NF-kappa B-inducing kinase phosphorylates and blocks the degradation of down syndrome candidate region 1
DC Field | Value | Language |
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dc.contributor.author | Lee, Jung | - |
dc.contributor.author | Seo, Su Ryeon | - |
dc.contributor.author | Wonum, Ji | - |
dc.contributor.author | Park, Joongkyu | - |
dc.contributor.author | Oh, Yohan | - |
dc.contributor.author | Chung, Kwang Chul | - |
dc.date.accessioned | 2022-12-21T04:43:04Z | - |
dc.date.available | 2022-12-21T04:43:04Z | - |
dc.date.created | 2021-10-15 | - |
dc.date.issued | 2008-02 | - |
dc.identifier.issn | 0021-9258 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/179044 | - |
dc.description.abstract | Down syndrome, the most frequent genetic disorder, is characterized by an extra copy of all or part of chromosome 21. Down syndrome candidate region 1 (DSCR1) gene, which is located on chromosome 21, is highly expressed in the brain of Down syndrome patients. Although its cellular function remains unknown, DSCR1 expression is linked to inflammation, angiogenesis, and cardiac development. To explore the functional role of DSCR1 and the regulation of its expression, we searched for novel DSCR1-interacting proteins using a yeast two-hybrid assay. Using a human fetal brain library, we found that DSCR1 interacts with NF-kappa B-inducing kinase (NIK). Furthermore, we demonstrate that NIK specifically interacts with and phosphorylates the C-terminal region of DSCR1 in immortalized hippocampal cells as well as in primary cortical neurons. This NIK-mediated phosphorylation of DSCR1 increases its protein stability and blocks its proteasomal degradation, the effects of which lead to an increase in soluble and insoluble DSCR1 levels. We show that an increase in insoluble DSCR1 levels results in the formation of cytosolic aggregates. Interestingly, we found that whereas the formation of these inclusions does not significantly alter the viability of neuronal cells, the overexpression of DSCR1 without the formation of aggregates is cytotoxic. | - |
dc.language | 영어 | - |
dc.language.iso | en | - |
dc.publisher | American Society for Biochemistry and Molecular Biology Inc. | - |
dc.title | NF-kappa B-inducing kinase phosphorylates and blocks the degradation of down syndrome candidate region 1 | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Oh, Yohan | - |
dc.identifier.doi | 10.1074/jbc.M706707200 | - |
dc.identifier.scopusid | 2-s2.0-41249098372 | - |
dc.identifier.wosid | 000253083000044 | - |
dc.identifier.bibliographicCitation | Journal of Biological Chemistry, v.283, pp.3392 - 3400 | - |
dc.relation.isPartOf | Journal of Biological Chemistry | - |
dc.citation.title | Journal of Biological Chemistry | - |
dc.citation.volume | 283 | - |
dc.citation.startPage | 3392 | - |
dc.citation.endPage | 3400 | - |
dc.type.rims | ART | - |
dc.description.journalClass | 1 | - |
dc.description.isOpenAccess | Y | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Biochemistry & Molecular Biology | - |
dc.relation.journalWebOfScienceCategory | Biochemistry & Molecular Biology | - |
dc.subject.keywordPlus | Agglomeration | - |
dc.subject.keywordPlus | Chromosomes | - |
dc.subject.keywordPlus | Degradation | - |
dc.identifier.url | https://www.sciencedirect.com/science/article/pii/S0021925820698039?via%3Dihub | - |
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