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

Zalfa A. Abdel-Malek, Viki B. Swope, Renny J. Starner, Leonid Koikov, Pamela Cassidy, Sancy Leachman

Research output: Contribution to journalArticle

27 Citations (Scopus)

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 variants that result in loss of function of the receptor. The importance of the MC1R in reducing UV-induced genotoxicity in melanocytes led us to design small peptide analogs of the physiological MC1R agonist α-melanocortin (α-melanocyte stimulating hormone; α-MSH) for the goal of utilizing them for melanoma chemoprevention.

Original languageEnglish (US)
Pages (from-to)4-12
Number of pages9
JournalArchives of Biochemistry and Biophysics
Volume563
DOIs
StatePublished - Dec 15 2014

Fingerprint

Receptor, Melanocortin, Type 1
Melanocortins
Melanoma
Melanocytes
Hair Color
Ultraviolet radiation
Melanocyte-Stimulating Hormones
Radiation
Color
Genes
Tanning
Cloning
DNA
Chemoprevention
Pigmentation
Solar radiation
Pigments
DNA Repair
Hair
DNA Damage

Keywords

  • DNA damage
  • DNA repair
  • Human melanocytes
  • Melanocortin 1 receptor
  • Melanocortin analogs
  • Melanocortins
  • Melanoma
  • Ultraviolet radiation

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology
  • Medicine(all)

Cite this

Melanocortins and the melanocortin 1 receptor, moving translationally towards melanoma prevention. / Abdel-Malek, Zalfa A.; Swope, Viki B.; Starner, Renny J.; Koikov, Leonid; Cassidy, Pamela; Leachman, Sancy.

In: Archives of Biochemistry and Biophysics, Vol. 563, 15.12.2014, p. 4-12.

Research output: Contribution to journalArticle

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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 variants that result in loss of function of the receptor. The importance of the MC1R in reducing UV-induced genotoxicity in melanocytes led us to design small peptide analogs of the physiological MC1R agonist α-melanocortin (α-melanocyte stimulating hormone; α-MSH) for the goal of utilizing them for melanoma chemoprevention.",
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