A domain necessary for the transforming activity of SnoN is required for specific DNA binding, transcriptional repression and interaction with TAFII110
A domain necessary for the transforming activity of SnoN is required for specific DNA binding, transcriptional repression and interaction with TAFII110
复制标题
DOI：
10.1038/sj.onc.1202177
复制
发表时间：
1998-11-12
期刊：
影响因子：
8
通讯作者：
Stavnezer, E
中科院分区：
文献类型：
--
作者：
Cohen, SB;Nicol, R;Stavnezer, E
SnO是SKI癌基因家族的成员，并且与SKI具有转化禽类成纤维细胞和诱导肌肉分化的能力。Ski和Sno是形成同源二聚体和异源二聚体的核蛋白，Ski激活细胞和病毒增强子的转录，并且我们已经确定了DNA结合位点（GTCTAGAC），通过该位点它抑制转录。在这项工作中，我们表明，SnoN结合这个网站，并抑制转录的报告与这个结合位点作为上游元件。在异源报告分析中使用与Gal 4-DNA结合结构域的融合，我们鉴定了SnoN中的三重阻遏结构域，SnoN阻遏结构域的107个氨基酸延伸，其包含两个亚结构域，与转化所需的Ski的最小区域密切相关。第三个子域是独特的SnoN，通过分析涉及每个子域的缺失，我们表明，子域II和III也需要DNA结合和细胞转化。我们提供了证据的转录抑制的淬火机制，其中子域II结合TAF（II）11 O。
sno is a member of the ski oncogene family and shares ski's ability to transform avian fibroblasts and induce muscle differentiation. Ski and Sno are nuclear proteins that form homodimers and heterodimers, Ski activates transcription of cellular and viral enhancers and we have identified a DNA binding site (GTCTAGAC) through which it represses transcription. In this work, we show that SnoN binds this site and represses transcription of reporters a with this binding site as an upstream element. Using fusions with the Gal4-DNA binding domain in a heterologous reporter assay, we identify a tripartite repression domain in SnoN, A 107 amino acid stretch of the SnoN repression domain, that contains two of the subdomains, is closely related to the minimal region of Ski required for transformation. The third subdomain is unique to SnoN, By analysing deletions involving each of the subdomains, we show that subdomains II and III are also required for DNA binding and cellular transformation. We provide evidence for a quenching mechanism of transcriptional repression by which subdomain II binds to TAF(II)11O.