Role of neurofibromin in modulation of expression of the tyrosinase-related protein 2 gene

Hiroyuki Suzuki, Kazuhiro Takahashi, Ken Ichi Yasumoto, Shintaro Amae, Miki Yoshizawa, Nobuo Fuse, Shigeki Shibahara

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)

Abstract

Tyrosinase-related protein 2 (TRP-2)/DOPAchrome tautomerase is an enzyme involved in melanin biosynthesis and plays an important role in cytoprotection by preventing the production of a toxic melanin precursor, 5,6-dihydroxyindole. Neurofibromin is the protein product of a gene linked to neurofibromatosis type 1 (NF1), which is characterized by multiple neurofibromas and abnormalities in skin pigmentation. To explore the pathogenesis of NF1, we studied the role of neurofibromin in the regulation of TRP-2 gene expression. By means of transient cotransfection assays, we show that the expression of a reporter gene under the control of the TRP-2 gene promoter was increased by a neurofibromin-dependent signal through the 71-bp region (positions -415 to -345). A Lys-to-Glu substitution at position 1425 in neurofibromin abrogated this activating function. A dominant negative Ki-ras inhibitor mimics neurofibromin's function, and additively increases TRP-2 promoter activity when coexpressed with neurofibromin. Therefore, we suggest that neurofibromin is involved in the regulation of TRP-2 gene expression. Moreover, we found a single case of a glioblastoma multiforme that expresses TRP-2 mRNA but not tyrosinase mRNA, suggesting that TRP-2 may function in human neural tissues under certain conditions.

Original languageEnglish
Pages (from-to)992-998
Number of pages7
JournalJournal of biochemistry
Volume124
Issue number5
DOIs
Publication statusPublished - 1998 Nov

Keywords

  • Gene transcription
  • Melanin
  • Melanocyte
  • Neurofibromatosis
  • Tyrosinase-related protein-2

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

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