Four small ubiquitin-like modifier (SUMO) isoforms termed SUMO-1, -2, -3 and -4 have been identified in human. Most SUMO-1/2 proteins are localized in nucleus, whereas SUMO-1 protein exhibits 44% homolog with SUMO-2 protein. Over 50 proteins have been identified as the target proteins for SUMO-1 modification and these include transcription factors, their cofactors, regulators, nuclear body proteins, nuclear pore complex proteins, DNA repair proteins, and viral proteins. However, only a handful of SUMO-2 targets are known and SUMO-2 modification may response to environmental stress. SUMO-1 may interact with Fas/APO-1 and TNF receptor 1 on yeast two hybrid interactions; however, it is not clear whether SUMO would enhance apoptosis or response to biological stress. Helicobacter pylori (H. pylori) defined as a gastric carcinogen is definite a biological stress to the cells. It causes gastric epithelial cell damage by apoptosis. In this study whether the SUMO-1/2 pathway constitutes an element of the cellular response to the H. pylori infection was examined. Overexpression of SUMO-1/2 for 12 hours had no effects on the apoptotic activities of cells; however it enhanced apoptosis during H. pylori infection. Overexpression of SUMO-1/2 for 48 hours increased the apoptosis of cells; however only SUMO-2 enhanced apoptosis significantly during H. pylori infection. The enhancements are more powerful for SUMO-2 than that of SUMO-1. Inactive SUMO, a cytoplasm dispersed sumoylation-incompetent mutant, eliminates such activities, suggesting that sumoylation or SUMO interactions are involved in the apoptotic enhancement. The percentages of cells with cytoplasmic SUMO-2 were increased 22% by H. pylori infection for 2 hours and SUMO-1 were increased 11%. The translocalization of SUMO-1 was blocked by leptomycin B; however, it did not work on SUMO-2. Leptomycin B could also inhibit SUMO-1 enhanced apoptosis during H. pylori infection, whereas it had no effects on SUMO-2. It is concluded that SUMO-1/2 pathway constitutes an element of the cellular response to H. pylori infection by enhancing apoptosis through shuttling from nucleus to cytoplasm. SUMO-1 is via a CRM1-dependent pathway while SUMO-2 is via a CRM1-independent pathway.
| Identifer | oai:union.ndltd.org:NSYSU/oai:NSYSU:etd-0809106-124752 |
| Date | 09 August 2006 |
| Creators | Yang, Chia-lin |
| Contributors | Deng-Chung Wu, Wen-Chun Hung, Angela Chen |
| Publisher | NSYSU |
| Source Sets | NSYSU Electronic Thesis and Dissertation Archive |
| Language | Cholon |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-0809106-124752 |
| Rights | not_available, Copyright information available at source archive |
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