Regulation of G0 entry by the Pho80-Pho85 cyclin-CDK complex.
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.
Wanke
Valeria
V
Department of Microbiology and Molecular Medicine, CMU, University of Geneva, Geneva, Switzerland.
Pedruzzi
Ivo
I
Cameroni
Elisabetta
E
Dubouloz
Frédérique
F
De Virgilio
Claudio
C
D048948:14-3-3 Proteins / Q000378:metabolism; D021581:Active Transport, Cell Nucleus; D001665:Binding Sites; D002467:Cell Nucleus / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D018844:Cyclin-Dependent Kinases / Q000737:chemistry / Q000378:metabolism*; D016213:Cyclins / Q000737:chemistry* / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000378:metabolism; D015151:Immunoblotting; D047468:Immunoprecipitation; D008954:Models, Biological; D009154:Mutation; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism; D010957:Plasmids / Q000378:metabolism; D011485:Protein Binding; D011494:Protein Kinases / Q000378:metabolism; D017434:Protein Structure, Tertiary; D012097:Repressor Proteins / Q000737:chemistry*; D016192:Resting Phase, Cell Cycle; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000378:metabolism; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases; D013997:Time Factors
D048948:14-3-3 Proteins; D017868:Cyclic AMP-Dependent Protein Kinases; D018844:Cyclin-Dependent Kinases; D016213:Cyclins; D005982:Glutathione Transferase; D049452:Green Fluorescent Proteins; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor); D011494:Protein Kinases; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D058570:TOR Serine-Threonine Kinases; C066824:PHO80 protein, S cerevisiae; C410736:Rim15 protein, S cerevisiae; C083324:TOR1 protein, S cerevisiae; C058605:PHO85 protein, S cerevisiae