Long-term suppression of tyrosinase by terrein via tyrosinase degradation and its decreased expression

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Title
Long-term suppression of tyrosinase by terrein via tyrosinase degradation and its decreased expression
Author(s)
S H Park; D S Kim; H K Lee; S B Kwon; Sangku LeeIn Ja RyooWon Gon Kim; Ick Dong Yoo; K C Park
Bibliographic Citation
Experimental Dermatology, vol. 18, no. 6, pp. 562-566
Publication Year
2009
Abstract
Previously, we reported that a fungal metabolite, terrein, decreases melanin synthesis via downregulation of microphthalmia-associated transcription factor (MITF). In the present study, we further investigated the long-term hypopigmenting action of terrein in a spontaneously immortalized mouse melanocyte cell line, Mel-Ab. Treatment with terrein at a concentration of 50 μM strongly decreased melanogenesis in a time-dependent manner. Interestingly, the decreased tyrosinase protein levels lasted for at least 7 days, even though the MITF protein levels were restored after 3 days of treatment. In accordance with the results of Western blot analyses, the tyrosinase mRNA levels were found to be continuously decreased for at least 7 days, even though recovery of the MITF mRNA levels began after 3 days of terrein treatment. Therefore, we evaluated tyrosinase downregulation to determine if it is caused by proteasomal degradation. We found that the reduction in tyrosinase levels that was induced by terrein was clearly recovered by MG-132, a proteasome inhibitor. Moreover, ubiquitination of tyrosinase increased following treatment with terrein in the presence of MG-132. Taken together, these results suggest that terrein decreases melanogenesis through ubiquitin-dependent proteasomal degradation as well as via decreased expression of its mRNA.
Keyword
melanocytemelanogenesisproteasomal degradationterreintyrosinase
ISSN
0906-6705
Publisher
Wiley
DOI
http://dx.doi.org/10.1111/j.1600-0625.2009.00847.x
Type
Article
Appears in Collections:
Ochang Branch Institute > Chemical Biology Research Center > 1. Journal Articles
Division of Research on National Challenges > Infectious Disease Research Center > 1. Journal Articles
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