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MC 1R, the c AMP pathway, and the response to solar UV: extending the horizon beyond pigmentation
Open accessAbstract
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.
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“In wild-type eumelanic subjects, α-MSH-mediated stimulation of MC1R results in activation of the associated Gs protein, which activates adenyl cyclase and increases the levels of cellular cyclic adenosine 3’,5’-monophosphate (cAMP), which is responsible for many of the effects of α-MSH, such as activation of tyrosinase (the rate-limiting enzyme in melanogenesis), tyrosinase-related protein 1 (Tyrp”
From “Fifty Shades” of Black and Red or How Carboxyl Groups Fine Tune Eumelanin and Pheomelanin Properties (2016) · cites this paper as [11]
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Metadata
- Authors
- García‐Borrón, J. C., Abdel‐Malek, Z., & Jiménez‐Cervantes, C.
- Affiliations
- Department of Biochemistry and Molecular Biology School of Medicine University of Murcia Murcia Spain
- University of Cincinnati (US)
- Instituto Murciano de Investigación Biosanitaria (ES)
- Venue
- Pigment Cell & Melanoma Research
- Publisher
- Wiley
- Published
- 2014-05-30
- Volume
- 27
- Issue
- 5
- Pages
- 699-720
- ISSN
- 1755-1471 (ISSN-L)
- 1755-148X
- PMC
- PMC4150834
- OpenAlex
- W2036734230
- Cited by
- 187
- References
- 256
- Citations by year
- 2026: 12 · 2025: 11 · 2024: 16 · 2023: 14 · 2022: 13 · 2021: 16 · 2020: 24 · 2019: 14 · 2018: 18 · 2017: 16 · 2016: 19 · 2015: 11 · 2014: 2
- FWCI
- 1.60
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Pigment Cell & Melanoma Research (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- MINECO, Spain (SAF2012-32134)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › melanin and skin pigmentation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Melanoma and MAPK Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Keywords
- MC1R, cAMP signaling, melanocyte proliferation, skin pigmentation, hair color, melanoma susceptibility, skin cancer predisposition, receptor trafficking, G protein-coupled receptor signaling
- MeSH terms
- Cyclic AMP, Alleles, Animals, DNA Damage, Humans, Ligands, Melanocytes, Melanoma, Mutation, Neoplasms, Radiation-Induced, Phenotype, Pigmentation, Polymorphism, Genetic, Protein Processing, Post-Translational, Skin Neoplasms, Skin Pigmentation, Ultraviolet Rays, Genetic Variation, Signal Transduction, Protein Structure, Tertiary, Genetic Predisposition to Disease, Gene Expression Profiling, Protein Transport, Receptor, Melanocortin, Type 1, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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