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

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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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This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.brainres.2011.01.039

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

Abstract

Bibliographical note

All Science Journal Classification (ASJC) codes

UN SDGs

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