Regulation of B-Myb activity by cyclin D1.
Evidence obtained during recent years suggests that B-Myb, a highly conserved member of the Myb transcription factor family, plays a key role in cell proliferation. We have shown previously that the activity of B-Myb is stimulated by cyclin A/Cdk2-dependent phosphorylation of the carboxyl-terminus of B-Myb. We have now investigated in more detail the effect of other cyclins on B-Myb. Here, we show that cyclin D1, in contrast to cyclin A, strongly inhibits the activity of B-Myb. This inhibitory effect does not involve increased phosphorylation of B-Myb but seems to rely on the formation of a specific complex of B-Myb and cyclin D1. Our work identifies B-Myb as an interacting partner for cyclin D1 and suggest that the activity of B-Myb during the cell cycle is controlled by the antagonistic effects of cyclin D1 and A. The results presented here suggest a more general role of cyclin D1 as regulator of transcription in addition to the known effect on RB phosphorylation.
Horstmann
S
S
Institute of Biochemistry, University of Münster, Wilhelm-Klemm-Str. 2, D-48149 Münster, Germany.
Ferrari
S
S
Klempnauer
K H
KH
D016475:3T3 Cells; D000818:Animals; D019556:COS Cells; D018797:Cell Cycle Proteins / Q000502:physiology; D002460:Cell Line; D019925:Cyclin A / Q000502:physiology; D019938:Cyclin D1 / Q000378:metabolism / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D046911:Macromolecular Substances; D051379:Mice; D015513:Oncogene Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010766:Phosphorylation; D015534:Trans-Activators / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015533:Transcriptional Activation / Q000502:physiology
D018797:Cell Cycle Proteins; D019925:Cyclin A; D004268:DNA-Binding Proteins; D046911:Macromolecular Substances; C499306:Mybl2 protein, mouse; D015513:Oncogene Proteins; D015534:Trans-Activators; D019938:Cyclin D1