Research ReportHuman Polycomb protein 2 promotes α-synuclein aggregate formation through covalent SUMOylation

Parkinson's disease (PD) manifests from the impairment of motor systems due to the specific loss of dopaminergic neurons and the appearance of intracellular filamentous inclusions called Lewy bodies (LBs). α-Synuclein, a major component of LBs, is known to contribute to the pathogenesis of PD. Although α-synuclein is known to be a target of diverse posttranslational modifications, the contribution of α-synuclein SUMOylation and its functional consequences have not yet been fully characterized. Here, we demonstrate that human Polycomb protein 2 (hPc2) binds to α-synuclein and may function as a SUMO E3 ligase to promote the SUMOylation of α-synuclein. In addition, hPc2 promotes the SUMOylation of α-synuclein in the presence of MG-132-induced proteasome inhibition, which consequently promotes α-synuclein aggregate formation. Furthermore, the increased formation of intracellular α-synuclein aggregates, which predominantly contain SUMOylated α-synuclein, significantly reduces the death of fibroblast cells in response to staurosporine. In summary, the results from this study demonstrate that the hPc2-induced SUMOylation of α-synuclein could function as a cytoprotector by increasing α-synuclein aggregate formation within fibroblast cells.

Research Highlights► SUMO E3 ligase hPc2 binds to α-synuclein and promotes its covalent SUMOylation. ► hPc2 stimulates α-synuclein aggregate formation. ► hPc2-induced SUMOylation of α-synuclein could function as a cytoprotector.