title: MC1R, the cAMP pathway, and the response to solar UV: extending the horizon beyond pigmentation.
abstract: The melanocortin 1 receptor (MC1R) is a G protein-coupled receptor crucial for the regulation of melanocyte proliferation and function. Upon binding melanocortins, MC1R activates several signaling cascades, notably the cAMP pathway leading to synthesis of photoprotective eumelanin. Polymorphisms in the MC1R gene are a major source of normal variation of human hair color and skin pigmentation, response to ultraviolet radiation (UVR), and skin cancer susceptibility. The identification of a surprisingly high number of MC1R natural variants strongly associated with pigmentary phenotypes and increased skin cancer risk has prompted research on the functional properties of the wild-type receptor and frequent mutant alleles. We summarize current knowledge on MC1R structural and functional properties, as well as on its intracellular trafficking and signaling. We also review the current knowledge about the function of MC1R as a skin cancer, particularly melanoma, susceptibility gene and how it modulates the response of melanocytes to UVR.
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Medicine, University of Murcia, Murcia, Spain; Instituto Murciano de Investigación Biomédica (IMIB), El Palmar, Murcia, Spain.
authors.forename: Jose C
authors.initials: JC
authors.lastname: García-Borrón
authors.forename: Zalfa
authors.initials: Z
authors.lastname: Abdel-Malek
authors.forename: Celia
authors.initials: C
authors.lastname: Jiménez-Cervantes
mesh_terms: D000483:Alleles; D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism*; D004249:DNA Damage; D020869:Gene Expression Profiling; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D008024:Ligands; D008544:Melanocytes / Q000166:cytology*; D008545:Melanoma / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009154:Mutation; D009381:Neoplasms, Radiation-Induced / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D010858:Pigmentation / Q000502:physiology*; D011110:Polymorphism, Genetic; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D044102:Receptor, Melanocortin, Type 1 / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction; D012878:Skin Neoplasms / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D012880:Skin Pigmentation; D014466:Ultraviolet Rays / Q000009:adverse effects*
chemical_list: D008024:Ligands; D044102:Receptor, Melanocortin, Type 1; D000242:Cyclic AMP
keywords: MC1R variants; Melanocortin 1 receptor; cAMP; melanocytes; melanoma; ultraviolet radiation