Jul 16, 2014

Melanocortins and the melanocortin 1 receptor, moving translationally towards melanoma prevention

Archives of Biochemistry and Biophysics
Zalfa A Abdel-MalekSancy Leachman

Abstract

Beginning in the last decade of the twentieth century, the fields of pigment cell research and melanoma have witnessed major breakthroughs in the understanding of the role of melanocortins in human pigmentation and the DNA damage response of human melanocytes to solar ultraviolet radiation (UV). This began with the cloning of the melanocortin 1 receptor (MC1R) gene from human melanocytes and the demonstration that the encoded receptor is functional. Subsequently, population studies found that the MC1R gene is highly polymorphic, and that some of its variants are associated with red hair phenotype, fair skin and poor tanning ability. Using human melanocytes cultured from donors with different MC1R genotypes revealed that the alleles associated with red hair color encode for a non-functional receptor. Epidemiological studies linked the MC1R red hair color variants to increased melanoma risk. Investigating the impact of different MC1R variants on the response of human melanocytes to UV led to the important discovery that the MC1R signaling activates antioxidant, DNA repair and survival pathways, in addition to stimulation of eumelanin synthesis. These effects of MC1R were absent in melanocytes expressing 2 MC1R red hair color vari...Continue Reading

Mentioned in this Paper

Malignant Neoplasm of Skin
Amphibians
Colforsin
Biochemical Pathway
Peptide Growth Factors Deficiency
Melanocyte
Biological Adaptation to Stress
H2AFX gene
MC4R gene
MC3R gene

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