Cyclin-dependent kinase 5 regulates E2F transcription factor through phosphorylation of Rb protein in neurons.
Cell Cycle
; 11(8): 1603-10, 2012 Apr 15.
Article
en En
| MEDLINE
| ID: mdl-22456337
ABSTRACT
Recent studies have shown the involvement of cyclin-dependent kinase 5 (Cdk5) in cell cycle regulation in postmitotic neurons. In this study, we demonstrate that Cdk5 and its co-activator p35 were detected in the nuclear fraction in neurons and Cdk5/p35 phosphorylated retinoblastoma (Rb) protein, a key protein controlling cell cycle re-entry. Cdk5/p35 phosphorylates Rb at the sites similar to those phosphorylated by Cdk4 and Cdk2. Furthermore, increased Cdk5 activity elevates activity of E2F transcription factor, which can trigger cell cycle re-entry, leading to neuronal cell death. A normal Cdk5 activity in neurons did not induce E2F activation, suggesting that Cdk5 does not induce cell cycle re-entry under normal conditions. Taken together, these results indicate that Cdk5 can regulate cell cycle by its ability to phosphorylate Rb. Most importantly, increased Cdk5 activity induces cell cycle re-entry, which is especially detrimental for survival of postmitotic neurons.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Proteína de Retinoblastoma
/
Quinasa 5 Dependiente de la Ciclina
/
Factores de Transcripción E2F
/
Neuronas
Límite:
Animals
Idioma:
En
Revista:
Cell Cycle
Año:
2012
Tipo del documento:
Article
País de afiliación:
Estados Unidos