Department of Pharmacology, School of pharmacy, Nantong University, 19 QiXiu Road, Nantong, 226001, Jiangsu, China.
Cardiovasc Drugs Ther. 2021 Aug;35(4):769-773. doi: 10.1007/s10557-021-07173-3. Epub 2021 Apr 23.
Ang II regulates RhoGDI1 stability and cell proliferation via SUMOylation. However, how Ang II regulates RhoGDI1 SUMOylation remains unknown. In this study, we focused on revealing the effects of E1 subunits (Aos1 and Uba2) on RhoGDI1 SUMOylation in HA-VSMC proliferation.
The expressions of Aos1, Uba2, and SUMO1 were suppressed by siRNA transfection. HA-VSMCs were treated with Ang II (100 nM) for 24 h. RhoGDI1 SUMOylation and ubiquitination were checked by co-immunoprecipitation. Cell proliferation was detected by EdU assay.
Uba2 or Aos1 suppression significantly inhibited Ang II-induced SUMO2/3 modification of RhoGDI1 and cell proliferation, while not affecting SUMO1 modification of RhoGDI1. In addition, Uba2 or Aos1 suppression promoted RhoGDI1 ubiquitination and degradation. These indicate that both Uba2 and Aos1 are necessary for SUMO2/3 modification of RhoGDI1 that participates in cell proliferation by regulating RhoGDI1 ubiquitination and stability. Moreover, SUMO1 suppression did not affect RhoGDI1 ubiquitination and degradation and cell proliferation in Ang II-induced VSMCs, suggesting that SUMO1 modification does not participate in RhoGDI1 stability and cell proliferation.
This study reveals the differences between SUMO2/3 and SUMO1 modification in regulating RhoGDI1 stability and Ang II-mediated cell proliferation. Schematic summary of roles of SUMO1 and SUMO2/3 modification of RhoGDI1 in regulating RhoGDI1 stability and cell proliferation in Ang II-treated HA-VSMCs.
血管紧张素 II（Ang II）通过 SUMOylation 调节 RhoGDI1 的稳定性和细胞增殖。然而，Ang II 如何调节 RhoGDI1 的 SUMOylation 尚不清楚。在这项研究中，我们专注于揭示 E1 亚基（Aos1 和 Uba2）对 Ang II 诱导的 HA-VSMC 增殖中 RhoGDI1 SUMOylation 的影响。
通过 siRNA 转染抑制 Aos1、Uba2 和 SUMO1 的表达。用 Ang II（100 nM）处理 HA-VSMCs 24 h。通过免疫共沉淀检查 RhoGDI1 SUMOylation 和泛素化。通过 EdU 测定检测细胞增殖。
Uba2 或 Aos1 的抑制显著抑制了 Ang II 诱导的 RhoGDI1 SUMO2/3 修饰和细胞增殖，而不影响 RhoGDI1 SUMO1 修饰。此外，Uba2 或 Aos1 的抑制促进了 RhoGDI1 的泛素化和降解。这表明，Uba2 和 Aos1 对于 RhoGDI1 SUMO2/3 修饰都是必需的，通过调节 RhoGDI1 的泛素化和稳定性，参与细胞增殖。此外，在 Ang II 诱导的 VSMCs 中，SUMO1 的抑制不影响 RhoGDI1 的泛素化和降解以及细胞增殖，表明 SUMO1 修饰不参与 RhoGDI1 的稳定性和细胞增殖。
本研究揭示了 SUMO2/3 和 SUMO1 修饰在调节 RhoGDI1 稳定性和 Ang II 介导的细胞增殖方面的差异。示意总结了 SUMO1 和 SUMO2/3 修饰的 RhoGDI1 在调节 Ang II 处理的 HA-VSMCs 中的 RhoGDI1 稳定性和细胞增殖中的作用。
