Intracellular composition of fatty acid affects the processing and function of tyrosinase through the ubiquitin-proteasome pathway

Hideya Ando, Zhi Ming Wen, Hee Yong Kim, Julio C. Valencia, Gertrude E. Costin, Hidenori Watabe, Ken Ichi Yasumoto, Yoko Niki, Hirofumi Kondoh, Masamitsu Ichihashi, Vincent J. Hearing

Research output: Contribution to journalArticlepeer-review

45 Citations (Scopus)

Abstract

Proteasomes are multicatalytic proteinase complexes within cells that selectively degrade ubiquitinated proteins. We have recently demonstrated that fatty acids, major components of cell membranes, are able to regulate the proteasomal degradation of tyrosinase, a critical enzyme required for melanin biosynthesis, in contrasting manners by relative increases or decreases in the ubiquitinated tyrosinase. In the present study, we show that altering the intracellular composition of fatty acids affects the post-Golgi degradation of tyrosinase. Incubation with linoleic acid (C18:2) dramatically changed the fatty acid composition of cultured B16 melanoma cells, i.e. the remarkable increase in polyunsaturated fatty acids such as linoleic acid and arachidonic acid (C20:4) was compensated by the decrease in monounsaturated fatty acids such as oleic acid (C18:1) and palmitoleic acid (C16:1), with little effect on the proportion of saturated to unsaturated fatty acid. When the composition of intracellular fatty acids was altered, tyrosinase was rapidly processed to the Golgi apparatus from the ER (endoplasmic reticulum) and the degradation of tyrosinase was increased after its maturation in the Golgi. Retention of tyrosinase in the ER was observed when cells were treated with linoleic acid in the presence of proteasome inhibitors, explaining why melanin synthesis was decreased in cells treated with linoleic acid and a proteasome inhibitor despite the abrogation of tyrosinase degradation. These results suggest that the intracellular composition of fatty acid affects the processing and function of tyrosinase in connection with the ubiquitin-proteasome pathway and suggest that this might be a common physiological approach to regulate protein degradation.

Original languageEnglish
Pages (from-to)43-50
Number of pages8
JournalBiochemical Journal
Volume394
Issue number1
DOIs
Publication statusPublished - 2006 Feb 15
Externally publishedYes

Keywords

  • Fatty acid composition
  • Linoleic acid
  • Melanin
  • Palmitic acid
  • Tyrosinase
  • Ubiquitin-proteasome pathway

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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