Document Detail


AFX-like Forkhead transcription factors mediate cell-cycle regulation by Ras and PKB through p27kip1.
MedLine Citation:
PMID:  10783894     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
R H Medema; G J Kops; J L Bos; B M Burgering
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Nature     Volume:  404     ISSN:  0028-0836     ISO Abbreviation:  Nature     Publication Date:  2000 Apr 
Date Detail:
Created Date:  2000-05-09     Completed Date:  2000-05-09     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0410462     Medline TA:  Nature     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  782-7     Citation Subset:  IM    
Affiliation:
Department of Hematology, University Medical Center, Utrecht, The Netherlands.
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MeSH Terms
Descriptor/Qualifier:
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:
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:
Nature. 2000 Apr 13;404(6779):714   [PMID:  11012331 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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