Suzuki H, Takahashi K, Yasumoto K, Shibahara S
Department of Applied Physiology and Molecular Biology, Tohoku University School of Medicine, Miyagi, Japan.
Biochem Biophys Res Commun. 1994 Dec 30;205(3):1984-91. doi: 10.1006/bbrc.1994.2903.
Neurofibromatosis type 1 (NF1) is a hereditary cancer syndrome, characterized by café-au-lait skin spots and multiple neurofibromas. A gene linked to NF1 encodes neurofibromin, an established function of which is to stimulate intrinsic GTPase activity of ras protein. By transiently coexpressing a neurofibromin cDNA in a melanoma cell line, we show that neurofibromin increases the expression of a reporter gene under the control of the tyrosinase gene promoter. Tyrosinase is a rate-limiting enzyme in melanin biosynthesis and is expressed only in melanin-producing cells. Functional analysis of neurofibromin cDNAs suggests that the domain related to a GTPase-activating protein is mainly responsible for this induction. These results suggest that neurofibromin functions as a regulator of melanogenesis, a process specific to the melanocytes derived from the neural crest.
1型神经纤维瘤病（NF1）是一种遗传性癌症综合征，其特征为牛奶咖啡斑和多发性神经纤维瘤。与NF1相关的一个基因编码神经纤维瘤蛋白，其已明确的功能是刺激ras蛋白的内在GTP酶活性。通过在黑色素瘤细胞系中瞬时共表达神经纤维瘤蛋白cDNA，我们发现神经纤维瘤蛋白可增加酪氨酸酶基因启动子控制下的报告基因的表达。酪氨酸酶是黑色素生物合成中的限速酶，仅在产生黑色素的细胞中表达。对神经纤维瘤蛋白cDNA的功能分析表明，与GTP酶激活蛋白相关的结构域主要负责这种诱导作用。这些结果表明，神经纤维瘤蛋白作为黑色素生成的调节因子发挥作用，黑色素生成是一种源自神经嵴的黑素细胞特有的过程。
