MC1R signaling. Intracellular partners and pathophysiological implications
| Autor: | Celia Jiménez-Cervantes, Cecilia Herraiz, Conchi Olivares, José C. García-Borrón |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
DNA Repair Biology 03 medical and health sciences Paracrine signalling Animals Humans Protein Interaction Maps Molecular Biology Transcription factor Protein kinase B Melanoma Melanocortins Genetics Polymorphism Genetic integumentary system Microphthalmia-associated transcription factor Ubiquitin ligase 030104 developmental biology biology.protein Molecular Medicine Melanocytes Melanocortin Receptor Melanocortin Type 1 Melanocortin 1 receptor Signal Transduction |
| Zdroj: | Biochimica et biophysica acta. Molecular basis of disease. 1863(10 Pt) |
| ISSN: | 0925-4439 |
| Popis: | 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 PGC1α, but pleiotropic MC1R signaling also involves activation of mitogen-activated kinases and AKT. MC1R partners such as β-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. This article is part of a Special Issue entitled: Melanocortin Receptors - edited by Ya-Xiong Tao. |
| Databáze: | OpenAIRE |
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