AFX-like Forkhead transcription factors mediate cell-cycle regulation by Ras and PKB through p27kip1
| Autor: | Johannes L. Bos, Boudewijn M.T. Burgering, Geert J. P. L. Kops, René H. Medema |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2000 |
| Předmět: |
Cell Cycle Proteins
Protein Serine-Threonine Kinases Biology Cell Line Geneeskunde Mice Forkhead Transcription Factors Proto-Oncogene Proteins Tumor Cells Cultured Animals Humans Caenorhabditis elegans FOXD3 Multidisciplinary Forkhead Box Protein O1 Tumor Suppressor Proteins Cell Cycle G1 Phase PTEN Phosphohydrolase Retinoblastoma protein FOXO Family 3T3 Cells Blood Proteins Molecular biology Phosphoric Monoester Hydrolases Cell biology DNA-Binding Proteins Enzyme Activation Cell Transformation Neoplastic Forkhead box L2 Gene Expression Regulation Mutation FOXO4 ras Proteins biology.protein Forkhead Box Protein O3 FOXA2 Microtubule-Associated Proteins Proto-Oncogene Proteins c-akt Cell Division Cyclin-Dependent Kinase Inhibitor p27 Signal Transduction Transcription Factors |
| Zdroj: | Nature, 404(6779), 782. Nature publishing group |
| ISSN: | 0028-0836 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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