MC1R signaling. Intracellular partners and pathophysiological implications

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

卷:1863

Review

Garcia-Borron, Jose C.¹ 

[1] Univ Murcia, Sch Med, Dept Biochem & Mol Biol, Murcia 30120, Spain

关键词: Melanocortin 1 receptor;    Melanocytes;    Pigmentation;    Photoprotection;    Signaling;    Melanoma;   

DOI  :  10.1016/j.bbadis.2017.02.027

来源: Elsevier

【 摘 要 】

The melanocortin-1 receptor (MC1R) preferentially expressed in melanocytes is best known as a key regulator of the synthesis of epidermal melanin pigments. Its paracrine stimulation by keratinocyte-derived melanocortins also activates DNA repair pathways and antioxidant defenses to build a complex, multifaceted photoprotective response. Many MC1R actions rely on cAMP-dependent activation of two transcription factors, MITF and PGC1 alpha, but pleiotropic MC1R signaling also involves activation of mitogen-activated kinases and AKT. MC1R partners such as beta-arrestins, PTEN and the E3 ubiquitin ligase MGRN1 differentially regulate these pathways. The MC1R gene is complex and polymorphic, with frequent variants associated with skin phenotypes and increased cancer risk. We review current knowledge of signaling from canonical MC1R, its splice isoforms and natural polymorphic variants. Recently discovered intracellular targets and partners are also discussed, to highlight the diversity of mechanisms that may contribute to normal and pathological variation of pigmentation and sensitivity to solar radiation-induced damage. (C) 2017 Elsevier B.V. All rights reserved.

【 授权许可】

Free