Regulation of G0 entry by the Pho80-Pho85 cyclin-CDK complex.
EMBO J
; 24(24): 4271-8, 2005 Dec 21.
Article
em En
| MEDLINE
| ID: mdl-16308562
ABSTRACT
Eukaryotic cell proliferation is controlled by growth factors and essential nutrients. In their absence, cells may enter into a quiescent state (G0). In Saccharomyces cerevisiae, the conserved protein kinase A (PKA) and rapamycin-sensitive TOR (TORC1) pathways antagonize G0 entry in response to carbon and/or nitrogen availability primarily by inhibiting the PAS kinase Rim15 function. Here, we show that the phosphate-sensing Pho80-Pho85 cyclin-cyclin-dependent kinase (CDK) complex also participates in Rim15 inhibition through direct phosphorylation, thereby effectively sequestering Rim15 in the cytoplasm via its association with 14-3-3 proteins. Inactivation of either Pho80-Pho85 or TORC1 causes dephosphorylation of the 14-3-3-binding site in Rim15, thus enabling nuclear import of Rim15 and induction of the Rim15-controlled G0 program. Importantly, we also show that Pho80-Pho85 and TORC1 converge on a single amino acid in Rim15. Thus, Rim15 plays a key role in G0 entry through its ability to integrate signaling from the PKA, TORC1, and Pho80-Pho85 pathways.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Repressoras
/
Fase de Repouso do Ciclo Celular
/
Ciclinas
/
Quinases Ciclina-Dependentes
/
Proteínas de Saccharomyces cerevisiae
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
EMBO J
Ano de publicação:
2005
Tipo de documento:
Article