Tachibana M, Takeda K, Nobukuni Y, Urabe K, Long J E, Meyers K A, Aaronson S A, Miki T
Laboratory of Molecular Genetics, National Institute on Deafness and Other Communication Disorders, NIH, Rockville, Maryland 20850, USA.
Nat Genet. 1996 Sep;14(1):50-4. doi: 10.1038/ng0996-50.
MITF (microphthalmia-associated transcription factor) encodes a transcription factor with a basic-helix-loop-helix-zipper (bHLH-Zip) motif. MITF mutations occur in patients with Waardenburg syndrome type 2, a disorder associated with melanocyte abnormalities. Here we show that ectopic expression of MITF converts NIH/3T3 fibroblasts into cells with characteristics of melanocytes. MITF transfectants formed foci of morphologically altered cells, which resemble those induced by oncogenes, but did not exhibit malignant phenotypes. Instead, they contained dendritic cells that express melanogenic marker proteins such as tyrosinase and tyrosinase-related protein 1. Most cloned cells of MITF transfectants exhibited dendritic morphology and expressed melanogenic markers, but such properties were not observed in cells transfected with closely related TFE3 cDNA. Our findings indicate that MITF is critically involved in melanocyte differentiation.
小眼畸形相关转录因子（MITF）编码一种具有碱性螺旋-环-螺旋-拉链（bHLH-Zip）基序的转录因子。MITF突变发生在2型瓦登伯格综合征患者中，该疾病与黑素细胞异常有关。在这里，我们表明MITF的异位表达将NIH/3T3成纤维细胞转化为具有黑素细胞特征的细胞。MITF转染细胞形成了形态改变的细胞集落，类似于由癌基因诱导的细胞集落，但未表现出恶性表型。相反，它们含有表达黑素生成标记蛋白如酪氨酸酶和酪氨酸酶相关蛋白1的树突状细胞。MITF转染细胞的大多数克隆细胞表现出树突状形态并表达黑素生成标记，但在用密切相关的TFE3 cDNA转染的细胞中未观察到这些特性。我们的研究结果表明，MITF在黑素细胞分化中起关键作用。
