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MC 1R, the c AMP pathway, and the response to solar UV : extending the horizon beyond pigmentation
Author(s) -
GarcíaBorrón Jose C.,
AbdelMalek Zalfa,
JiménezCervantes Celia
Publication year - 2014
Publication title -
pigment cell and melanoma research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.618
H-Index - 105
eISSN - 1755-148X
pISSN - 1755-1471
DOI - 10.1111/pcmr.12257
Subject(s) - chemistry , biology , microbiology and biotechnology
Summary The melanocortin 1 receptor ( MC 1R) is a G protein‐coupled receptor crucial for the regulation of melanocyte proliferation and function. Upon binding melanocortins, MC 1R activates several signaling cascades, notably the c AMP pathway leading to synthesis of photoprotective eumelanin. Polymorphisms in the MC 1R 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 MC 1R 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 MC 1R structural and functional properties, as well as on its intracellular trafficking and signaling. We also review the current knowledge about the function of MC 1R as a skin cancer, particularly melanoma, susceptibility gene and how it modulates the response of melanocytes to UVR .