Mdm2 controls CREB-dependent transactivation and initiation of adipocyte differentiation

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; Karsten Kristiansen

doi:10.1038/cdd.2012.15

Mdm2 controls CREB-dependent transactivation and initiation of adipocyte differentiation

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, Karsten Kristiansen

24 Citations (Scopus)

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 language	English
Journal	Cell Death and Differentiation
Volume	19
Issue number	8
Pages (from-to)	1381-1389
Number of pages	9
ISSN	1350-9047
DOIs	https://doi.org/10.1038/cdd.2012.15
Publication status	Published - Aug 2012

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Hallenborg, P., Feddersen, S., Francoz, S., Murano, I., Sundekilde, U., Petersen, R. K., Akimov, V., Olson, M. V., Lozano, G., Cinti, S., Gjertsen, B. T., Madsen, L., Marine, J-C., Blagoev, B., & Kristiansen, K. (2012). Mdm2 controls CREB-dependent transactivation and initiation of adipocyte differentiation. Cell Death and Differentiation, 19(8), 1381-1389. https://doi.org/10.1038/cdd.2012.15

Hallenborg, P, Feddersen, S, Francoz, S, Murano, I, Sundekilde, U, Petersen, RK, Akimov, V, Olson, MV, Lozano, G, Cinti, S, Gjertsen, BT, Madsen, L, Marine, J-C, Blagoev, B & Kristiansen, K 2012, 'Mdm2 controls CREB-dependent transactivation and initiation of adipocyte differentiation', Cell Death and Differentiation, vol. 19, no. 8, pp. 1381-1389. https://doi.org/10.1038/cdd.2012.15

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title = "Mdm2 controls CREB-dependent transactivation and initiation of adipocyte differentiation",

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.",

author = "Philip Hallenborg and S{\o}ren Feddersen and S. Francoz and I. Murano and Ulrik Sundekilde and Petersen, {R. K.} and Vyacheslav Akimov and M.V. Olson and G. Lozano and S. Cinti and B.T. Gjertsen and Louise Madsen and J.-C. Marine and Blagoy Blagoev and Karsten Kristiansen",

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AU - Hallenborg, Philip

AU - Feddersen, Søren

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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

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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 (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.

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 (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.

U2 - 10.1038/cdd.2012.15

DO - 10.1038/cdd.2012.15

M3 - Journal article

C2 - 22388350

SN - 1350-9047

VL - 19

SP - 1381

EP - 1389

JO - Cell Differentiation and Development

JF - Cell Differentiation and Development

IS - 8

ER -

Mdm2 controls CREB-dependent transactivation and initiation of adipocyte differentiation

Abstract

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