CHFR is negatively regulated by SUMOylation-mediated ubiquitylation.
Biochem Biophys Res Commun
; 433(2): 194-9, 2013 Apr 05.
Article
en En
| MEDLINE
| ID: mdl-23454125
ABSTRACT
CHFR ubiquitin ligase plays an important role in cell cycle progression and tumorigenesis. CHFR tumor suppressor function is highly associated with its protein level. We recently reported that CHFR protein levels are negatively regulated by SUMOylation-mediated proteasomal degradation. In the present study, we uncover a detailed molecular mechanism how SUMOylation promotes CHFR destabilization. We demonstrate that SUMO modification of CHFR promotes its ubiquitylation and subsequent proteasomal degradation. However, SUMOylation of CHFR does not affect its auto-ubiquitylation, which generally serves as a maintenance mechanism for most ubiquitin ligases. Moreover, the E3 ubiquitin ligase activity of CHFR is dispensable for this SUMOylation-mediated ubiquitylation and degradation. Conversely, SENP2 deSUMOylating enzyme reduces SUMOylation-induced ubiquitylation of CHFR, leading to elevated CHFR protein levels. Taken together, our results present a new regulatory mechanism for CHFR that sequential post-translational modifications of CHFR by SUMO and ubiquitin coordinately regulates its stability.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Proteínas de Ciclo Celular
/
Ubiquitinación
/
Sumoilación
/
Proteínas de Neoplasias
Límite:
Humans
Idioma:
En
Revista:
Biochem Biophys Res Commun
Año:
2013
Tipo del documento:
Article