear. Here we show that NORE1 induces polyubiquitination and proteasomal degradation of oncoprotein HIPK1 by facilitating its interaction with the Mdm2 E3 ubiquitin ligase. Endogenous HIPK1 is stabilized in Nore1-deficient mouse embryonic fibroblasts, and depletion of HIPK1 in NORE1-silenced lung adenocarcinoma cells inhibits anchorage-independent cell growth and tumour formation in nude mice. These findings indicate that the control of HIPK1 stability by Mdm2-NORE1 has a major effect on cell behaviour, and epigenetic inactivation of NORE1 enables adenocarcinoma formation in vivo through HIPK1 stabilization.
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
Base de dados:
MEDLINE
Assunto principal:
Proteínas Serina-Treonina Quinases
/
Proteínas Oncogênicas
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Proteínas ras
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Proteínas Monoméricas de Ligação ao GTP
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Proteínas Adaptadoras de Transdução de Sinal
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Proteínas Proto-Oncogênicas c-mdm2
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Proteólise
Tipo de estudo:
Risk_factors_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
EMBO Rep
Assunto da revista:
BIOLOGIA MOLECULAR
Ano de publicação:
2012
Tipo de documento:
Article