Regulation of cell cycle-specific gene expression through cyclin-dependent kinase-mediated phosphorylation of the forkhead transcription factor Fkh2p

Mol Cell Biol. 2004 Nov;24(22):10036-46. doi: 10.1128/MCB.24.22.10036-10046.2004.

Abstract

The forkhead transcription factor Fkh2p acts in a DNA-bound complex with Mcm1p and the coactivator Ndd1p to regulate cell cycle-dependent expression of the CLB2 gene cluster in Saccharomyces cerevisiae. Here, we demonstrate that Fkh2p is a target of cyclin-dependent protein kinases and that phosphorylation of Fkh2p promotes interactions between Fkh2p and the coactivator Ndd1p. These phosphorylation-dependent changes in the Fkh2p-Ndd1p complex play an important role in the cell cycle-regulated expression of the CLB2 cluster. Our data therefore identify an important regulatory target for cyclin-dependent kinases in the cell cycle and further our molecular understanding of the key cell cycle regulatory transcription factor Fkh2p.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • CDC28 Protein Kinase, S cerevisiae / genetics
  • CDC28 Protein Kinase, S cerevisiae / metabolism
  • Cell Cycle
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Cyclin B / genetics
  • Cyclin B / metabolism
  • Cyclin-Dependent Kinases / genetics
  • Cyclin-Dependent Kinases / metabolism*
  • Forkhead Transcription Factors
  • Gene Expression Regulation, Fungal
  • Genes, Fungal
  • Macromolecular Substances
  • Models, Biological
  • Multigene Family
  • Mutagenesis
  • Phosphorylation
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Saccharomyces cerevisiae / cytology
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*

Substances

  • CLB2 protein, S cerevisiae
  • Cell Cycle Proteins
  • Cyclin B
  • Fkh2 protein, S cerevisiae
  • Forkhead Transcription Factors
  • Macromolecular Substances
  • NDD1 protein, S cerevisiae
  • Recombinant Fusion Proteins
  • Saccharomyces cerevisiae Proteins
  • Transcription Factors
  • CDC28 Protein Kinase, S cerevisiae
  • Cyclin-Dependent Kinases