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Regulation of B-Myb activity by cyclin D1

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Abstract

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.

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Acknowledgements

We thank A Brehmer-Fastnacht, B Mutschler and D Wenning for excellent technical assistance, U Ziebold for discussions and R Weinberg for providing plasmids. This study was supported by grants from the DFG to K-H Klempnauer (K1 461/5-3 and K1 461/9-1) and to S Ferrari (Fe 387/1-1).

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Author notes

  1. Stefano Ferrari

    Present address: Department of Oncology, Novartis Pharma AG, K-125.4.01, Basel, CH-4002, Switzerland

Authors and Affiliations

  1. Institute of Biochemistry, University of Münster, Wilhelm-Klemm-Str. 2, D-48149 Münster, Germany

    Sebastian Horstmann & Karl-Heinz Klempnauer

  2. Institute for Experimental Cancer Research, Tumor Biology Center, PO Box 1120, Freiburg, D-79011, Germany

    Stefano Ferrari

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  1. Sebastian Horstmann
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  2. Stefano Ferrari
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  3. Karl-Heinz Klempnauer
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Horstmann, S., Ferrari, S. & Klempnauer, KH. Regulation of B-Myb activity by cyclin D1. Oncogene 19, 298–306 (2000). https://doi.org/10.1038/sj.onc.1203302

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