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


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2000-04

AUTHORS

René H. Medema, Geert J. P. L. Kops, Johannes L. Bos, Boudewijn M. T. Burgering

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. More... »

PAGES

782-787

Journal

TITLE

Nature

ISSUE

6779

VOLUME

404

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/35008115

DOI

http://dx.doi.org/10.1038/35008115

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1040371322

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/10783894


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