Melanocortin 1 Receptor: Structure, Function, and Regulation.
Melanocortin 1 Receptor: Structure, Function, and Regulation.
复制标题
DOI：
10.3389/fgene.2016.00095
复制
发表时间：
2016
影响因子：
3.7
通讯作者：
D'Orazio JA
中科院分区：
文献类型：
--
作者：
Wolf Horrell EM;Boulanger MC;D'Orazio JA
黑素皮质素1受体(MC1R)是一种黑素细胞Gs蛋白偶联受体，调节皮肤色素沉着、紫外线反应和黑色素瘤风险。它是一个高度多态的基因，功能的丧失与公平、紫外线敏感和黑色素瘤易感的表型相关，这是由于表皮黑化缺陷和次优DNA修复所致。CAMP信号是由正性激动剂黑素皮质素、负性激动剂刺参信号蛋白和中性拮抗剂β-防御素3控制的。cAMP信号的激活上调了黑色素的产生和在表皮中的沉积，从而限制了紫外线对皮肤的穿透，并增强了核苷酸切除修复(NER)，这是基因组稳定的途径，负责清除紫外光以避免突变。在此，我们综述了MC1R的结构和功能，并总结了我们实验室在MC1R信号影响NER的分子机制方面的发现。
The melanocortin 1 receptor (MC1R) is a melanocytic Gs protein coupled receptor that regulates skin pigmentation, UV responses, and melanoma risk. It is a highly polymorphic gene, and loss of function correlates with a fair, UV-sensitive, and melanoma-prone phenotype due to defective epidermal melanization and sub-optimal DNA repair. MC1R signaling, achieved through adenylyl cyclase activation and generation of the second messenger cAMP, is hormonally controlled by the positive agonist melanocortin, the negative agonist agouti signaling protein, and the neutral antagonist β-defensin 3. Activation of cAMP signaling up-regulates melanin production and deposition in the epidermis which functions to limit UV penetration into the skin and enhances nucleotide excision repair (NER), the genomic stability pathway responsible for clearing UV photolesions from DNA to avoid mutagenesis. Herein we review MC1R structure and function and summarize our laboratory’s findings on the molecular mechanisms by which MC1R signaling impacts NER.