Role of Neurofibromin in Modulation of Expression of the Tyrosinase-Related Protein 2 Gene.
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概要
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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.
- 社団法人 日本生化学会の論文
著者
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YOSHIZAWA Miki
Department of Molecular Biology and Applied Physiology Tohoku University School of Medicine
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Shibahara Shigeki
Department Of Applied Physiology And Molecular Biology Tohoku University School Of Medicine
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Suzuki Hiroyuki
Department Of Animal Science Faculty Of Agriculture Hokkaido University
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TAKAHASHI Kazuhiro
Department of Analytical Medical Technology, Tohoku University School of Health Sciences
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Yasumoto Ken-ichi
Department of Applied Physiology and Molecular Biology, Tohoku University School of Medicine
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Fuse Nobuo
Department of Applied Physiology and Molecular Biology, Tohoku University School of Medicine
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Amae Shintaro
Department of Molecular Biology and Applied Phpsiology Tohohu Uniaersitq School of Medicine
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Amae Shintaro
Department of Molecular Biology and Applied Physiology, Tohoku University School of Medicine
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