A "twist box" code of p53 inactivation: twist box: p53 interaction promotes p53 degradation.
Cancer Cell
; 22(3): 404-15, 2012 Sep 11.
Article
em En
| MEDLINE
| ID: mdl-22975381
ABSTRACT
Twist proteins have been shown to contribute to cancer development and progression by impinging on different regulatory pathways, but their mechanism of action is poorly defined. By investigating the role of Twist in sarcomas, we found that Twist1 acts as a mechanism alternative to TP53 mutation and MDM2 overexpression to inactivate p53 in mesenchymal tumors. We provide evidence that Twist1 binds p53 C terminus through the Twist box. This interaction hinders key posttranslational modifications of p53 and facilitates its MDM2-mediated degradation. Our study suggests the existence of a Twist box code of p53 inactivation and provides the proof of principle that targeting the Twist boxp53 interaction might offer additional avenues for cancer treatment.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Sarcoma
/
Proteínas Nucleares
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Proteína Supressora de Tumor p53
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Proteínas Proto-Oncogênicas c-mdm2
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Proteína 1 Relacionada a Twist
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Cancer Cell
Assunto da revista:
NEOPLASIAS
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Itália