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  • Original Article
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v-Myc inhibits C/EBPβ activity by preventing C/EBPβ-induced phosphorylation of the co-activator p300

Oncogene volume 28, pages 2446–2455 (2009)Cite this article

Abstract

Myc, a key regulator of cellular proliferation, differentiation and apoptosis, exerts its biological functions by activating or suppressing the transcription of specific sets of target genes. C/EBP transcription factors play important roles during differentiation of various cell types and have been identified as critical targets for v-Myc- and c-Myc-dependent suppression of myeloid and fat cell differentiation. Here, we have addressed the mechanism by which v-Myc suppresses the activity of C/EBPβ. We show that v-Myc is recruited to the aminoterminal domain of C/EBPβ and interferes with the cooperation of C/EBPβ and the co-activator p300 by preventing C/EBPβ-induced phosphorylation of p300. We have identified the protein kinase responsible for C/EBPβ-induced phosphorylation of p300 as homeo-domain interacting protein kinase 2 (HIPK2) and show that v-Myc displaces the kinase from the C/EBPβ-p300 complex. Overall, our findings that the modulation of the C/EBPβ-induced phosphorylation of p300 as a new mechanism of transcriptional suppression by v-Myc.

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Acknowledgements

We thank B Berkenfeld for excellent technical assistance and K Bister, D Crouch, G D'Orazi, R Eckner, T Hofmann and I Kitabayashi for plasmids, cells and antibodies. This work was supported by a grant from the DFG (KL461/12-1). KB and SC were supported by fellowships from the Graduate School of Chemistry (GSC-MS) at the University of Münster.

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  1. K Beck

    Present address: 3Current address: Division of Biological Sciences, UCSD, 9500 Gilman Drive, La Jolla, CA 92093, USA.,

  2. S Steinmann, K Schulte and K Beck: These authors contributed equally to this work.

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  1. Institut für Biochemie, Westfälische-Wilhelms-Universität Münster, Münster, Germany

    S Steinmann, K Schulte, K Beck, S Chachra, T Bujnicki & K-H Klempnauer

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  1. S Steinmann
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Correspondence to K-H Klempnauer.

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Steinmann, S., Schulte, K., Beck, K. et al. v-Myc inhibits C/EBPβ activity by preventing C/EBPβ-induced phosphorylation of the co-activator p300. Oncogene 28, 2446–2455 (2009). https://doi.org/10.1038/onc.2009.90

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