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Molecular and Cellular Biology, November 2004, p. 10036-10046, Vol. 24, No. 22
0270-7306/04/$08.00+0     DOI: 10.1128/MCB.24.22.10036-10046.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

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

Aline Pic-Taylor,1,{dagger} Zoulfia Darieva,2,{dagger} Brian A. Morgan,1* and Andrew D. Sharrocks2*

Institute of Cell and Molecular Biosciences, Faculty of Medical Sciences, University of Newcastle upon Tyne, Newcastle upon Tyne,1 School of Biological Sciences, University of Manchester, Manchester, United Kingdom2

Received 7 April 2004/ Returned for modification 1 June 2004/ Accepted 13 August 2004

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.

* Corresponding author. Mailing address for Andrew D. Sharrocks: School of Biological Sciences, University of Manchester, Michael Smith Building, Oxford Rd., Manchester M13 9PT, United Kingdom. Phone: 0044-161 275 5979. Fax: 0044-161 275 5082. E-mail: a.d.sharrocks{at}man.ac.uk. Mailing address for Brian A. Morgan: Institute of Cell and Molecular Biosciences, Faculty of Medical Sciences, University of Newcastle upon Tyne, Newcastle upon Tyne NE2 4HH, United Kingdom. Phone: 0044-191 222 7694. Fax: 0044-191 222 7424. E-mail: b.a.morgan{at}ncl.ac.uk.

{dagger} A.P.-T. and Z.D. should be considered equal first authors.

Molecular and Cellular Biology, November 2004, p. 10036-10046, Vol. 24, No. 22
0022-538X/04/$08.00+0     DOI: 10.1128/MCB.24.22.10036-10046.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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