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.
Bibliographical noteFunding Information:
This study was supported from a grant from the Brain Research Center of the 21st Century Frontier Research Program Technology ( 2009K-001251 to K.C.C.), which is funded by the Ministry of Education, Science and Technology (MEST), Republic of Korea . This work was also supported by grants from National Research Foundation of Korea (NRF) ( 2010-0018916 to K.C.C.) and from Basic Science Research Program through NRF ( 2010-0001668 to K.C.C.) funded by MEST. This work was also partially supported by a grant from the Korea Healthcare technology R&D Project, Ministry for Health, Welfare & Family Affairs, Republic of Korea ( A092004 to K.C.C.).
All Science Journal Classification (ASJC) codes
- Molecular Biology
- Clinical Neurology
- Developmental Biology