UV-induced expression of key component of the tanning process, the POMC and MC1R genes, is dependent on the p-38-activated upstream stimulating factor-1 (USF-1).
Protection against UV-mediated DNA damage and the onset of oncogenesis is afforded by the tanning response in which UV irradiation triggers melanocytes to increase production of melanin that is then transferred to keratinocytes. A key component of the tanning process is the UV-mediated induction of the pro-opiomelanocortin (POMC) and MC1R genes encoding the alpha-melanocyte-stimulating hormone and its receptor, respectively, which play a crucial role in pigmentation by regulating the intracellular levels of cAMP. How these genes are regulated in response to UV irradiation is not known. Here we have shown that UV-induced activation of the POMC and MC1R promoters is mediated by p38 stress-activated kinase signaling to the transcription factor, upstream stimulating factor-1 (USF-1). Importantly, melanocytes derived from USF-1 -/- mice exhibit a defective UV response and fail to activate POMC and MC1R expression in response to UV irradiation. The results define USF-1 as a critical UV-responsive activator of genes implicated in protection from solar radiation.
Corre
Sébastien
S
CNRS UMR 6061 Laboratoire de Génétique et Développement, Faculté de Médecine, Université de Rennes-1, 2 Avenue du Pr. Léon Bernard, 35043 Rennes, France.
Primot
Aline
A
Sviderskaya
Elena
E
Bennett
Dorothy C
DC
Vaulont
Sophie
S
Goding
Colin R
CR
Galibert
Marie-Dominique
MD
D020816:Amino Acid Motifs; D000818:Animals; D015153:Blotting, Western; D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D004247:DNA / Q000378:metabolism; D004249:DNA Damage; D018076:DNA, Complementary / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D008543:Melanins / Q000378:metabolism; D008544:Melanocytes / Q000378:metabolism; D051379:Mice; D008954:Models, Biological; D010858:Pigmentation; D011333:Pro-Opiomelanocortin / Q000096:biosynthesis* / Q000235:genetics; D011401:Promoter Regions, Genetic; D012313:RNA / Q000378:metabolism; D011979:Receptors, Pituitary Hormone / Q000096:biosynthesis* / Q000235:genetics; D015398:Signal Transduction; D013053:Spectrophotometry; D013472:Sunlight; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D014162:Transfection; D019076:Transgenes; D014466:Ultraviolet Rays; D051720:Upstream Stimulatory Factors; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D008543:Melanins; D011979:Receptors, Pituitary Hormone; D014157:Transcription Factors; C497181:USF1 protein, human; D051720:Upstream Stimulatory Factors; C497183:Usf1 protein, mouse; D012313:RNA; D011333:Pro-Opiomelanocortin; C029446:MSH receptor; D004247:DNA; D008156:Luciferases; D048051:p38 Mitogen-Activated Protein Kinases