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Wolf Horrell EM, Boulanger MC, D'Orazio JA. Melanocortin 1 Receptor: Structure, Function, and Regulation. Front Genet. 2016;7:95doi: 10.3389/fgene.2016.00095.
Wolf Horrell, E. M., Boulanger, M. C., & D'Orazio, J. A. (2016). Melanocortin 1 Receptor: Structure, Function, and Regulation. Frontiers in genetics, 795. https://doi.org/10.3389/fgene.2016.00095
Wolf Horrell, Erin M, et al. "Melanocortin 1 Receptor: Structure, Function, and Regulation." Frontiers in genetics vol. 7 (2016): 95. doi: https://doi.org/10.3389/fgene.2016.00095
Wolf Horrell EM, Boulanger MC, D'Orazio JA. Melanocortin 1 Receptor: Structure, Function, and Regulation. Front Genet. 2016 May 31;7:95. doi: 10.3389/fgene.2016.00095. eCollection 2016. PMID: 27303435; PMCID: PMC4885833.
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Front Genet. 2016 May 31;7:95. doi: 10.3389/fgene.2016.00095. eCollection 2016.

Melanocortin 1 Receptor: Structure, Function, and Regulation.

Frontiers in genetics

Erin M Wolf Horrell, Mary C Boulanger, John A D'Orazio

Affiliations

  1. Department of Physiology, University of Kentucky College of Medicine Lexington, KY, USA.
  2. Markey Cancer Center, University of Kentucky College of Medicine Lexington, KY, USA.
  3. Department of Physiology, University of Kentucky College of MedicineLexington, KY, USA; Markey Cancer Center, University of Kentucky College of MedicineLexington, KY, USA; Departments of Pediatrics, Toxicology and Cancer Biology, Physiology, and Pharmacology and Nutritional Sciences, University of Kentucky College of MedicineLexington, KY, USA.

PMID: 27303435 PMCID: PMC4885833 DOI: 10.3389/fgene.2016.00095

Abstract

The melanocortin 1 receptor (MC1R) is a melanocytic Gs protein coupled receptor that regulates skin pigmentation, UV responses, and melanoma risk. It is a highly polymorphic gene, and loss of function correlates with a fair, UV-sensitive, and melanoma-prone phenotype due to defective epidermal melanization and sub-optimal DNA repair. MC1R signaling, achieved through adenylyl cyclase activation and generation of the second messenger cAMP, is hormonally controlled by the positive agonist melanocortin, the negative agonist agouti signaling protein, and the neutral antagonist β-defensin 3. Activation of cAMP signaling up-regulates melanin production and deposition in the epidermis which functions to limit UV penetration into the skin and enhances nucleotide excision repair (NER), the genomic stability pathway responsible for clearing UV photolesions from DNA to avoid mutagenesis. Herein we review MC1R structure and function and summarize our laboratory's findings on the molecular mechanisms by which MC1R signaling impacts NER.

Keywords: ASIP; ATR; DNA repair; MC1R; melanocortin; melanocyte; melanoma; βD3

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