Mdm2 controls CREB-dependent transactivation and initiation of adipocyte differentiation
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Mdm2 controls CREB-dependent transactivation and initiation of adipocyte differentiation. / Hallenborg, Philip; Feddersen, Søren; Francoz, S.; Murano, I.; Sundekilde, Ulrik; Petersen, R. K.; Akimov, Vyacheslav; Olson, M.V.; Lozano, G.; Cinti, S.; Gjertsen, B.T.; Madsen, Louise; Marine, J.-C.; Blagoev, Blagoy; Kristiansen, Karsten.
In: Cell Death and Differentiation, Vol. 19, No. 8, 2012, p. 1381-1389.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Mdm2 controls CREB-dependent transactivation and initiation of adipocyte differentiation
AU - Hallenborg, Philip
AU - Feddersen, Søren
AU - Francoz, S.
AU - Murano, I.
AU - Sundekilde, Ulrik
AU - Petersen, R. K.
AU - Akimov, Vyacheslav
AU - Olson, M.V.
AU - Lozano, G.
AU - Cinti, S.
AU - Gjertsen, B.T.
AU - Madsen, Louise
AU - Marine, J.-C.
AU - Blagoev, Blagoy
AU - Kristiansen, Karsten
PY - 2012
Y1 - 2012
N2 - 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
AB - 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
U2 - 10.1038/cdd.2012.15
DO - 10.1038/cdd.2012.15
M3 - Journal article
C2 - 22388350
VL - 19
SP - 1381
EP - 1389
JO - Cell Differentiation and Development
JF - Cell Differentiation and Development
SN - 1350-9047
IS - 8
ER -
ID: 40903960