PGC-1 Coactivators Regulate MITF and the Tanning Response

Jonathan Shoag, Rizwan Haq, Mingfeng Zhang, Laura Liu, Glenn C. Rowe, Aihua Jiang, Nicole Koulisis, Caitlin Farrel, Christopher I. Amos, Qingyi Wei, Jeffrey E. Lee, Jiangwen Zhang, Thomas S. Kupper, Abrar A. Qureshi, Rutao Cui, Jiali Han, David E. Fisher, Zoltan Arany

Research output: Contribution to journalArticle

50 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)145-157
Number of pages13
JournalMolecular Cell
Volume49
Issue number1
DOIs
StatePublished - Jan 10 2013
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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    Shoag, J., Haq, R., Zhang, M., Liu, L., Rowe, G. C., Jiang, A., Koulisis, N., Farrel, C., Amos, C. I., Wei, Q., Lee, J. E., Zhang, J., Kupper, T. S., Qureshi, A. A., Cui, R., Han, J., Fisher, D. E., & Arany, Z. (2013). PGC-1 Coactivators Regulate MITF and the Tanning Response. Molecular Cell, 49(1), 145-157. https://doi.org/10.1016/j.molcel.2012.10.027