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

Correspondence: Professor K-H Klempnauer, Biochemistry, Institute of Biochemistry, Westfälische-Wilhelms-Universität Münster, Wilhelm-Klemm-Str. 2, D-48149, Münster, Germany. E-mail: klempna@uni-muenster.de

²These authors contributed equally to this work.

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

Received 4 November 2008; Revised 15 February 2009; Accepted 18 February 2009; Published online 18 May 2009.

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/EBP. We show that v-Myc is recruited to the aminoterminal domain of C/EBP and interferes with the cooperation of C/EBP and the co-activator p300 by preventing C/EBP-induced phosphorylation of p300. We have identified the protein kinase responsible for C/EBP-induced phosphorylation of p300 as homeo-domain interacting protein kinase 2 (HIPK2) and show that v-Myc displaces the kinase from the C/EBP-p300 complex. Overall, our findings that the modulation of the C/EBP-induced phosphorylation of p300 as a new mechanism of transcriptional suppression by v-Myc.