RNF4 介导的 SUMO 靶向泛素化缓解 PARIS/ZNF746 介导的转录抑制。
RNF4-mediated SUMO-targeted ubiquitination relieves PARIS/ZNF746-mediated transcriptional repression.
机构信息
Department of Human Functional Genomics, Advanced Science Research Promotion Center, Organization for the Promotion of Regional Innovation (OPRI), Mie University, 1577 Kurima-machiya, Tsu, 514-8507, Japan.
Department of Human Functional Genomics, Advanced Science Research Promotion Center, Organization for the Promotion of Regional Innovation (OPRI), Mie University, 1577 Kurima-machiya, Tsu, 514-8507, Japan.
出版信息
Biochem Biophys Res Commun. 2020 May 21;526(1):110-116. doi: 10.1016/j.bbrc.2020.03.063. Epub 2020 Mar 17.
The transcriptional repressor PARIS, which is a substrate of the ubiquitin E3 ligase parkin, represses the expression of the transcriptional co-activator, PGC-1α. However, little is known about how its repression activity is regulated. We have previously shown that PARIS is SUMOylated, and this SUMOylation plays an important role in regulating its transcriptional repression activity. In this study, we demonstrated that PARIS SUMOylation induced its ubiquitination and subsequent proteasomal degradation, which was mediated by the SUMO-targeted ubiquitin ligase RNF4. Reporter gene assays revealed that co-expression of SUMO3 and RNF4 relieved PARIS-mediated transcriptional repression. Conversely, the SUMO E3 ligase PIASy inhibited the RNF4-mediated ubiquitination of PARIS and blocked the RNF4-mediated relief of PARIS-mediated transcriptional repression. These results suggest that RNF4 regulates PARIS ubiquitination to control its transcriptional repression activity.
转录抑制剂 PARIS 是泛素 E3 连接酶 parkin 的底物，可抑制转录共激活因子 PGC-1α 的表达。然而，其抑制活性如何调控还知之甚少。我们之前已经表明 PARIS 可发生 SUMO 化，这种 SUMO 化在调节其转录抑制活性方面发挥着重要作用。在本研究中，我们证实 PARIS SUMO 化可诱导其泛素化和随后的蛋白酶体降解，这是由 SUMO 靶向泛素连接酶 RNF4 介导的。报告基因分析表明，SUMO3 和 RNF4 的共表达可减轻 PARIS 介导的转录抑制。相反，SUMO E3 连接酶 PIASy 抑制了 RNF4 介导的 PARIS 泛素化，并阻止了 RNF4 介导的 PARIS 介导的转录抑制的缓解。这些结果表明，RNF4 通过调节 PARIS 的泛素化来控制其转录抑制活性。
Zotero 插件