AFX-like Forkhead transcription factors mediate cell-cycle regulation by Ras and PKB through p27kip1

René H. Medema, Geert J. P. L. Kops, Johannes L. Bos and Boudewijn M. T. Burgering ()
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René H. Medema: Jordan Laboratory G03-647
Geert J. P. L. Kops: University Medical Center
Johannes L. Bos: University Medical Center
Boudewijn M. T. Burgering: University Medical Center

Nature, 2000, vol. 404, issue 6779, 782-787

Abstract: Abstract The Forkhead transcription factors AFX, FKHR and FKHR-L1 are orthologues of DAF-16, a Forkhead factor that regulates longevity in Caenorhabditis elegans1,2,3. Here we show that overexpression of these Forkhead transcription factors causes growth suppression in a variety of cell lines, including a Ras-transformed cell line and a cell line lacking the tumour suppressor PTEN. Expression of AFX blocks cell-cycle progression at phase G1, independent of functional retinoblastoma protein (pRb) but dependent on the cell-cycle inhibitor p27kip1. Indeed, AFX transcriptionally activates p27kip1, resulting in increased protein levels. We conclude that AFX-like proteins are involved in cell-cycle regulation and that inactivation of these proteins is an important step in oncogenic transformation.

Date: 2000
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DOI: 10.1038/35008115

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