The SYT protein involved in the t(X;18) synovial sarcoma translocation is a transcriptional activator localised in nuclear bodies
The SYT protein involved in the t(X;18) synovial sarcoma translocation is a transcriptional activator localised in nuclear bodies
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DOI：
10.1093/hmg/6.9.1559
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发表时间：
1997-09-01
影响因子：
3.5
通讯作者：
Goodwin, G
中科院分区：
文献类型：
--
作者：
Brett, D;Whitehouse, S;Goodwin, G
t（X; 18）（p11.2; q11.2）在滑膜肉瘤中发现的易位导致染色体18上的SYT基因与染色体X上的两个密切相关的基因SSX 1和SSX 2中的任一个融合。所得的嵌合基因表达SYT-SSX 1或SYT-SSX 2融合蛋白，其中SYT的C末端氨基酸被来自SSX蛋白的C末端的氨基酸替换，使用绿色荧光蛋白融合物，我们证明了SYT、SSX和SYT-SSX蛋白是核蛋白。我们证明了虽然SSX 1蛋白在细胞核中具有均匀分布，但SYT蛋白在细胞核中具有斑点分布，并且这种分布在SYT-SSX 2融合蛋白中得以保留。由于SYT斑点不与含PML的小体（POD）或剪接体共定位，因此它们可能代表一种新的核结构，表达GAL 4融合蛋白的构建体的转染证明存在于SYT-SSX融合蛋白中的SYT结构域可以激活荧光素酶报告基因的转录。18）易位导致SYT-SSX转录共激活因子的产生，其中将C末端SSX结构域添加到SYT提供了新的相互作用结构域，其将SYT激活结构域重定向到不同的靶启动子。
The t(X;18)(p11.2;q11.2) translocation found in synovial sarcomas results in the fusion of the SYT gene on chromosome 18 to either of two closely related genes SSX1 and SSX2 on chromosome X, The resulting chimaeric genes express SYT-SSX1 or SYT-SSX2 fusion proteins in which the C-terminal amino acids of SYT are replaced by amino acids from the C-terminus of the SSX proteins, Using green fluorescent protein fusions we demonstrate that the SYT, SSX and the SYT-SSX proteins are nuclear proteins,We demonstrate that whilst the SSX1 protein has a uniform nuclear distribution the SYT protein has a speckled distribution in the cell nucleus, and this distribution is retained with the SYT-SSX2 fusion protein, Since the SYT speckles do not co-localise with PML-containing bodies (PODs) or spliceosomes it is possible that they represent a novel nuclear structure, Transfection of constructs expressing GAL4 fusion proteins demonstrate that the SYT domains present in the SYT-SSX fusion proteins can activate transcription of a luciferase reporter, It is proposed that the t(X;18) translocation results in the generation of an SYT-SSX transcriptional co-activator in which the addition of the C-terminal SSX domain to SYT provides a new interacting domain that redirects the SYT activation domain to different target promoters.