Human 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.
Department of Biology, College of Life Science and Biotechnology, Yonsei University, Seoul, Republic of Korea.
Yohan
Y
Oh
Yong Man
YM
Kim
M Maral
MM
Mouradian
Kwang Chul
KC
Chung
D000818:Animals; D015153:Blotting, Western; D019556:COS Cells; D002458:Cell Fractionation; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008025:Ligases; D063146:Polycomb-Group Proteins; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D011485:Protein Binding; D012097:Repressor Proteins / Q000378:metabolism*; D025842:SUMO-1 Protein / Q000378:metabolism*; D058207:Sumoylation / Q000502:physiology*; D014162:Transfection; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D051844:alpha-Synuclein / Q000378:metabolism*
D063146:Polycomb-Group Proteins; D012097:Repressor Proteins; D025842:SUMO-1 Protein; C495501:SUMO1 protein, human; D051844:alpha-Synuclein; D044767:Ubiquitin-Protein Ligases; D046988:Proteasome Endopeptidase Complex; D008025:Ligases; C570427:CBX4 protein, human