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Upon binding melanocortins, <jats:styled-content style=\"fixed-case\">MC<\/jats:styled-content>1R activates several signaling cascades, notably the c<jats:styled-content style=\"fixed-case\">AMP<\/jats:styled-content> pathway leading to synthesis of photoprotective eumelanin. Polymorphisms in the <jats:italic><jats:styled-content style=\"fixed-case\">MC<\/jats:styled-content>1R<\/jats:italic> gene are a major source of normal variation of human hair color and skin pigmentation, response to ultraviolet radiation (<jats:styled-content style=\"fixed-case\">UVR<\/jats:styled-content>), and skin cancer susceptibility. The identification of a surprisingly high number of <jats:italic><jats:styled-content style=\"fixed-case\">MC<\/jats:styled-content>1R<\/jats:italic> natural variants strongly associated with pigmentary phenotypes and increased skin cancer risk has prompted research on the functional properties of the wild\u2010type receptor and frequent mutant alleles. We summarize current knowledge on <jats:styled-content style=\"fixed-case\">MC<\/jats:styled-content>1R structural and functional properties, as well as on its intracellular trafficking and signaling. We also review the current knowledge about the function of <jats:styled-content style=\"fixed-case\">MC<\/jats:styled-content>1R as a skin cancer, particularly melanoma, susceptibility gene and how it modulates the response of melanocytes to <jats:styled-content style=\"fixed-case\">UVR<\/jats:styled-content>.<\/jats:p>","DOI":"10.1111\/pcmr.12257","type":"journal-article","created":{"date-parts":[[2014,5,7]],"date-time":"2014-05-07T18:27:41Z","timestamp":1399487261000},"page":"699-720","source":"Crossref","is-referenced-by-count":179,"title":["<scp>MC<\/scp>1R, the c<scp>AMP<\/scp> pathway, and the response to solar <scp>UV<\/scp>: extending the horizon beyond pigmentation"],"prefix":"10.1111","volume":"27","author":[{"given":"Jose C.","family":"Garc\u00eda\u2010Borr\u00f3n","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology School of Medicine University of Murcia Murcia Spain"},{"name":"Instituto Murciano de Investigaci\u00f3n Biom\u00e9dica 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