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Phosphorylation of the transcription factor PHO4 by a cyclin-CDK complex, PHO80-PHO85

A Kaffman1, I Herskowitz, R Tjian

  • 1School of Medicine, Department of Biochemistry and Biophysics, University of California at San Francisco 94143.

Science (New York, N.Y.)
|February 25, 1994
PubMed

Insights

Researchers discovered a cyclin-dependent kinase complex, PHO80-PHO85, that regulates yeast PHO5 gene transcription by phosphorylating transcription factor PHO4. This finding reveals a novel role for cyclin-cdk complexes beyond cell-cycle control.

Area of Science:

  • Molecular Biology
  • Yeast Genetics
  • Gene Regulation

Background:

  • The yeast PHO5 gene's transcription is activated by PHO2 and PHO4 transcription factors.
  • PHO5 transcription is repressed under high phosphate conditions by PHO80 and PHO85, which are thought to inactivate PHO2 and PHO4.

Purpose of the Study:

  • To investigate the mechanism by which PHO80 and PHO85 negatively regulate PHO5 transcription.
  • To characterize the interaction between PHO80 and PHO85 and their role in PHO4 regulation.

Main Methods:

  • Homology analysis of PHO80.
  • Protein-protein interaction studies between PHO80 and PHO85.
  • In vitro phosphorylation assays of PHO4 by the PHO80-PHO85 complex.

Main Results:

  • PHO80 exhibits homology to yeast cyclins.
  • PHO80 interacts with PHO85, a protein kinase related to p34cdc2/CDC28.
  • The PHO80-PHO85 complex phosphorylates PHO4.
  • PHO4 phosphorylation correlates with the negative regulation of PHO5 transcription.

Conclusions:

  • A novel cyclin-dependent kinase (CDK) complex, PHO80-PHO85, regulates gene transcription outside of cell-cycle control.
  • PHO4 is a physiologically relevant substrate for the PHO80-PHO85 CDK complex.
  • This study elucidates a new regulatory pathway for PHO5 gene expression in yeast.

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