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Review
. 2009 Nov 20;10(10):4428-4434.
doi: 10.3390/ijms10104428.

Role of the ubiquitin proteasome system in regulating skin pigmentation

Hideya Ando  1   2 , Masamitsu Ichihashi  1   2 , Vincent J Hearing  3
Affiliations
Review

Role of the ubiquitin proteasome system in regulating skin pigmentation

Hideya Ando et al. Int J Mol Sci. .

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.

Keywords: fatty acid; melanin; melanocyte; pigmentation; skin; tyrosinase.

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Figures

Scheme 1.
Scheme 1.
Scheme depicting the processing and degradation of tyrosinase within melanocytes. After maturation in the Golgi, tyrosinase is trafficked either to melanosomes for melanin synthesis or to the degradation machinery. The proteolysis of tyrosinase is divided into two pathways, that is, one integrated into the ERAD in the UPS whereas the other is integrated into the endosomal/lysosomal degradation system. Whether mature tyrosinase that integrates into the ERAD transports back to the ER or bypasses the ER is still unknown. In addition, the intracellular location where the ubiquitination of tyrosinase occurs remains to be determined (adapted from Figure 3 of [1]).
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