Dataset Information

MC1R, the cAMP pathway, and the response to solar UV: extending the horizon beyond pigmentation.

ABSTRACT: The melanocortin 1 receptor (MC1R) is a G protein-coupled receptor crucial for the regulation of melanocyte proliferation and function. Upon binding melanocortins, MC1R activates several signaling cascades, notably the cAMP pathway leading to synthesis of photoprotective eumelanin. Polymorphisms in the MC1R 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 MC1R 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 MC1R structural and functional properties, as well as on its intracellular trafficking and signaling. We also review the current knowledge about the function of MC1R as a skin cancer, particularly melanoma, susceptibility gene and how it modulates the response of melanocytes to UVR.

SUBMITTER: Garcia-Borron JC

PROVIDER: S-EPMC4150834 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

MC1R, the cAMP pathway, and the response to solar UV: extending the horizon beyond pigmentation.

García-Borrón Jose C JC Abdel-Malek Zalfa Z Jiménez-Cervantes Celia C

Pigment cell & melanoma research 20140530 5

The melanocortin 1 receptor (MC1R) is a G protein-coupled receptor crucial for the regulation of melanocyte proliferation and function. Upon binding melanocortins, MC1R activates several signaling cascades, notably the cAMP pathway leading to synthesis of photoprotective eumelanin. Polymorphisms in the MC1R 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 surpris ...[more]

PMID: 24807163

Similar Datasets

Project description:ObjectiveTo investigate the efficacy, potential limitations, and biological mechanisms of UV-A1 phototherapy for skin sclerosis due to collagen deposition disorders.DesignBefore-and-after trial of UV-A1 irradiation of sclerotic skin; in vivo biochemical analyses after UV-A1 irradiation of normal skin.SettingAcademic referral center.ParticipantsPatients with morphea/scleroderma or sclerodermoid graft-vs-host disease and volunteers without skin disease. Intervention Sclerotic skin was treated with high-dose (130 J/cm(2); n = 12) or medium-dose (65 J/cm(2); n = 6) UV-A1 phototherapy 3 times per week for 14 weeks; normal skin was treated with UV-A1 irradiation at various doses and frequencies, with biopsies performed afterwards.Main outcome measuresIn sclerotic skin, induration was clinically assessed using a scoring scale. In normal skin, quantitative polymerase chain reaction was used to assess antifibrotic responses, defined as decreased type I and type III procollagen and increased matrix metalloproteinase levels.ResultsIn patients with sclerotic skin treated with high-dose UV-A1 irradiation, clinical scores for induration modestly decreased. To investigate what factors prevented further improvement (ie, complete clearance), normal skin with light pigmentation was exposed to UV-A1 irradiation (70-150 J/cm(2)) and was assessed for antifibrotic responses. A single high-dose exposure (110-150 J/cm(2)) elicited substantial antifibrotic responses and induced skin darkening. This skin darkening attenuated responses to subsequent UV-A1 exposures and was dose dependent. Thus, to minimize skin darkening, additional patients with sclerotic skin were treated with medium-dose UV-A1 phototherapy, which was no less effective than high-dose therapy.ConclusionClinical responses of sclerotic skin to UV-A1 phototherapy were modest because of UV-A1-induced skin darkening, which is photoprotective and attenuates antifibrotic responses.Trial registrationclinicaltrials.gov Identifier: NCT00129415.

Dataset Information

MC1R, the cAMP pathway, and the response to solar UV: extending the horizon beyond pigmentation.

Publications

MC1R, the cAMP pathway, and the response to solar UV: extending the horizon beyond pigmentation.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets