Goldman D, Sapru M K, Stewart S, Plotkin J, Libermann T A, Wasylyk B, Guan K
Mental Health Research Institute, University of Michigan, Ann Arbor, MI 48109, USA.
Biochem J. 1998 Oct 15;335 ( Pt 2)(Pt 2):267-75. doi: 10.1042/bj3350267.
An Ets transcription factor family member, GETS-1, was cloned from a goldfish retina cDNA library. GETS-1 contains a conserved Ets DNA-binding domain at its N-terminus and is most similar to ternary complex factor (TCF) serum-response-factor protein-1a (SAP-1a). GETS-1 is expressed in many tissues, but is enriched in retina and brain. As with the TCFs SAP-1a and ets-related protein (ERP), overexpression of the GETS-1 promoter suppresses nicotinic acetylcholine receptor epsilon-subunit gene expression in cultured muscle cells. A consensus Ets binding site sequence in the promoter of the epsilon-subunit gene is required for GETS-1-mediated repression. GETS-1 repressor activity is abrogated by overexpression of an activated Ras/mitogen-activated protein kinase (MAP kinase) or by mutation of Ser-405, a MAP kinase phosphorylation site in GETS-1. Fusion proteins created between GETS-1 and the Gal4 DNA-binding domain show that, like other TCFs, GETS-1 contains a C-terminal activation domain that is activated by a Ras/MAP kinase signalling cascade. Interestingly, mutation of Ser-405 located within this activation domain abrogated transcriptional activation of the fusion protein.
从金鱼视网膜cDNA文库中克隆出一种Ets转录因子家族成员GETS-1。GETS-1在其N端含有一个保守的Ets DNA结合结构域，与三元复合因子（TCF）血清反应因子蛋白-1a（SAP-1a）最为相似。GETS-1在许多组织中表达，但在视网膜和大脑中富集。与TCF的SAP-1a和ets相关蛋白（ERP）一样，GETS-1启动子的过表达会抑制培养的肌肉细胞中烟碱型乙酰胆碱受体ε亚基基因的表达。ε亚基基因启动子中的一个共有Ets结合位点序列是GETS-1介导的抑制所必需的。激活的Ras/丝裂原活化蛋白激酶（MAP激酶）的过表达或GETS-1中MAP激酶磷酸化位点Ser-405的突变可消除GETS-1的阻遏活性。GETS-1与Gal4 DNA结合结构域之间产生的融合蛋白表明，与其他TCF一样，GETS-1包含一个C端激活结构域，该结构域由Ras/MAP激酶信号级联激活。有趣的是，位于该激活结构域内的Ser-405突变消除了融合蛋白的转录激活。
