Document Detail


The transcription factor B-Myb is maintained in an inhibited state in target cells through its interaction with the nuclear corepressors N-CoR and SMRT.
MedLine Citation:
PMID:  11997503     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The B-Myb transcription factor has been implicated in coordinating the expression of genes involved in cell cycle regulation. Although it is expressed in a ubiquitous manner, its transcriptional activity is repressed until the G(1)-S phase of the cell cycle by an unknown mechanism. In this study we used biochemical and cell-based assays to demonstrate that the nuclear receptor corepressors N-CoR and SMRT interact with B-Myb. The significance of these B-Myb-corepressor interactions was confirmed by the finding that B-Myb mutants, which were unable to bind N-CoR, exhibited constitutive transcriptional activity. It has been shown previously that phosphorylation of B-Myb by cdk2/cyclin A enhances its transcriptional activity. We have now determined that phosphorylation by cdk2/cyclin A blocks the interaction between B-Myb and N-CoR and that mutation of the corepressor binding site within B-Myb bypasses the requirement for this phosphorylation event. Cumulatively, these findings suggest that the nuclear corepressors N-CoR and SMRT serve a previously unappreciated role as regulators of B-Myb transcriptional activity.
Authors:
Xiaolin Li; Donald P McDonnell
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Molecular and cellular biology     Volume:  22     ISSN:  0270-7306     ISO Abbreviation:  Mol. Cell. Biol.     Publication Date:  2002 Jun 
Date Detail:
Created Date:  2002-05-08     Completed Date:  2002-06-06     Revised Date:  2012-06-25    
Medline Journal Info:
Nlm Unique ID:  8109087     Medline TA:  Mol Cell Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3663-73     Citation Subset:  IM    
Affiliation:
Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
CDC2-CDC28 Kinases*
Cell Cycle Proteins*
Cell Line
Cyclin A / metabolism
Cyclin-Dependent Kinase 2
Cyclin-Dependent Kinases / metabolism
DNA-Binding Proteins / antagonists & inhibitors*,  chemistry,  genetics,  metabolism*
Membrane Proteins / metabolism
Mice
Models, Biological
Mutation
Nuclear Proteins / metabolism*
Nuclear Receptor Co-Repressor 1
Nuclear Receptor Co-Repressor 2
Phosphoproteins / metabolism
Phosphorylation
Protein Structure, Tertiary
Protein-Serine-Threonine Kinases / metabolism
Proto-Oncogene Proteins c-myb / metabolism
Recombinant Fusion Proteins / chemistry,  genetics,  metabolism
Repressor Proteins / metabolism*
Trans-Activators / antagonists & inhibitors*,  chemistry,  genetics,  metabolism*
Transcription, Genetic
Grant Support
ID/Acronym/Agency:
DK50494/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Cell Cycle Proteins; 0/Cyclin A; 0/DNA-Binding Proteins; 0/Membrane Proteins; 0/Mybl2 protein, mouse; 0/Ncor1 protein, mouse; 0/Ncor2 protein, mouse; 0/Nuclear Proteins; 0/Nuclear Receptor Co-Repressor 1; 0/Nuclear Receptor Co-Repressor 2; 0/Pag1 protein, mouse; 0/Phosphoproteins; 0/Proto-Oncogene Proteins c-myb; 0/Recombinant Fusion Proteins; 0/Repressor Proteins; 0/Trans-Activators; EC 2.7.11.1/Protein-Serine-Threonine Kinases; EC 2.7.11.22/CDC2-CDC28 Kinases; EC 2.7.11.22/Cdk2 protein, mouse; EC 2.7.11.22/Cyclin-Dependent Kinase 2; EC 2.7.11.22/Cyclin-Dependent Kinases
Comments/Corrections

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