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EMBO J. 2005 Dec 21;24(24):4271-8. Epub 2005 Nov 24.

Regulation of G0 entry by the Pho80-Pho85 cyclin-CDK complex.

Author information

1
Department of Microbiology and Molecular Medicine, CMU, University of Geneva, Geneva, Switzerland.

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.

PMID:
16308562
PMCID:
PMC1356330
DOI:
10.1038/sj.emboj.7600889
[Indexed for MEDLINE]
Free PMC Article

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