PGC-1 coactivators regulate MITF and the tanning response.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • 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

Published Date

  • January 10, 2013

Published In

Volume / Issue

  • 49 / 1

Start / End Page

  • 145 - 157

PubMed ID

  • 23201126

Pubmed Central ID

  • 23201126

Electronic International Standard Serial Number (EISSN)

  • 1097-4164

Digital Object Identifier (DOI)

  • 10.1016/j.molcel.2012.10.027

Language

  • eng

Conference Location

  • United States