The synovial sarcoma translocation protein SYT-SSX2 recruits β-catenin to the nucleus andassociates with it in an active complex
The synovial sarcoma translocation protein SYT-SSX2 recruits β-catenin to the nucleus andassociates with it in an active complex
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DOI：
10.1038/sj.onc.1209413
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发表时间：
2006-06-22
期刊：
影响因子：
8
通讯作者：
Eid, J. E.
中科院分区：
文献类型：
--
作者：
Pretto, D.;Barco, R.;Eid, J. E.
β -连环蛋白在细胞中的定位是决定其作为细胞表面粘附或细胞核转录激活因子的关键介质的关键决定因素。SYT-SSX2是染色体易位t(X; 18)（p11.2; q11.2）的融合产物，发生在滑膜肉瘤（一种软组织肿瘤）中。已知SYT-SSX2与染色质重塑复合物相关，并被认为参与控制基因表达。我们报道SYT-SSX2在b-catenin调控中起直接作用。当在哺乳动物细胞中表达时，syt - ssx2诱导β -连环蛋白募集到细胞核。有趣的是，典型Wnt的已知靶基因并没有因为SYT-SSX2的表达而被激活，β -连环蛋白的核定位也没有因为通常涉及这一事件的信号通路之一而被激活。β -catenin在细胞核中的积累导致了含有SYT-SSX2和β -catenin的转录活性核复合体的形成。更重要的是，SYT-SSX2在原发滑膜肉瘤细胞中的缺失导致细胞核β -连环蛋白信号丢失，其信号活性显著降低。这些结果揭示了控制β -catenin细胞运输的新途径，并强烈表明SYT-SSX2部分通过β -catenin信号传导促进肿瘤发展。
Localization of beta-catenin in the cell is a key determinant in its decision to function as a critical mediator of cell adhesion at the surface or a transcription activator in the nucleus. SYT-SSX2 is the fusion product of the chromosomal translocation, t( X; 18)( p11.2; q11.2), which occurs in synovial sarcoma, a soft tissue tumor. SYT-SSX2 is known to associate with chromatin remodeling complexes and is proposed to be involved in controlling gene expression. We report that SYT-SSX2 plays a direct role in b-catenin regulation. When expressed in mammalian cells, SYT-SSX2-induced beta-catenin recruitment to the nucleus. Interestingly, known target genes of canonical Wnt were not activated as a result of SYT-SSX2 expression, nor was the nuclear localization of beta-catenin due to one of the signaling pathways normally implicated in this event. beta-Catenin accumulation in the nucleus led to the formation of a transcriptionally active nuclear complex that contained SYT-SSX2 and beta-catenin. More importantly, depletion of SYT-SSX2 in primary synovial sarcoma cells resulted in loss of nuclear beta-catenin signal and a significant decrease in its signaling activity. These results unravel a novel pathway in the control of beta-catenin cellular transport and strongly suggest that SYT-SSX2 contributes to tumor development, in part through beta-catenin signaling.