title: E2-25K SUMOylation inhibits proteasome for cell death during cerebral ischemia/reperfusion.
abstract: Cerebral ischemia/reperfusion (I/R) causes brain damage accompanied by ubiquitin accumulation and impairment of proteasome activity. In this study, we report that E2-25K, an E2-conjugating enzyme, is SUMOylated during oxidative stress and regulates cerebral I/R-induced damage. Knockdown of E2-25K expression protects against oxygen/glucose deprivation and reoxygenation (OGD/R)-induced neuronal cell death, whereas ectopic expression of E2-25K stimulates it. Compared with the control mice, cerebral infarction lesions and behavioral/neurological disorders are ameliorated in E2-25K knockout mice during middle cerebral artery occlusion and reperfusion. In particular, E2-25K is SUMOylated at Lys14 under oxidative stress, OGD/R and I/R to prompt cell death. Further, E2-25K downregulates the proteasome subunit S5a to impair proteasome complex and thus restrain proteasome activity under oxidative stress. This proteasome inhibitory activity of E2-25K is dependent on its SUMOylation. These results suggest that E2-25K has a crucial role in oxidative stress and cerebral I/R-induced damage through inhibiting proteasome via its SUMOylation.
authors.affiliation: Global Research Laboratory, Department of Biological Science, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 151-747, Korea.
authors.forename: Eun Il
authors.initials: EI
authors.lastname: Jeong
authors.affiliation: Global Research Laboratory, Department of Biological Science, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 151-747, Korea.
authors.forename: Hae Won
authors.initials: HW
authors.lastname: Chung
authors.affiliation: Global Research Laboratory, Department of Biological Science, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 151-747, Korea.
authors.forename: Won Jea
authors.initials: WJ
authors.lastname: Lee
authors.affiliation: Global Research Laboratory, Department of Biological Science, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 151-747, Korea.
authors.forename: Seo-Hyun
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Global Research Laboratory, Department of Biological Science, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 151-747, Korea.
authors.forename: Hyunjoo
authors.initials: H
authors.lastname: Kim
authors.affiliation: Global Research Laboratory, Department of Biological Science, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 151-747, Korea.
authors.forename: Seon-Guk
authors.initials: SG
authors.lastname: Choi
authors.affiliation: Global Research Laboratory, Department of Biological Science, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 151-747, Korea.
authors.forename: Yong-Keun
authors.initials: YK
authors.lastname: Jung
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000150:complications / Q000201:enzymology* / Q000473:pathology*; D002352:Carrier Proteins / Q000378:metabolism; D016923:Cell Death; D015536:Down-Regulation; D005947:Glucose / Q000172:deficiency; D020244:Infarction, Middle Cerebral Artery / Q000150:complications / Q000201:enzymology / Q000473:pathology; D008239:Lysine / Q000378:metabolism; D008297:Male; D018345:Mice, Knockout; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress; D010100:Oxygen; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D016601:RNA-Binding Proteins; D015427:Reperfusion Injury / Q000150:complications / Q000201:enzymology* / Q000473:pathology*; D058207:Sumoylation; D044763:Ubiquitin-Conjugating Enzymes / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; C490781:Psmd4 protein, mouse; D016601:RNA-Binding Proteins; C531382:Ube2k protein, mouse; D044763:Ubiquitin-Conjugating Enzymes; D046988:Proteasome Endopeptidase Complex; D005947:Glucose; D008239:Lysine; D010100:Oxygen