Fission yeast receptor of activated C kinase (RACK1) ortholog Cpc2 regulates mitotic commitment through Wee1 kinase.
In the fission yeast Schizosaccharomyces pombe, Wee1-dependent inhibitory phosphorylation of the highly conserved Cdc2/Cdk1 kinase determines the mitotic onset when cells have reached a defined size. The receptor of activated C kinase (RACK1) is a scaffolding protein strongly conserved among eukaryotes which binds to other proteins to regulate multiple processes in mammalian cells, including the modulation of cell cycle progression during G(1)/S transition. We have recently described that Cpc2, the fission yeast ortholog to RACK1, controls from the ribosome the activation of MAPK cascades and the cellular defense against oxidative stress by positively regulating the translation of specific genes whose products participate in the above processes. Intriguingly, mutants lacking Cpc2 display an increased cell size at division, suggesting the existence of a specific cell cycle defect at the G(2)/M transition. In this work we show that protein levels of Wee1 mitotic inhibitor are increased in cells devoid of Cpc2, whereas the levels of Cdr2, a Wee1 inhibitor, are down-regulated in the above mutant. On the contrary, the kinetics of G(1)/S transition was virtually identical both in control and Cpc2-less strains. Thus, our results suggest that in fission yeast Cpc2/RACK1 positively regulates from the ribosome the mitotic onset by modulating both the protein levels and the activity of Wee1. This novel mechanism of translational control of cell cycle progression might be conserved in higher eukaryotes.
Department of Genetics and Microbiology, Facultad de Biología, Universidad de Murcia, 30071 Murcia, Spain.
Andrés
A
Núñez
Alejandro
A
Franco
Teresa
T
Soto
Jero
J
Vicente
Mariano
M
Gacto
José
J
Cansado
D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000235:genetics*; D002843:Chromatin / Q000737:chemistry; D018604:Epitope Mapping; D005434:Flow Cytometry; D005656:Fungal Proteins / Q000737:chemistry*; D015966:Gene Expression Regulation, Fungal; D007700:Kinetics; D020935:MAP Kinase Signaling System; D008856:Microscopy, Fluorescence / Q000379:methods; D008938:Mitosis; D009687:Nuclear Proteins / Q000235:genetics*; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface / Q000378:metabolism*; D012270:Ribosomes / Q000378:metabolism; D012568:Schizosaccharomyces / Q000201:enzymology* / Q000502:physiology; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics*; D013696:Temperature
D018797:Cell Cycle Proteins; D002843:Chromatin; D005656:Fungal Proteins; D009687:Nuclear Proteins; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface; D029702:Schizosaccharomyces pombe Proteins; C000617313:cpc2 protein, S pombe; C068689:wee1 protein, S pombe; D011505:Protein-Tyrosine Kinases