期刊
CARDIOVASCULAR DRUGS AND THERAPY
卷 35, 期 4, 页码 769-773出版社
SPRINGER
DOI: 10.1007/s10557-021-07173-3
关键词
RhoGDI1; SUMO; E1 activating enzyme; VSMC proliferation
资金
- National Natural Sciences Foundation of China [81970226]
- Key University Science Research Project of Jiangsu Province [19KJA320010]
- Postgraduate Research & Practice Innovation Program of Jiangsu Province [KYCX19_2085]
- Research project of Nantong Health Committee [QA2020006]
This study revealed that Uba2 or Aos1 suppression significantly inhibited Ang II-induced SUMO2/3 modification of RhoGDI1 and cell proliferation, while not affecting SUMO1 modification. Additionally, Uba2 or Aos1 suppression promoted RhoGDI1 ubiquitination and degradation. These findings suggest that SUMO2/3 modification plays a key role in regulating RhoGDI1 stability and cell proliferation, while SUMO1 modification does not participate in these processes.
Purpose 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. Methods 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. Results 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. Conclusion This study reveals the differences between SUMO2/3 and SUMO1 modification in regulating RhoGDI1 stability and Ang II-mediated cell proliferation.
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