CDK activity antagonizes Whi5, an inhibitor of G1/S transcription in yeast.
Cyclin-dependent kinase (CDK) activity initiates the eukaryotic cell division cycle by turning on a suite of gene expression in late G1 phase. In metazoans, CDK-dependent phosphorylation of the retinoblastoma tumor suppressor protein (Rb) alleviates repression of E2F and thereby activates G1/S transcription. However, in yeast, an analogous G1 phase target of CDK activity has remained elusive. Here we show that the cell size regulator Whi5 inhibits G1/S transcription and that this inhibition is relieved by CDK-mediated phosphorylation. Deletion of WHI5 bypasses the requirement for upstream activators of the G1/S transcription factors SBF/MBF and thereby accelerates the G1/S transition. Whi5 is recruited to G1/S promoter elements via its interaction with SBF/MBF in vivo and in vitro. In late G1 phase, CDK-dependent phosphorylation dissociates Whi5 from SBF and drives Whi5 out of the nucleus. Elimination of CDK activity at the end of mitosis allows Whi5 to reenter the nucleus to again repress G1/S transcription. These findings harmonize G1/S control in eukaryotes.
Costanzo
Michael
M
Department of Medical Genetics and Microbiology, University of Toronto, 1 King's College Circle, Toronto, M5S 1A8, Canada.
Nishikawa
Joy L
JL
Tang
Xiaojing
X
Millman
Jonathan S
JS
Schub
Oliver
O
Breitkreuz
Kevin
K
Dewar
Danielle
D
Rupes
Ivan
I
Andrews
Brenda
B
Tyers
Mike
M
D000911:Antibodies, Monoclonal / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D048429:Cell Size / Q000235:genetics; D002843:Chromatin / Q000378:metabolism; D003433:Crosses, Genetic; D018844:Cyclin-Dependent Kinases / Q000378:metabolism*; D004843:Epistasis, Genetic; D016193:G1 Phase; D017353:Gene Deletion; D015966:Gene Expression Regulation, Fungal; D005800:Genes, Fungal; D005809:Genes, Regulator; D008954:Models, Biological; D010766:Phosphorylation; D011233:Precipitin Tests; D011401:Promoter Regions, Genetic; D011506:Proteins / Q000032:analysis; D012313:RNA / Q000032:analysis; D011994:Recombinant Proteins / Q000378:metabolism; D012097:Repressor Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics; D016196:S Phase; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D013379:Substrate Specificity; D014158:Transcription, Genetic
D000911:Antibodies, Monoclonal; D002843:Chromatin; D011506:Proteins; D011994:Recombinant Proteins; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D012313:RNA; D018844:Cyclin-Dependent Kinases