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The cooperation of B-Myb with the coactivator p300 is orchestrated by cyclins A and D1

Oncogene volume 23, pages 1392–1404 (2004)Cite this article

Abstract

B-Myb is a highly conserved member of the Myb family of transcription factors whose activity is regulated during the cell cycle. Previous work has shown that the activity of B-Myb is stimulated by cyclin A/Cdk2-dependent phosphorylation whereas interaction of B-Myb with cyclin D1 inhibits its activity. Here, we have investigated the role of p300 as a coactivator for B-Myb. We show that B-Myb-dependent transactivation is stimulated by p300 as a result of interaction between B-Myb and p300. We have mapped the sequences responsible for the interaction of B-Myb and p300 to the E1A-binding region of p300 and the transactivation domain of B-Myb, respectively. Furthermore, our data suggest that phosphorylation of B-Myb stimulates its acetylation by p300 and that the acetylation of B-Myb is necessary for the full stimulation of its transactivation potential by p300. We have also studied the effect of cyclin D1 on the cooperation of B-Myb and p300. Based on our results we propose that cyclin D1 inhibits the activity of B-Myb by interfering with the interaction of B-Myb and p300. The data reported here provide novel insight into the mechanisms by which the activity of B-Myb is regulated during the cell cycle. Taken together they suggest that the coactivator p300 plays an important role in this regulation and that the cooperation of B-Myb and p300 is orchestrated by cyclins A and D1.

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Acknowledgements

We thank S Ferrari and C Schwartz for valuable discussions, A Brehmer-Fastnacht and D Wenning for excellent technical assistance, A Hecht for providing the HAT-deficient p300 mutant and RE Lewis for providing B-Myb mutants. This study was supported by a grant from the DFG (KL 461/9-2) and by the Fonds der chemischen Industrie.

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  1. Sebastian Horstmann

    Present address: Institut für Biochemie, Universität Köln, Zülpicher Str. 47, D-50674, Köln, Germany

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  1. Institut für Biochemie, Westfälische-Wilhelms-Universität Münster, Wilhelm-Klemm-Str. 2, Münster, D-48149, Germany

    Stephan Schubert, Sebastian Horstmann, Thorsten Bartusel & Karl-Heinz Klempnauer

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Correspondence to Karl-Heinz Klempnauer.

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Schubert, S., Horstmann, S., Bartusel, T. et al. The cooperation of B-Myb with the coactivator p300 is orchestrated by cyclins A and D1. Oncogene 23, 1392–1404 (2004). https://doi.org/10.1038/sj.onc.1207255

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