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Blood, 15 May 2005, Vol. 105, No. 10, pp. 3855-3861.
Prepublished online as a Blood First Edition Paper on February 1, 2005; DOI 10.1182/blood-2004-08-3342.


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HEMATOPOIESIS

Positive and negative regulation of c-Myb by cyclin D1, cyclin-dependent kinases, and p27 Kip1

Wanli Lei, Fan Liu, and Scott A. Ness

From the Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, Albuquerque, NM.

The c-Myb transcription factor controls differentiation and proliferation in hematopoietic and other cell types and has latent transforming activity, but little is known about its regulation during the cell cycle. Here, c-Myb was identified as part of a protein complex from human T cells containing the cyclin-dependent kinase (CDK) CDK6. Assays using model reporter constructs as well as endogenous target genes showed that the activity of c-Myb was inhibited by cyclin D1 plus CDK4 or CDK6 but stimulated by expression of the CDK inhibitors p16 Ink4a, p21 Cip1, or p27 Kip1. Mapping experiments identified a highly conserved region in c-Myb which, when transferred to the related A-Myb transcription factor, also rendered it responsive to CDKs and p27. The results suggest that c-Myb activity is directly regulated by cyclin D1 and CDKs and imply that c-Myb activity is regulated during the cell cycle in hematopoietic cells.


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