p53 Promotes proteasome-dependent degradation of oncogenic protein HBx by transcription of MDM2.
Mol Biol Rep
; 37(6): 2935-40, 2010 Jul.
Article
em En
| MEDLINE
| ID: mdl-19842060
ABSTRACT
Hepatitis B virus X protein (HBx) is closely involved in the development of hepatocellular carcinoma (HCC). Tumor suppressor p53 was reported to induce HBx degradation and repress its oncogenic function recently, but the molecular mechanism is unknown. In this study, we attempted to identify the underlying mechanism. We found that overexpression of p53 protein reduces the level of HBx protein and shortens its half-life, however, in MDM2 knock out cells, p53 has no effects on degradation of HBx, meanwhile, overexpression of MDM2 in absence of p53 can accelerate turnover of HBx protein. These indicate that p53-mediated HBx degradation is MDM2-dependent. MDM2 interacts with HBx in vitro and in vivo but does not promote its ubiquitination. In consistent with the results above, HCC tissue samples with wild-type p53 hardly detect HBx protein, whereas, HBx always accumulate in the tissues with mutant p53. Our data provide a possible mechanism on how p53 regulate HBx stability and also a new clue for the study of p53 mutation and HCC development.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Oncogenes
/
Transcrição Gênica
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Transativadores
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Processamento de Proteína Pós-Traducional
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Proteína Supressora de Tumor p53
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Complexo de Endopeptidases do Proteassoma
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Proteínas Proto-Oncogênicas c-mdm2
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article