Document Detail


Down syndrome candidate region-1 protein interacts with Tollip and positively modulates interleukin-1 receptor-mediated signaling.
MedLine Citation:
PMID:  19716405     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: The Down syndrome candidate region-1 gene (DSCR1, also known as RCAN1) is situated close to the Down Syndrome Critical Region (DSCR), which contains genes responsible for many features of Down syndrome. DSCR1 modulates calcineurin phosphatase activity, though its functional role is incompletely understood.
METHODS: Here we investigated the role of DSCR1-1S isoform in IL-1 receptor (IL-1R)-mediated signaling by analyzing interaction between DSCR1-1S and the IL-1R pathway components Tollip, IRAK-1, and TRAF6.
RESULTS: Co-immunoprecipitation analyses of HEK293 cells revealed that DSCR1-1S interacted with Tollip, an IRAK-1 inhibitor, leading to the dissociation of IRAK-1 from Tollip. Similarly, both DSCR1-1S and Tollip interacted with TRAF6, with DSCR1 reducing interaction between Tollip and TRAF6. DSCR1-1S also stimulated IL-1R-mediated signaling pathways, TAK1 activation, NF-kappaB transactivation, and IL-8 production, all downstream consequences of IL-1R activation.
GENERAL SIGNIFICANCE: Together, these results suggest that DSCR1-1S isoform positively modulates IL-1R-mediated signaling pathways by regulating Tollip/IRAK-1/TRAF6 complex formation.
Authors:
Jae Youn Lee; Hyun Jung Lee; Eun Jung Lee; Sung Hee Jang; Hyeyoung Kim; Joo-Heon Yoon; Kwang Chul Chung
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-08-27
Journal Detail:
Title:  Biochimica et biophysica acta     Volume:  1790     ISSN:  0006-3002     ISO Abbreviation:  Biochim. Biophys. Acta     Publication Date:  2009 Dec 
Date Detail:
Created Date:  2009-11-16     Completed Date:  2010-03-04     Revised Date:  2012-06-27    
Medline Journal Info:
Nlm Unique ID:  0217513     Medline TA:  Biochim Biophys Acta     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  1673-80     Citation Subset:  IM    
Affiliation:
Department of Biology, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, Korea.
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MeSH Terms
Descriptor/Qualifier:
Cells, Cultured
Humans
Interleukin-1 Receptor-Associated Kinases / metabolism
Interleukin-8 / metabolism
Intracellular Signaling Peptides and Proteins / chemistry,  metabolism*,  physiology*
Models, Biological
Muscle Proteins / chemistry,  metabolism*,  physiology*
NF-kappa B / metabolism
Protein Binding
Protein Interaction Domains and Motifs / physiology
Protein Isoforms / metabolism,  physiology
Receptors, Interleukin-1 / metabolism,  physiology*
Signal Transduction / physiology
TNF Receptor-Associated Factor 6 / metabolism
Up-Regulation
Chemical
Reg. No./Substance:
0/Interleukin-8; 0/Intracellular Signaling Peptides and Proteins; 0/Muscle Proteins; 0/NF-kappa B; 0/Protein Isoforms; 0/RCAN1 protein, human; 0/Receptors, Interleukin-1; 0/TNF Receptor-Associated Factor 6; 0/TOLLIP protein, human; EC 2.7.11.1/IRAK1 protein, human; EC 2.7.11.1/Interleukin-1 Receptor-Associated Kinases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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