Positive and negative regulation of c-Myb by cyclin D1, cyclin-dependent kinases, and p27 Kip1.
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.
Lei
Wanli
W
Department of Molecular Genetics and Microbiology, University of New Mexico, HSC, Albuquerque, NM 87131-0001, USA.
Liu
Fan
F
Ness
Scott A
SA
D000595:Amino Acid Sequence; D000818:Animals; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002645:Chickens; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism*; D051358:Cyclin-Dependent Kinase 4; D051361:Cyclin-Dependent Kinase 6; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D011485:Protein Binding; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D017434:Protein Structure, Tertiary; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020598:Proto-Oncogene Proteins c-myb / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011784:Quail; D016415:Sequence Alignment; D015533:Transcriptional Activation; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
C493961:Cdkn1b protein, mouse; D018797:Cell Cycle Proteins; D047428:Protein Kinase Inhibitors; D011518:Proto-Oncogene Proteins; D020598:Proto-Oncogene Proteins c-myb; D025521:Tumor Suppressor Proteins; D019938:Cyclin D1; D050760:Cyclin-Dependent Kinase Inhibitor p27; C495900:CDK4 protein, human; C495911:CDK6 protein, human; C495902:Cdk4 protein, mouse; C495912:Cdk6 protein, mouse; D051358:Cyclin-Dependent Kinase 4; D051361:Cyclin-Dependent Kinase 6; D018844:Cyclin-Dependent Kinases