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

Oncology

Journal of Cancer Science & Therapy

Author(s): Medema RH, Kops GJ, Bos JL, Burgering BM

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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. This article was published in Nature and referenced in Journal of Cancer Science & Therapy

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