Down syndrome candidate region-1 protein interacts with Tollip and positively modulates interleukin-1 receptor-mediated signaling

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 und...

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Vydáno v:	Biochimica et biophysica acta Ročník 1790; číslo 12; s. 1673 - 1680
Hlavní autoři:	Lee, Jae Youn, Lee, Hyun Jung, Lee, Eun Jung, Jang, Sung Hee, Kim, Hyeyoung, Yoon, Joo-Heon, Chung, Kwang Chul
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	Netherlands Elsevier B.V 01.12.2009
Témata:	Cells, Cultured Cytokine Down syndrome Down Syndrome Critical Region Humans IL-1 Inflammation Interleukin-1 Receptor-Associated Kinases - metabolism Interleukin-8 - metabolism Intracellular Signaling Peptides and Proteins - chemistry Intracellular Signaling Peptides and Proteins - metabolism Intracellular Signaling Peptides and Proteins - physiology Models, Biological Muscle Proteins - chemistry Muscle Proteins - metabolism Muscle Proteins - physiology NF-kappa B - metabolism Protein Binding Protein Interaction Domains and Motifs - physiology Protein Isoforms - metabolism Protein Isoforms - physiology Receptors, Interleukin-1 - metabolism Receptors, Interleukin-1 - physiology Signal Transduction - physiology TNF Receptor-Associated Factor 6 - metabolism Tollip Up-Regulation Inflammation Down syndrome Down Syndrome Critical Region IL-1 Cytokine Tollip
ISSN:	0304-4165, 0006-3002, 1872-8006
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Shrnutí:	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. 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. 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-κB transactivation, and IL-8 production, all downstream consequences of IL-1R activation. Together, these results suggest that DSCR1-1S isoform positively modulates IL-1R-mediated signaling pathways by regulating Tollip/IRAK-1/TRAF6 complex formation.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0304-4165 0006-3002 1872-8006
DOI:	10.1016/j.bbagen.2009.08.005