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- Title
AFX-like Forkhead transcription factors mediate cell-cycle regulation by Ras and PKB through p27kip1.
- Authors
Medema, R H; Kops, G J; Bos, J L; Burgering, B M
- 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.
- Publication
Nature, 2000, Vol 404, Issue 6779, p782
- ISSN
0028-0836
- Publication type
Journal Article
- DOI
10.1038/35008115