PGC-1 Coactivators Regulate MITF and the Tanning Response

Academic Article

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. © 2013 Elsevier Inc.
  • Authors

    Digital Object Identifier (doi)

    Author List

  • Shoag J; Haq R; Zhang M; Liu L; Rowe GC; Jiang A; Koulisis N; Farrel C; Amos CI; Wei Q
  • Start Page

  • 145
  • End Page

  • 157
  • Volume

  • 49
  • Issue

  • 1