SENP3 regulates the global protein turnover and the Sp1 level via antagonizing SUMO2/3-targeted ubiquitination and degradation
SENP3 regulates the global protein turnover and the Sp1 level via antagonizing SUMO2/3-targeted ubiquitination and degradation
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SENP3 通过拮抗 SUMO2/3 靶向泛素化和降解来调节整体蛋白质周转和 Sp1 水平
DOI：
10.1007/s13238-015-0216-7
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发表时间：
2016-01-01
期刊：
影响因子：
21.1
通讯作者：
Yi, Jing
中科院分区：
文献类型：
--
作者：
Wang, Ming;Sang, Jing;Yi, Jing
最近发现，苏莫化通过泛素-蛋白酶体系统作为底物降解的靶向信号。RNF4是研究最多的人类相扑靶向泛素E3连接酶。然而，相扑蛋白水解酶、SENPs和RNF4之间的关系仍然不清楚。SENP对RNF4介导的SUMO2/3靶向蛋白降解的调节例子有限。本研究调查了SENP3在与SUMO2/3靶向泛素化相关的全球蛋白质周转中的作用，并特别关注了SENP3对Sp1稳定性的调节。我们的数据表明，SENP3损害了全球泛素化图谱，并促进了许多蛋白质的积累。SP1是一种与癌症相关的转录因子，是这些蛋白质中的一员。SENP3通过拮抗SUMO2/3靶向的泛素化和RNF4介导的蛋白酶体依赖的降解来增加Sp1蛋白的水平。SENP3使SUMO2/3的解结合减弱了Sp1与RNF4的相互作用。在胃癌细胞系和来自患者和裸鼠的标本中，Sp1的水平通常与SENP3的水平平行增加。这些结果为Sp1蛋白在多种肿瘤中的丰富提供了新的解释，并揭示了SUMO2/3结合蛋白的调节，其水平可能受到SENP3和RNF4的严格控制。
SUMOylation is recently found to function as a targeting signal for the degradation of substrates through the ubiquitin-proteasome system. RNF4 is the most studied human SUMO-targeted ubiquitin E3 ligase. However, the relationship between SUMO proteases, SENPs, and RNF4 remains obscure. There are limited examples of the SENP regulation of SUMO2/3-targeted proteolysis mediated by RNF4. The present study investigated the role of SENP3 in the global protein turnover related to SUMO2/3-targeted ubiquitination and focused in particular on the SENP3 regulation of the stability of Sp1. Our data demonstrated that SENP3 impaired the global ubiquitination profile and promoted the accumulation of many proteins. Sp1, a cancer-associated transcription factor, was among these proteins. SENP3 increased the level of Sp1 protein via antagonizing the SUMO2/3-targeted ubiquitination and the consequent proteasome-dependent degradation that was mediated by RNF4. De-conjugation of SUMO2/3 by SENP3 attenuated the interaction of Sp1 with RNF4. In gastric cancer cell lines and specimens derived from patients and nude mice, the level of Sp1 was generally increased in parallel to the level of SENP3. These results provided a new explanation for the enrichment of the Sp1 protein in various cancers, and revealed a regulation of SUMO2/3 conjugated proteins whose levels may be tightly controlled by SENP3 and RNF4.