| Title: |
PGC-1 Coactivators Regulate MITF and the Tanning Response |
| 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 |
| Publisher Information: |
//www.elsevier.com/locate/molcel; United States |
| Publication Year: |
2013 |
| Collection: |
University of Hong Kong: HKU Scholars Hub |
| Description: |
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. ; link_to_subscribed_fulltext |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| ISSN: |
23201126 |
| Relation: |
Molecular Cell; http://www.scopus.com/mlt/select.url?eid=2-s2.0-84872276087&selection=ref&src=s&origin=recordpage; 157; 291153; WOS:000313607300014; 145; https://hub.hku.hk/handle/10722/180756; 49 |
| DOI: |
10.1016/j.molcel.2012.10.027 |
| Availability: |
https://hub.hku.hk/handle/10722/180756; https://doi.org/10.1016/j.molcel.2012.10.027 |
| Accession Number: |
edsbas.E49512FA |
| Database: |
BASE |