v-Myc inhibits C/EBPbeta activity by preventing C/EBPbeta-induced phosphorylation of the co-activator p300

Oncogene. 2009 Jul 2;28(26):2446-55. doi: 10.1038/onc.2009.90. Epub 2009 May 18.

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

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • CCAAT-Enhancer-Binding Protein-beta / antagonists & inhibitors*
  • CCAAT-Enhancer-Binding Protein-beta / chemistry
  • CCAAT-Enhancer-Binding Protein-beta / genetics
  • CCAAT-Enhancer-Binding Protein-beta / metabolism*
  • Cell Line
  • Chickens
  • E1A-Associated p300 Protein / metabolism*
  • Enzyme Inhibitors / metabolism*
  • Gene Expression Regulation
  • Humans
  • Mice
  • Molecular Sequence Data
  • Myeloid Cells / metabolism
  • Oncogene Protein p55(v-myc) / genetics
  • Oncogene Protein p55(v-myc) / metabolism*
  • Phosphorylation
  • Protein-Serine-Threonine Kinases / metabolism
  • Quail

Substances

  • CCAAT-Enhancer-Binding Protein-beta
  • Enzyme Inhibitors
  • Oncogene Protein p55(v-myc)
  • E1A-Associated p300 Protein
  • Protein-Serine-Threonine Kinases