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PGC-1 coactivators regulate MITF and the tanning response.

Publication ,  Journal Article
Shoag, J; Haq, R; Zhang, M; Liu, L; Rowe, GC; Jiang, A; Koulisis, N; Farrel, C; Amos, CI; Wei, Q; Lee, JE; Zhang, J; Kupper, TS; Qureshi, AA ...
Published in: Mol Cell
January 10, 2013

The production of pigment by melanocytes tans the skin and protects against skin cancers. UV-exposed keratinocytes secrete α-MSH, which then activates melanin formation in melanocytes by inducing the microphthalmia-associated transcription factor (MITF). We show that PPAR-γ coactivator (PGC)-1α and PGC-1β are critical components of this melanogenic system in melanocytes. α-MSH signaling strongly induces PGC-1α expression and stabilizes both PGC-1α and PGC-1β proteins. The PGC-1s in turn activate the MITF promoter, and their expression correlates strongly with that of MITF in human melanoma cell lines and biopsy specimens. Inhibition of PGC-1α and PGC-1β blocks the α-MSH-mediated induction of MITF and melanogenic genes. Conversely, overexpression of PGC-1α induces pigment formation in cell culture and transgenic animals. Finally, polymorphism studies reveal expression quantitative trait loci in the PGC-1β gene that correlate with tanning ability and protection from melanoma in humans. These data identify PGC-1 coactivators as regulators of human tanning.

Duke Scholars

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Published In

Mol Cell

DOI

EISSN

1097-4164

Publication Date

January 10, 2013

Volume

49

Issue

1

Start / End Page

145 / 157

Location

United States

Related Subject Headings

  • alpha-MSH
  • Transcriptional Activation
  • Transcription Factors
  • Suntan
  • Skin Neoplasms
  • RNA-Binding Proteins
  • Protein Stability
  • Promoter Regions, Genetic
  • Polymorphism, Single Nucleotide
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
 

Citation

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Shoag, J., Haq, R., Zhang, M., Liu, L., Rowe, G. C., Jiang, A., … Arany, Z. (2013). PGC-1 coactivators regulate MITF and the tanning response. Mol Cell, 49(1), 145–157. https://doi.org/10.1016/j.molcel.2012.10.027
Shoag, Jonathan, Rizwan Haq, Mingfeng Zhang, Laura Liu, Glenn C. Rowe, Aihua Jiang, Nicole Koulisis, et al. “PGC-1 coactivators regulate MITF and the tanning response.Mol Cell 49, no. 1 (January 10, 2013): 145–57. https://doi.org/10.1016/j.molcel.2012.10.027.
Shoag J, Haq R, Zhang M, Liu L, Rowe GC, Jiang A, et al. PGC-1 coactivators regulate MITF and the tanning response. Mol Cell. 2013 Jan 10;49(1):145–57.
Shoag, Jonathan, et al. “PGC-1 coactivators regulate MITF and the tanning response.Mol Cell, vol. 49, no. 1, Jan. 2013, pp. 145–57. Pubmed, doi:10.1016/j.molcel.2012.10.027.
Shoag J, Haq R, Zhang M, Liu L, Rowe GC, Jiang A, Koulisis N, Farrel C, Amos CI, Wei Q, Lee JE, Zhang J, Kupper TS, Qureshi AA, Cui R, Han J, Fisher DE, Arany Z. PGC-1 coactivators regulate MITF and the tanning response. Mol Cell. 2013 Jan 10;49(1):145–157.
Journal cover image

Published In

Mol Cell

DOI

EISSN

1097-4164

Publication Date

January 10, 2013

Volume

49

Issue

1

Start / End Page

145 / 157

Location

United States

Related Subject Headings

  • alpha-MSH
  • Transcriptional Activation
  • Transcription Factors
  • Suntan
  • Skin Neoplasms
  • RNA-Binding Proteins
  • Protein Stability
  • Promoter Regions, Genetic
  • Polymorphism, Single Nucleotide
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha