Involvement of microphthalmia-associated transcription factor (MITF) in expression of human melanocortin-1 receptor (MC1R)
Involvement of microphthalmia-associated transcription factor (MITF) in expression of human melanocortin-1 receptor (MC1R)
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DOI：
10.1016/s0024-3205(02)01996-3
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发表时间：
2002-09-20
期刊：
影响因子：
6.1
通讯作者：
Moro, O
中科院分区：
文献类型：
--
作者：
Aoki, H;Moro, O
对人黑素皮质素-1受体(MC1R)启动子的核苷酸序列分析表明，在转录起始点的上游存在一个E-box(CANNTG)。CATGTG基序的存在表明MC1R基因的表达可能受碱性螺旋-环-螺旋-亮氨酸-拉链(bHLH-LZ)型转录因子的调控。小眼球相关转录因子(MITF)属于bHLH-LZ型转录因子家族，调节酪氨酸酶和色氨酸蛋白-1等黑素生成相关酶基因的转录。我们研究了MITF是否通过与黑素细胞中酪氨酸酶和Trp-1基因相同的转录机制来调节人MC1R基因的表达。为此，我们研究了编码MITF的cDNA在NIH/3T3细胞中共表达对MC1R启动子活性的影响。此外，凝胶迁移率改变分析表明，人SK-MEL-2细胞的核提取液中含有一种蛋白，该蛋白与含有CATGTG基序的MC1R启动子区域特异结合。这些结果表明，MITF不仅调节参与黑色素合成的酶的表达，而且还调节在黑素细胞功能中起关键作用的受体的表达。(C)2002 Elsevier Science Inc.保留所有权利。
Analysis of the nucleotide sequence of human melanocortin-1 receptor (MC1R) promoter indicated that an E-box (CANNTG) is present immediately upstream of the transcriptional initiation site. The presence of the CATGTG motif suggests that MC1R gene expression may be regulated by a basic helix-loop-helix-leucine-zipper (bHLH-LZ) type transcription factor. The microphthalmia-associated transcription factor (MITF), which belongs to the family of bHLH-LZ type transcription factors, regulates the transcription of melanogenesis-related enzyme genes such as the tyrosinase and TRP-1 genes. We investigated whether MITF regulates human MC1R gene expression through the same transcriptional mechanism as tyrosinase and TRP-1 genes in melanocytes. For this purpose, the effect of co-expression of cDNA encoding MITF on MC1R promoter activity-in NIH/3T3 cells was studied. MC1R promoter activity was induced to the extent of approximately 5-fold in the presence of MITE In addition, electrophoretic mobility shift assay indicated that nuclear extracts of human SK-Mel-2 cells contain a protein that binds specifically to the MC1R promoter region containing the CATGTG motif. These results suggested that MITF regulates not only the expression of enzymes involved in melanin synthesis, but also the expression of a receptor which plays an essential role in melanocyte functions. (C) 2002 Elsevier Science Inc. All rights reserved.