S-Palmitoylation of Tyrosinase at Cysteine500 Regulates Melanogenesis

• DOI: 10.1016/j.jid.2022.08.040
• Publication Date: 2022-09-05T06:52:07Z
• Authors: Yoko Niki; Naoko Adachi; Masaki Fukata; Yuko Fukata; Shinichiro Oku; Chieko Makino-Oka...; Seiji Takeuchi; Kazumasa Wakamatsu; Shosuke Ito; Lieve Declercq; Daniel B. Yarosh; Tomas Mammone; Chikako Nishigori; Naoaki Saito; Takehiko Ueyama
• Keywords: Palmitoylation; Melanosome; Melanocyte

Palmitoylation is a lipid modification involving the attachment of palmitic acid to cysteine residue, thereby affecting protein function. We investigated effect palmitoylation tyrosinase, rate-limiting enzyme in melanin synthesis, using human three-dimensional skin model system and melanocyte culture. The inhibitor, 2-bromopalmitate, increased content tyrosinase levels melanogenic cells by suppressing degradation. site was Cysteine500 C-terminal cytoplasmic tail tyrosinase. nonpalmitoylatable mutant, (C500A), slowly degraded less ubiquitinated than wild-type Screening for Asp-His-His-Cys (DHHC) family proteins suggested that DHHC2, 3, 7, 15 are involved palmitoylation. Knockdown or content. Determination their subcellular localization primary melanocytes revealed were localized endoplasmic reticulum, Golgi apparatus, and/or melanosomes, whereas only DHHC2 melanosomes. Immunoprecipitation showed DHHC3 predominantly bind mature immature respectively. Taken together, at 15, especially trans-Golgi apparatus melanosomes reticulum cis-Golgi regulate melanogenesis modulating levels.