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

doi:10.1038/cdd.2012.15

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 journal › Article › peer-review

24 Scopus citations

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 (US)
Pages (from-to)	1381-1389
Number of pages	9
Journal	Cell death and differentiation
Volume	19
Issue number	8
DOIs	https://doi.org/10.1038/cdd.2012.15
State	Published - Aug 2012
Externally published	Yes

Keywords

CREB
Crtc2
Mdm2
adipogenesis

ASJC Scopus subject areas

Molecular Biology
Cell Biology

Access to Document

10.1038/cdd.2012.15

Cite this

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, JC, 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

@article{bd34ff2dba23492986f2b5522164ac9c,

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.",

keywords = "CREB, Crtc2, Mdm2, adipogenesis",

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

note = "Funding Information: Acknowledgements. This work was supported by the Danish Natural Science Research Council, the Villum Foundation, the Novo Nordisk Foundation, the Lundbeck Foundation and the Carlsberg Foundation. Part of the work was carried out as a part of the research program of the Danish Obesity Research Centre (DanORC). DanORC is supported by The Danish Council for Strategic Research (Grant No. 2101 06 0005).",

year = "2012",

month = aug,

doi = "10.1038/cdd.2012.15",

language = "English (US)",

volume = "19",

pages = "1381--1389",

journal = "Cell death and differentiation",

issn = "1350-9047",

publisher = "Nature Publishing Group",

number = "8",

}

TY - JOUR

T1 - Mdm2 controls CREB-dependent transactivation and initiation of adipocyte differentiation

AU - Hallenborg, P.

AU - Feddersen, S.

AU - Francoz, S.

AU - Murano, I.

AU - Sundekilde, U.

AU - Petersen, R. K.

AU - Akimov, V.

AU - Olson, M. V.

AU - Lozano, G.

AU - Cinti, S.

AU - Gjertsen, B. T.

AU - Madsen, L.

AU - Marine, J. C.

AU - Blagoev, B.

AU - Kristiansen, K.

N1 - Funding Information: Acknowledgements. This work was supported by the Danish Natural Science Research Council, the Villum Foundation, the Novo Nordisk Foundation, the Lundbeck Foundation and the Carlsberg Foundation. Part of the work was carried out as a part of the research program of the Danish Obesity Research Centre (DanORC). DanORC is supported by The Danish Council for Strategic Research (Grant No. 2101 06 0005).

PY - 2012/8

Y1 - 2012/8

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.

KW - CREB

KW - Crtc2

KW - Mdm2

KW - adipogenesis

UR - http://www.scopus.com/inward/record.url?scp=84863727020&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84863727020&partnerID=8YFLogxK

U2 - 10.1038/cdd.2012.15

DO - 10.1038/cdd.2012.15

M3 - Article

C2 - 22388350

AN - SCOPUS:84863727020

SN - 1350-9047

VL - 19

SP - 1381

EP - 1389

JO - Cell death and differentiation

JF - Cell death and differentiation

IS - 8

ER -

Mdm2 controls CREB-dependent transactivation and initiation of adipocyte differentiation

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this