The prolyl isomerase Pin1 affects Che-1 stability in response to apoptotic DNA damage.
J Biol Chem
; 282(27): 19685-91, 2007 Jul 06.
Article
en En
| MEDLINE
| ID: mdl-17468107
ABSTRACT
We have previously demonstrated that DNA damage leads to stabilization and accumulation of Che-1, an RNA polymerase II-binding protein that plays an important role in transcriptional activation of p53 and in maintenance of the G(2)/M checkpoint. Here we show that Che-1 is down-regulated during the apoptotic process. We found that the E3 ligase HMD2 physically and functionally interacts with Che-1 and promotes its degradation via the ubiquitin-dependent proteasomal system. Furthermore, we found that in response to apoptotic stimuli Che-1 interacts with the peptidyl-prolyl isomerase Pin1 and that conformational changes generated by Pin1 are required for Che-1/HDM2 interaction. Notably, a Che-1 mutant lacking the capacity to bind Pin1 exhibits an increased half-life and this correlates with a diminished apoptosis in response to genotoxic stress. Our results establish Che-1 as a new Pin1 and HDM2 target and confirm its important role in the cellular response to DNA damage.
Buscar en Google
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Proteínas Represoras
/
Factores de Transcripción
/
Daño del ADN
/
Apoptosis
/
Isomerasa de Peptidilprolil
/
Proteínas Reguladoras de la Apoptosis
Límite:
Animals
/
Humans
Idioma:
En
Revista:
J Biol Chem
Año:
2007
Tipo del documento:
Article
País de afiliación:
Italia