Galibert M D, Yavuzer U, Dexter T J, Goding C R
Eukaryotic Transcription Laboratory, Marie Curie Research Institute, The Chart, Oxted, Surrey, RH8 OTL, United Kingdom.
J Biol Chem. 1999 Sep 17;274(38):26894-900. doi: 10.1074/jbc.274.38.26894.
Previous work has established that the melanocyte-specific tyrosinase-related protein-1 (TRP-1) promoter is regulated positively by the microphthalmia-associated transcription factor Mitf, acting through the conserved M box and negatively by the T-box factor Tbx2, which can bind two "melanocyte-specific elements" termed the MSEu and MSEi. Both the MSEu and MSEi, which share a 6-base pair GTGTGA consensus, are also recognized by a previously unidentified melanocyte-specific factor, MSF. Here we show using a combination of DNA binding assays, proteolytic clipping, and anti-Pax3 antibodies that MSF is indistinguishable from Pax3, a paired homeodomain transcription factor implicated genetically in melanocyte development and the regulation of the Mitf promoter. Consistent with Pax3 being able to bind the TRP-1 promoter, Pax3 is expressed in melanocytes and melanomas, and TRP-1 promoter activity is up-regulated by Pax3. The results identify a novel role for Pax3 in the expression of TRP-1, and the potential role of Pax3 in the melanocyte lineage is discussed.
先前的研究已经证实，黑素细胞特异性酪氨酸酶相关蛋白-1（TRP-1）启动子受小眼相关转录因子Mitf正向调控，通过保守的M框起作用；受T-box因子Tbx2负向调控，Tbx2可结合两个称为MSEu和MSEi的“黑素细胞特异性元件”。MSEu和MSEi都有一个6个碱基对的GTGTGA共有序列，它们也被一个先前未鉴定的黑素细胞特异性因子MSF识别。在这里，我们通过结合DNA结合分析、蛋白水解剪切和抗Pax3抗体表明，MSF与Pax3无法区分，Pax3是一种配对的同源结构域转录因子，在基因上与黑素细胞发育和Mitf启动子的调控有关。与Pax3能够结合TRP-1启动子一致，Pax3在黑素细胞和黑色素瘤中表达，并且TRP-1启动子活性被Pax3上调。这些结果确定了Pax3在TRP-1表达中的新作用，并讨论了Pax3在黑素细胞谱系中的潜在作用。
