MC1R, Eumelanin and Pheomelanin: Their Role in Determining the Susceptibility to Skin Cancer

Abstract

Skin pigmentation is due to the accumulation of two types of melanin granules in the keratinocytes. Besides being the most potent blocker of ultraviolet radiation (UVR), the role of melanin in photo-protection is complex. This is because one type of melanin called eumelanin is UV absorbent whereas the other, pheomelanin, is photo-unstable and may even promote carcinogenesis. Skin hyperpigmentation may be caused by stress or exposure to sunlight, which stimulates the release of α-melanocyte stimulating hormone (α-MSH) from damaged keratinocytes. Melanocortin 1 receptor (MC1R) is a key signaling molecule on melanocytes that responds to α-MSH by inducing expression of enzymes responsible for eumelanin synthesis. Persons with red hair have mutations in the MC1R causing its inactivation; this leads to a paucity of eumelanin production and makes red-heads more susceptible to skin cancer. Apart from its effects on melanin production, the α-MSH/MC1R signaling is also a potent anti-inflammatory pathway and has been shown to promote anti-melanoma immunity. This review will focus on the role of MC1R in terms of its regulation of melanogenesis and influence on the immune system with respect to skin cancer susceptibility.

A Study of the Whitening Activities of Magnolia obovata Bark Ethyl Acetate Fractions as Cosmetic Ingredient

“…멜라닌은 자색에서 검은색을 띄는 eumelanin과 황색 에서 적색을 띄는 pheomelanin 두 종류가 있으며, 표피 의 기저층에 존재하는 멜라닌 세포에 의해 생산되고 주변 keratinocyte로 전이되어 피부색을 나타낸다 [1][2][3]. 멜라닌 자극 호르몬(melanocyte stimulating hormones, α-MSH)이 멜라닌 자극 호르몬 수용체(melanocortin-1 receptor, MC1-R)와 결합하여 [4] adenylyl cyclase를 활 성화 시키게 되고, cyclic adenosine monophosphate (cAMP) 수준이 증가하게 되면 cAMP-dependent kinase (PKA)가 cAMP response element binding protein (CREB)을 인산화 시켜 melanocyte 특이적인 microphthalmia associated transcription factor (MITF) promoter 를 활성화 시킨다 [5][6][7][8].…”

MC1R gene variants involvement in human OCA phenotype

“…The well-known frequent MC1R strong variants are R151C, R160W and D294H whereas D84E and R142H are rare variants. The weaker RHC variants include V60L, V92M and R163Q [31]. A variant N281S is pseudoallele of MC1R.…”

“…The melanocyte-stimulating hormone receptor has an extracellular N terminus, seven transmembrane helices with a series of intracellular and extracellular loops in between and intracellular C-terminus or cytosolic tail [31]. The highly conserved cysteine residues usually present at the N-terminus of melanocortin-1 receptor are usually synthesis.…”

“…The highly conserved cysteine residues usually present at the N-terminus of melanocortin-1 receptor are usually synthesis. Thus, ASIP binding with MSH-R inhibits eumelanin synthesis and favors yellow/red pheomelanin synthesis [29][30][31]. However, the loss-of-function of MSH-R due to sequence variations in the MC1R gene may affect the ability to generate cAMP after stimulation with αMSH that results in minimal production of eumelanin in the melanocytes [32].…”

Coptis chinensis inhibits melanogenesis increasing miR-340-mediated suppression of microphathalmia-associated transcription factor

“…In addition, α-MSH induces melanogenesis by increasing intracellular cAMP levels and membrane expression of the melanocortin-1 receptor (MC1R) (Videira et al 2013). Therefore, modulation of intracellular signal transduction by α-MSH is recognized as an important target for the control of melanogenesis (Nasti and Timares 2015). Multiple studies report effective skin-whitening effects of treatments that modulate MITF expression, and although the melanogenic gene tyrosinases, TRP-1 and TRP-2, have been implicated, control of tyrosinase activity and expression did not affect melanogenesis in isolation.…”