Role of the ubiquitin proteasome system in regulating skin pigmentation.
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.
Ando
Hideya
H
Skin Aging and Photo-aging Research Center, Doshisha University, Kizugawa, Kyoto 619-0225, Japan.|Kobe Skin Research Institute, Kobe, Hyogo 650-0047, Japan.
Ichihashi
Masamitsu
M
Skin Aging and Photo-aging Research Center, Doshisha University, Kizugawa, Kyoto 619-0225, Japan.|Kobe Skin Research Institute, Kobe, Hyogo 650-0047, Japan.
Hearing
Vincent J
VJ
Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
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
D008543:Melanins; D046988:Proteasome Endopeptidase Complex