Mdm2 controls CREB-dependent transactivation and initiation of adipocyte differentiation

P. Hallenborg, S. Feddersen, S. Francoz, I. Murano, U. Sundekilde, R. K. Petersen, V. Akimov, M. V. Olson, G. Lozano, S. Cinti, B. T. Gjertsen, L. Madsen, J. C. Marine, B. Blagoev, K. Kristiansen

Research output: Contribution to journalArticlepeer-review

Abstract

The role of the E3 ubiquitin ligase murine double minute 2 (Mdm2) in regulating the stability of the p53 tumor suppressor is well documented. By contrast, relatively little is known about p53-independent activities of Mdm2 and the role of Mdm2 in cellular differentiation. Here we report a novel role for Mdm2 in the initiation of adipocyte differentiation that is independent of its ability to regulate p53. We show that Mdm2 is required for cAMP-mediated induction of CCAAT/enhancer-binding protein (C/EBP) expression by facilitating recruitment of the cAMP regulatory element-binding protein (CREB) coactivator, CREB-regulated transcription coactivator (Crtc2)/TORC2, to the c/ebp promoter. Our findings reveal an unexpected role for Mdm2 in the regulation of CREB-dependent transactivation during the initiation of adipogenesis. As Mdm2 is able to promote adipogenesis in the myoblast cell line C2C12, it is conceivable that Mdm2 acts as a switch in cell fate determination.

Original languageEnglish (US)
Pages (from-to)1381-1389
Number of pages9
JournalCell death and differentiation
Volume19
Issue number8
DOIs
StatePublished - Aug 2012
Externally publishedYes

Keywords

  • CREB
  • Crtc2
  • Mdm2
  • adipogenesis

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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