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

Yohan Oh; Yong Man Kim; M. Maral Mouradian; Kwang Chul Chung

doi:10.1016/j.brainres.2011.01.039

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

Yohan Oh, Yong Man Kim, M. Maral Mouradian, Kwang Chul Chung

Research output: Contribution to journal › Article › peer-review

38 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	78-89
Number of pages	12
Journal	Brain Research
Volume	1381
DOIs	https://doi.org/10.1016/j.brainres.2011.01.039
Publication status	Published - 2011 Mar 24

Bibliographical note

Funding 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

Neuroscience(all)
Molecular Biology
Clinical Neurology
Developmental Biology

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title = "Human Polycomb protein 2 promotes α-synuclein aggregate formation through covalent SUMOylation",

abstract = "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.",

author = "Yohan Oh and Kim, {Yong Man} and Mouradian, {M. Maral} and Chung, {Kwang Chul}",

note = "Funding 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.). ",

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AU - Chung, Kwang Chul

N1 - Funding 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.).

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AB - 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.

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