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The SUMO Conjugase Ubc9 Protects Dopaminergic Cells from Cytotoxicity and Enhances the Stability of α-Synuclein in Parkinson's Disease Models

eNeuro. 2020; 
Dinesh Kumar Verma, Anurupa Ghosh, Lindsey Ruggiero, Etienne Cartier, Eric Janezic, Dionne Williams, Eui-Gil Jung, Michael Moore, Jong Bok Seo, Yong-Hwan Kim
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Molecular Biology Reagents … Page 13. 12 by 4-20% SDS-PAGE gels (GenScript). Alpha-synuclein was detected by immunoblotting as described in 279 … All IP'ed samples 291 were separated by 4-20% SDS-PAGE gels (GenScript, Piscataway, NJ) along with 5% total lysate as 292 input … Get A Quote

摘要

Small ubiquitin-like modifier (SUMO) is a widespread regulatory mechanism of post-translational modification (PTM) that induces rapid and reversible changes in protein function and stability. Using SUMO conjugase Ubc9-overexpressing or knock-down cells in Parkinson's disease (PD) models, we demonstrate that SUMOylation protects dopaminergic cells against MPP+ or preformed fibrils (PFFs) of α-synuclein (α-syn)-induced toxicities in cell viability and cytotoxicity assays. In the mechanism of protection, Ubc9 overexpression significantly suppressed the MPP+ or PFF-induced reactive oxygen species (ROS) generation, while Ubc9-RNAi enhanced the toxicity-induced ROS production. Further, PFF-mediated protein aggregat... More

关键词

SUMOylation, Ubc9, degradation, lysosome, proteostasis, α-synuclein