PGC-1 coactivators regulate MITF and the tanning response.
Mol Cell
; 49(1): 145-57, 2013 Jan 10.
Article
em En
| MEDLINE
| ID: mdl-23201126
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-1ß are critical components of this melanogenic system in melanocytes. α-MSH signaling strongly induces PGC-1α expression and stabilizes both PGC-1α and PGC-1ß 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-1ß 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-1ß gene that correlate with tanning ability and protection from melanoma in humans. These data identify PGC-1 coactivators as regulators of human tanning.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Cutâneas
/
Fatores de Transcrição
/
Proteínas de Transporte
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Fator de Transcrição Associado à Microftalmia
/
Bronzeado
/
Proteínas de Choque Térmico
/
Melanoma
Tipo de estudo:
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Idioma:
En
Revista:
Mol Cell
Assunto da revista:
BIOLOGIA MOLECULAR
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Estados Unidos