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Molecular and Cellular Biology, June 2002, p. 3663-3673, Vol. 22, No. 11
0270-7306/02/$04.00+0     DOI: 10.1128/MCB.22.11.3663-3673.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

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

Xiaolin Li and Donald P. McDonnell*

Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710

Received 11 September 2001/ Returned for modification 29 October 2001/ Accepted 7 March 2002

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 G1-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.


* Corresponding author. Mailing address: Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710. Phone: (919) 684-6035. Fax: (919) 681-7139. E-mail: donald.mcdonnell{at}duke.edu.


Molecular and Cellular Biology, June 2002, p. 3663-3673, Vol. 22, No. 11
0022-538X/02/$04.00+0     DOI: 10.1128/MCB.22.11.3663-3673.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.




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