Linked Life Data

18056702

Source:http://linkedlifedata.com/resource/pubmed/id/18056702

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2008-2-4
pubmed:abstractText
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-kappaB-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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
8
pubmed:volume
283
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3392-400
pubmed:dateRevised
2011-11-2
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
NF-kappaB-inducing kinase phosphorylates and blocks the degradation of Down syndrome candidate region 1.
pubmed:affiliation
Department of Biology, College of Science, Yonsei University, Seoul 120-749, Korea.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't