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p38 mitogen-activated protein kinase is the central regulator of cyclic AMP-dependent transcription of the brown fat uncoupling protein 1 gene.

Publication ,  Journal Article
Cao, W; Daniel, KW; Robidoux, J; Puigserver, P; Medvedev, AV; Bai, X; Floering, LM; Spiegelman, BM; Collins, S
Published in: Mol Cell Biol
April 2004

It is well established that catecholamine-stimulated thermogenesis in brown fat requires beta-adrenergic elevations in cyclic AMP (cAMP) to increase expression of the uncoupling protein 1 (UCP1) gene. However, little is known about the downstream components of the signaling cascade or the relevant transcription factor targets thereof. Here we demonstrate that cAMP- and protein kinase A-dependent activation of p38 mitogen-activated protein kinase (MAPK) in brown adipocytes is an indispensable step in the transcription of the UCP1 gene in mice. By phosphorylating activating transcription factor 2 (ATF-2) and peroxisome proliferator-activated receptor gamma (PPARgamma) coativator 1alpha (PGC-1alpha), members of two distinct nuclear factor families, p38 MAPK controls the expression of the UCP1 gene through their respective interactions with a cAMP response element and a PPAR response element that both reside within a critical enhancer motif of the UCP1 gene. Activation of ATF-2 by p38 MAPK additionally serves as the cAMP sensor that increases expression of the PGC-1alpha gene itself in brown adipose tissue. In conclusion, our findings illustrate that by orchestrating the activity of multiple transcription factors, p38 MAPK is a central mediator of the cAMP signaling mechanism of brown fat that promotes thermogenesis.

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Published In

Mol Cell Biol

DOI

ISSN

0270-7306

Publication Date

April 2004

Volume

24

Issue

7

Start / End Page

3057 / 3067

Location

United States

Related Subject Headings

  • p38 Mitogen-Activated Protein Kinases
  • Uncoupling Protein 1
  • Uncoupling Agents
  • Transcription, Genetic
  • Transcription Factors
  • Thermogenesis
  • Signal Transduction
  • Random Allocation
  • Mitogen-Activated Protein Kinases
  • Mitochondrial Proteins
 

Citation

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Cao, W., Daniel, K. W., Robidoux, J., Puigserver, P., Medvedev, A. V., Bai, X., … Collins, S. (2004). p38 mitogen-activated protein kinase is the central regulator of cyclic AMP-dependent transcription of the brown fat uncoupling protein 1 gene. Mol Cell Biol, 24(7), 3057–3067. https://doi.org/10.1128/MCB.24.7.3057-3067.2004
Cao, Wenhong, Kiefer W. Daniel, Jacques Robidoux, Pere Puigserver, Alexander V. Medvedev, Xu Bai, Lisa M. Floering, Bruce M. Spiegelman, and Sheila Collins. “p38 mitogen-activated protein kinase is the central regulator of cyclic AMP-dependent transcription of the brown fat uncoupling protein 1 gene.Mol Cell Biol 24, no. 7 (April 2004): 3057–67. https://doi.org/10.1128/MCB.24.7.3057-3067.2004.
Cao W, Daniel KW, Robidoux J, Puigserver P, Medvedev AV, Bai X, et al. p38 mitogen-activated protein kinase is the central regulator of cyclic AMP-dependent transcription of the brown fat uncoupling protein 1 gene. Mol Cell Biol. 2004 Apr;24(7):3057–67.
Cao, Wenhong, et al. “p38 mitogen-activated protein kinase is the central regulator of cyclic AMP-dependent transcription of the brown fat uncoupling protein 1 gene.Mol Cell Biol, vol. 24, no. 7, Apr. 2004, pp. 3057–67. Pubmed, doi:10.1128/MCB.24.7.3057-3067.2004.
Cao W, Daniel KW, Robidoux J, Puigserver P, Medvedev AV, Bai X, Floering LM, Spiegelman BM, Collins S. p38 mitogen-activated protein kinase is the central regulator of cyclic AMP-dependent transcription of the brown fat uncoupling protein 1 gene. Mol Cell Biol. 2004 Apr;24(7):3057–3067.

Published In

Mol Cell Biol

DOI

ISSN

0270-7306

Publication Date

April 2004

Volume

24

Issue

7

Start / End Page

3057 / 3067

Location

United States

Related Subject Headings

  • p38 Mitogen-Activated Protein Kinases
  • Uncoupling Protein 1
  • Uncoupling Agents
  • Transcription, Genetic
  • Transcription Factors
  • Thermogenesis
  • Signal Transduction
  • Random Allocation
  • Mitogen-Activated Protein Kinases
  • Mitochondrial Proteins