| AFX-like Forkhead transcription factors mediate cell-cycle regulation by Ras and PKB through p27kip1. | |
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MedLine Citation:
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PMID: 10783894 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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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Authors:
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R H Medema; G J Kops; J L Bos; B M Burgering |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Nature Volume: 404 ISSN: 0028-0836 ISO Abbreviation: Nature Publication Date: 2000 Apr |
Date Detail:
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Created Date: 2000-05-09 Completed Date: 2000-05-09 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 0410462 Medline TA: Nature Country: ENGLAND |
Other Details:
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Languages: eng Pagination: 782-7 Citation Subset: IM |
Affiliation:
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Department of Hematology, University Medical Center, Utrecht, The Netherlands. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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3T3 Cells Animals Blood Proteins / genetics, physiology* Caenorhabditis elegans Cell Cycle / physiology* Cell Cycle Proteins* Cell Division Cell Line Cell Transformation, Neoplastic Cyclin-Dependent Kinase Inhibitor p27 DNA-Binding Proteins / metabolism Enzyme Activation Forkhead Transcription Factors G1 Phase / physiology Gene Expression Regulation Humans Mice Microtubule-Associated Proteins / genetics, metabolism* Mutation PTEN Phosphohydrolase Phosphoric Monoester Hydrolases / genetics, metabolism Protein-Serine-Threonine Kinases* Proto-Oncogene Proteins / metabolism* Proto-Oncogene Proteins c-akt Signal Transduction Transcription Factors / genetics, metabolism, physiology* Tumor Cells, Cultured Tumor Suppressor Proteins* ras Proteins / metabolism* |
| Chemical | |
Reg. No./Substance:
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0/Blood Proteins; 0/Cdkn1b protein, mouse; 0/Cell Cycle Proteins; 0/DNA-Binding Proteins; 0/FOXO1 protein, human; 0/FOXO4 protein, human; 0/Forkhead Transcription Factors; 0/Foxo1 protein, mouse; 0/Microtubule-Associated Proteins; 0/Proto-Oncogene Proteins; 0/Transcription Factors; 0/Tumor Suppressor Proteins; 147604-94-2/Cyclin-Dependent Kinase Inhibitor p27; EC 2.7.11.1/Protein-Serine-Threonine Kinases; EC 2.7.11.1/Proto-Oncogene Proteins c-akt; EC 3.1.3.-/Phosphoric Monoester Hydrolases; EC 3.1.3.48/PTEN protein, human; EC 3.1.3.67/PTEN Phosphohydrolase; EC 3.6.5.2/ras Proteins |
| Comments/Corrections | |
Comment In:
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Nature. 2000 Apr 13;404(6779):714
[PMID:
11012331
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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