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Nature. 2000 Apr 13;404(6779):782-7.

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

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  • 1Department of Hematology, University Medical Center, Utrecht, The Netherlands.

Abstract

The Forkhead transcription factors AFX, FKHR and FKHR-L1 are orthologues of DAF-16, a Forkhead factor that regulates longevity in Caenorhabditis elegans. 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.

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PMID:
10783894
[PubMed - indexed for MEDLINE]
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