1. Positive and negative regulation of c-Myb by cyclin D1, cyclin-dependent kinases, and p27 Kip1.
- Author
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Lei W, Liu F, and Ness SA
- Subjects
- Amino Acid Sequence, Animals, Cell Cycle, Cell Cycle Proteins genetics, Cell Line, Chickens, Cyclin D1 genetics, Cyclin-Dependent Kinase 4, Cyclin-Dependent Kinase 6, Cyclin-Dependent Kinase Inhibitor p27, Cyclin-Dependent Kinases antagonists & inhibitors, Cyclin-Dependent Kinases genetics, Humans, Mice, Molecular Sequence Data, Protein Binding, Protein Kinase Inhibitors pharmacology, Protein Structure, Tertiary, Proto-Oncogene Proteins antagonists & inhibitors, Proto-Oncogene Proteins c-myb chemistry, Proto-Oncogene Proteins c-myb genetics, Quail, Sequence Alignment, Transcriptional Activation, Tumor Suppressor Proteins genetics, Cell Cycle Proteins metabolism, Cyclin D1 metabolism, Cyclin-Dependent Kinases metabolism, Proto-Oncogene Proteins metabolism, Proto-Oncogene Proteins c-myb metabolism, Tumor Suppressor Proteins metabolism
- Abstract
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.
- Published
- 2005
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