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Functional analysis of microphthalmia-associated transcription factor in pigment cell-specific transcription of the human tyrosinase family genes
Author(s): Yasumoto K, Yokoyama K, Takahashi K, Tomita Y, Shibahara S
Source: JOURNAL OF BIOLOGICAL CHEMISTRY    Volume: 272    Issue: 1    Pages: 503-509    Published: JAN 3 1997  
Times Cited: 162     References: 43     
Abstract: Tyrosinase, tyrosinase-related protein-1 (TRP-1), and TRP-2 are the enzymes involved in melanin biosynthesis and are preferentially expressed in pigment cells. Their human gene promoters share the 11-base pair M box containing a CATGTG motif, which was shown here to be bound in vitro by microphthalmia-associated transcription factor (MITF). Transient cotransfection analysis showed that MITF overexpression increased the expression of a reporter gene under the control of the human tyrosinase or TRP-1 gene promoter but not the TRP-2 promoter. The promoter activation caused by MITF is dependent on each CATGTG motif of the distal enhancer element, the IM box, and the initiator E box of the tyrosinase gene and the TRP-1 M box. Furthermore, a truncated MITF lacking the carboxyl-terminal 125 amino acid residues transactivated the tyrosinase promoter less efficiently than did MITF, suggesting that MIF's carboxyl terminus contains a transcriptional activation domain, but unexpectedly such a truncated MITF remarkably transactivated the TRP-2 gene promoter. These results suggest that MITF is sufficient to direct pigment cell-specific transcription of the tyrosinase and TRP-1 genes but not the TRP-2 gene.
Document Type: Article
Language: English
Addresses:
1. TOHOKU UNIV, SCH MED, DEPT APPL PHYSIOL & MOL BIOL, AOBA KU, SENDAI, MIYAGI 98077 JAPAN
2. AKITA UNIV, SCH MED, DEPT DERMATOL, AKITA 010, JAPAN
Publisher: AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814
Subject Category: Biochemistry & Molecular Biology
IDS Number: WA564
ISSN: 0021-9258
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