Mdm2 controls CREB-dependent transactivation and initiation of adipocyte differentiation

Research output: Contribution to journalJournal articleResearchpeer-review

  • Philip Hallenborg
  • Søren Feddersen
  • S. Francoz
  • I. Murano
  • Ulrik Sundekilde
  • R. K. Petersen
  • Vyacheslav Akimov
  • M.V. Olson
  • G. Lozano
  • S. Cinti
  • B.T. Gjertsen
  • Louise Madsen
  • J.-C. Marine
  • Blagoy Blagoev
  • Kristiansen, Karsten
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 delta (C/EBP delta) expression by facilitating recruitment of the cAMP regulatory element-binding protein (CREB) coactivator, CREB-regulated transcription coactivator (Crtc2)/TORC2, to the c/ebp delta 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. Cell Death and Differentiation (2012) 19, 1381-1389; doi:10.1038/cdd.2012.15; published online 2 March 2012
Original languageEnglish
JournalCell Death and Differentiation
Issue number8
Pages (from-to)1381-1389
Number of pages9
Publication statusPublished - 2012

ID: 40903960