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CDK activity antagonizes Whi5, an inhibitor of G1/S transcription in yeast

Michael Costanzo1, Joy L Nishikawa, Xiaojing Tang

  • 1Department of Medical Genetics and Microbiology, University of Toronto, 1 King's College Circle, Toronto, M5S 1A8, Canada.

Cell
|June 24, 2004
PubMed

Insights

Cyclin-dependent kinase (CDK) activity controls cell division. In yeast, Whi5 protein inhibits G1/S transcription until CDK phosphorylation releases this block, harmonizing cell cycle control across eukaryotes.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Genetics

Background:

  • Cyclin-dependent kinase (CDK) activity drives the eukaryotic cell cycle, initiating gene expression in late G1.
  • In metazoans, CDK-phosphorylated retinoblastoma protein (Rb) activates G1/S transcription by releasing E2F.
  • A direct G1 phase target for CDK activity in yeast has been elusive.

Purpose of the Study:

  • To identify the elusive G1/S transcription regulator in yeast.
  • To elucidate the mechanism by which CDK activity controls G1/S transcription in yeast.
  • To harmonize the understanding of G1/S cell cycle control across eukaryotes.

Main Methods:

  • Investigated the role of Whi5 in G1/S transcription.
  • Utilized gene deletion and CDK activity manipulation in yeast.
  • Employed in vivo and in vitro biochemical assays to study protein interactions and localization.

Main Results:

  • Identified Whi5 as a cell size regulator that inhibits G1/S transcription.
  • Demonstrated that CDK-mediated phosphorylation dissociates Whi5 from SBF/MBF transcription factors, releasing G1/S repression.
  • Showed that Whi5 deletion accelerates the G1/S transition by bypassing upstream activators.
  • Observed Whi5 nuclear import/export regulated by CDK activity, linking cell cycle progression to transcriptional repression.

Conclusions:

  • Whi5 acts as a crucial inhibitor of G1/S transcription in yeast.
  • CDK-dependent phosphorylation and subsequent nuclear export of Whi5 are key events relieving G1/S repression.
  • These findings establish a conserved mechanism for G1/S cell cycle control in eukaryotes, analogous to Rb function in metazoans.

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