Induction of cullin 7 by DNA damage attenuates p53 function.
Proc Natl Acad Sci U S A
; 104(27): 11388-93, 2007 Jul 03.
Article
em En
| MEDLINE
| ID: mdl-17586686
ABSTRACT
The p53 tumor suppressor gene encodes a transcription factor, which is translationally and posttranslationally activated after DNA damage. In a proteomic screen for p53 interactors, we found that the cullin protein Cul7 efficiently associates with p53. After DNA damage, the level of Cul7 protein increased in a caffeine-sensitive, but p53-independent, manner. Down-regulation of Cul7 by conditional microRNA expression augmented p53-mediated inhibition of cell cycle progression. Ectopic expression of Cul7 inhibited activation of p53 by DNA damaging agents and sensitized cells to adriamycin. Although Cul7 recruited the F-box protein FBX29 to p53, the combined expression of Cul7/FBX29 did not promote ubiquitination and degradation of p53 in vivo. Therefore, the inhibition of p53 activity by Cul7 is presumably mediated by alternative mechanisms. The interplay between p53 and Cul7 resembles the negative feedback loop described for p53 and Mdm2. Pharmacological modulation of Cul7 function may allow the sensitization of cancer cells expressing wild-type p53 to genotoxic agents used in cancer therapy.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Dano ao DNA
/
Proteína Supressora de Tumor p53
/
Proteínas Culina
Limite:
Humans
Idioma:
En
Revista:
Proc Natl Acad Sci U S A
Ano de publicação:
2007
Tipo de documento:
Article
País de afiliação:
Alemanha