| First Author | Jeong EI | Year | 2016 |
| Journal | Cell Death Dis | Volume | 7 |
| Issue | 12 | Pages | e2573 |
| PubMed ID | 28032866 | Mgi Jnum | J:253302 |
| Mgi Id | MGI:6109776 | Doi | 10.1038/cddis.2016.428 |
| Citation | Jeong EI, et al. (2016) E2-25K SUMOylation inhibits proteasome for cell death during cerebral ischemia/reperfusion. Cell Death Dis 7(12):e2573 |
| abstractText | 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. |
