Regulation of Cell Cycle-Specific Gene Expression through Cyclin-Dependent Kinase-Mediated Phosphorylation of the Forkhead Transcription Factor Fkh2p

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.

We thank Anne Clancy and June Saunders for excellent technical assistance. We are grateful to Peter March for advice, Steve Sedgwick, David Lydall and members of our laboratories for comments on the manuscript and helpful discussions; Gustav Ammerer for discussion of his unpublished data; and Lee Johnston, David Lydall, Richard Reece, and Uttam Surana for reagents.

This work was supported by Cancer Research UK, the BBSRC, the Wellcome Trust, and the Lister Institute of Preventive Medicine.