v-Myc inhibits C/EBPbeta activity by preventing C/EBPbeta-induced phosphorylation of the co-activator p300.
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.
Steinmann
S
S
Institut für Biochemie, Westfälische-Wilhelms-Universität Münster, Münster, Germany.
Schulte
K
K
Beck
K
K
Chachra
S
S
Bujnicki
T
T
Klempnauer
K-H
KH
D000595:Amino Acid Sequence; D000818:Animals; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002645:Chickens; D050881:E1A-Associated p300 Protein / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D022423:Myeloid Cells / Q000378:metabolism; D016274:Oncogene Protein p55(v-myc) / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011784:Quail
D022782:CCAAT-Enhancer-Binding Protein-beta; D004791:Enzyme Inhibitors; D016274:Oncogene Protein p55(v-myc); D050881:E1A-Associated p300 Protein; D017346:Protein Serine-Threonine Kinases