Characterization of the regulatory roles of the SUMO
DC Field | Value | Language |
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dc.contributor.author | Hwang, Kwang Woo | - |
dc.contributor.author | Won, Tae Joon | - |
dc.contributor.author | Kim, Hyunok | - |
dc.contributor.author | Chun, Ha-Jung | - |
dc.contributor.author | Chun, Taehoon | - |
dc.contributor.author | Park, Yongsoo | - |
dc.date.accessioned | 2022-01-06T03:40:21Z | - |
dc.date.available | 2022-01-06T03:40:21Z | - |
dc.date.issued | 2011-11 | - |
dc.identifier.issn | 1520-7552 | - |
dc.identifier.issn | 1520-7560 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/52940 | - |
dc.description.abstract | Background Type 1 diabetes is a multi-factorial autoimmune disease that results from the destruction of insulin-producing beta cells of the pancreas; both genetic and environmental factors are thought to contribute to its development. Recently, a novel gene encoding small ubiquitin-like modifier protein 4 (SUMO4) was cloned and a single nucleotide substitution (M55V) was found to be strongly associated with type 1 diabetes. SUMO4 was shown to interact with I kappa B alpha and inhibit NF kappa B transcriptional activity. The M55V substitution of SUMO4 may affect its ability to modify I kappa B alpha by sumoylation, and so lead to activation of NF kappa B and transcription of genes implicated in the development of type 1 diabetes. However, the effects of sumoylation on immune cells are poorly understood. Methods Human SUMO1, 2, 3, 4 and mouse SUMO2 (mSUMO2) were cloned and overexpressed in dendritic, T and B cells using retroviral transduction. We then investigated whether SUMO overexpression affected their functions in vitro. To study the function of mSUMO2 in vivo, we made transgenic mice overexpressing mSUMO2 in T cells and pancreatic beta cells and compared them with transgenic mice expressing a super-repressor of NF kappa B (a dominant negative form of NF kappa B, I kappa B alpha Delta N) in T cells. Diabetes was induced in the two groups of mice by i.p. injection of streptozotocin. Results Human SUMO1, 2, 3, 4 and mSUMO2 were all found to negatively regulate the transcriptional activity of T, B and dendritic cells. Although mSUMO2 overexpression in dendritic cells did not alter the expression of major histocompatibility complex class II proteins or B7, IL-1, IL-6 and IL-7, IL-12 expression decreased, switching Th1-directed immune responses into Th2 responses. Unlike T cells from the I kappa B alpha Delta N mice, mSUMO2 overexpression in T cells suppressed the production of both Th1 and Th2 cytokines. Whereas the mice overexpressing I kappa B alpha Delta N were completely protected against diabetes, those expressing mSUMO2 had the same susceptibility to diabetes as wild type. Conclusion These results indicate that at least in T cells, whereas NF kappa B has pro-apoptotic activity, mSUMO2 plays a more complex role in the development of autoimmune diabetes. The relative influence of NF kappa B and sumoylation on the development of autoimmune diabetes in vivo may vary depending on the developmental stage and cell type. Copyright (C) 2011 John Wiley & Sons, Ltd. | - |
dc.format.extent | 8 | - |
dc.language | 영어 | - |
dc.language.iso | ENG | - |
dc.publisher | WILEY | - |
dc.title | Characterization of the regulatory roles of the SUMO | - |
dc.type | Article | - |
dc.identifier.doi | 10.1002/dmrr.1261 | - |
dc.identifier.bibliographicCitation | DIABETES-METABOLISM RESEARCH AND REVIEWS, v.27, no.8, pp 854 - 861 | - |
dc.description.isOpenAccess | N | - |
dc.identifier.wosid | 000300108000024 | - |
dc.identifier.scopusid | 2-s2.0-80855124146 | - |
dc.citation.endPage | 861 | - |
dc.citation.number | 8 | - |
dc.citation.startPage | 854 | - |
dc.citation.title | DIABETES-METABOLISM RESEARCH AND REVIEWS | - |
dc.citation.volume | 27 | - |
dc.type.docType | Article; Proceedings Paper | - |
dc.subject.keywordAuthor | type 1 diabetes | - |
dc.subject.keywordAuthor | sumoylation | - |
dc.subject.keywordAuthor | immune cells | - |
dc.subject.keywordAuthor | SUMO2 | - |
dc.subject.keywordAuthor | NF kappa B | - |
dc.subject.keywordAuthor | IDDM5 | - |
dc.subject.keywordPlus | NF-KAPPA-B | - |
dc.subject.keywordPlus | MODIFIER | - |
dc.subject.keywordPlus | VARIANT | - |
dc.relation.journalResearchArea | Endocrinology & Metabolism | - |
dc.relation.journalWebOfScienceCategory | Endocrinology & Metabolism | - |
dc.description.journalRegisteredClass | sci | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
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