Document Detail


Interaction between ubiquitin-protein ligase SCFSKP2 and E2F-1 underlies the regulation of E2F-1 degradation.
MedLine Citation:
PMID:  10559858     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The transcription factor E2F-1 is important in the control of cell proliferation. Its activity must be tightly regulated in a cell-cycle-dependent manner to enable programs of gene expression to be coupled closely with cell-cycle position. Here we show that, following its accumulation in the late G1 phase of the cell cycle, E2F-1 is rapidly degraded in S/G2 phase. This event is linked to a specific interaction of E2F-1 with the F-box-containing protein p45SKP2, which is the cell-cycle-regulated component of the ubiquitin-protein ligase SCFSKP2 that recognizes substrates for this ligase. Disruption of the interaction between E2F-1 and p45SKP2 results in a reduction in ubiquitination of E2F-1 and the stabilization and accumulation of transcriptionally active E2F-1 protein. These results indicate that an SCFSKP2-dependent ubiquitination pathway may be involved in the downregulation of E2F-1 activity in the S/G2 phase of the cell cycle, and suggest a link between SCFSKP2 and cell-cycle-dependent gene control.
Authors:
A Marti; C Wirbelauer; M Scheffner; W Krek
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Nature cell biology     Volume:  1     ISSN:  1465-7392     ISO Abbreviation:  Nat. Cell Biol.     Publication Date:  1999 May 
Date Detail:
Created Date:  1999-12-07     Completed Date:  1999-12-07     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  100890575     Medline TA:  Nat Cell Biol     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  14-9     Citation Subset:  IM    
Affiliation:
Friedrich Miescher Institut, Basel, Switzerland.
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MeSH Terms
Descriptor/Qualifier:
3T3 Cells
Animals
Carrier Proteins*
Cell Cycle / physiology*
Cell Cycle Proteins / metabolism*
Cell Line
DNA-Binding Proteins*
E2F Transcription Factors
E2F1 Transcription Factor
G1 Phase
G2 Phase
Hela Cells
Homeostasis
Humans
Kinetics
Ligases / metabolism*
Mice
Retinoblastoma-Binding Protein 1
S Phase
S-Phase Kinase-Associated Proteins
Substrate Specificity
Transcription Factor DP1
Transcription Factors / metabolism*
Ubiquitin-Protein Ligases
Ubiquitins / metabolism
Chemical
Reg. No./Substance:
0/Arid4a protein, mouse; 0/Carrier Proteins; 0/Cell Cycle Proteins; 0/DNA-Binding Proteins; 0/E2F Transcription Factors; 0/E2F1 Transcription Factor; 0/E2F1 protein, human; 0/E2f1 protein, mouse; 0/Retinoblastoma-Binding Protein 1; 0/S-Phase Kinase-Associated Proteins; 0/Transcription Factor DP1; 0/Transcription Factors; 0/Ubiquitins; EC 6.-/Ligases; EC 6.3.2.19/Ubiquitin-Protein Ligases
Comments/Corrections
Comment In:
Nat Cell Biol. 1999 May;1(1):E5-7   [PMID:  10559870 ]

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


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