title: Role of the ubiquitin proteasome system in regulating skin pigmentation.
abstract: Pigmentation of the skin, hair and eyes is regulated by tyrosinase, the critical rate-limiting enzyme in melanin synthesis by melanocytes. Tyrosinase is degraded endogenously, at least in part, by the ubiquitin proteasome system (UPS). Several types of inherited hypopigmentary diseases, such as oculocutaneous albinism and Hermansky-Pudlak syndrome, involve the aberrant processing and/or trafficking of tyrosinase and its subsequent degradation which can occur due to the quality-control machinery. Studies on carbohydrate modifications have revealed that tyrosinase in the endoplasmic reticulum (ER) is proteolyzed via ER-associated protein degradation and that tyrosinase degradation can also occur following its complete maturation in the Golgi. Among intrinsic factors that regulate the UPS, fatty acids have been shown to modulate tyrosinase degradation in contrasting manners through increased or decreased amounts of ubiquitinated tyrosinase that leads to its accelerated or decelerated degradation by proteasomes.
authors.affiliation: Skin Aging and Photo-aging Research Center, Doshisha University, Kizugawa, Kyoto 619-0225, Japan.|Kobe Skin Research Institute, Kobe, Hyogo 650-0047, Japan.
authors.forename: Hideya
authors.initials: H
authors.lastname: Ando
authors.affiliation: Skin Aging and Photo-aging Research Center, Doshisha University, Kizugawa, Kyoto 619-0225, Japan.|Kobe Skin Research Institute, Kobe, Hyogo 650-0047, Japan.
authors.forename: Masamitsu
authors.initials: M
authors.lastname: Ichihashi
authors.affiliation: Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Vincent J
authors.initials: VJ
authors.lastname: Hearing
mesh_terms: D000818:Animals; D004721:Endoplasmic Reticulum / Q000201:enzymology / Q000378:metabolism; D006801:Humans; D008543:Melanins / Q000096:biosynthesis; D008544:Melanocytes / Q000378:metabolism / Q000528:radiation effects; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D012880:Skin Pigmentation / Q000502:physiology*; D014466:Ultraviolet Rays
chemical_list: D008543:Melanins; D046988:Proteasome Endopeptidase Complex