| First Author | Shoag J | Year | 2013 |
| Journal | Mol Cell | Volume | 49 |
| Issue | 1 | Pages | 145-57 |
| PubMed ID | 23201126 | Mgi Jnum | J:194191 |
| Mgi Id | MGI:5471182 | Doi | 10.1016/j.molcel.2012.10.027 |
| Citation | Shoag J, et al. (2013) PGC-1 coactivators regulate MITF and the tanning response. Mol Cell 49(1):145-57 |
| abstractText | The production of pigment by melanocytes tans the skin and protects against skin cancers. UV-exposed keratinocytes secrete alpha-MSH, which then activates melanin formation in melanocytes by inducing the microphthalmia-associated transcription factor (MITF). We show that PPAR-gamma coactivator (PGC)-1alpha and PGC-1beta are critical components of this melanogenic system in melanocytes. alpha-MSH signaling strongly induces PGC-1alpha expression and stabilizes both PGC-1alpha and PGC-1beta 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-1alpha and PGC-1beta blocks the alpha-MSH-mediated induction of MITF and melanogenic genes. Conversely, overexpression of PGC-1alpha induces pigment formation in cell culture and transgenic animals. Finally, polymorphism studies reveal expression quantitative trait loci in the PGC-1beta gene that correlate with tanning ability and protection from melanoma in humans. These data identify PGC-1 coactivators as regulators of human tanning. |
