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 |
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| Médium: | Journal Article |
| Jazyk: | angličtina |
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Netherlands
Elsevier B.V
01.12.2009
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| ISSN: | 0304-4165, 0006-3002, 1872-8006 |
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| Abstract | 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. |
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| AbstractList | 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-kappaB 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. 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.BACKGROUNDThe 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.METHODSHere 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-kappaB transactivation, and IL-8 production, all downstream consequences of IL-1R activation.RESULTSCo-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.Together, these results suggest that DSCR1-1S isoform positively modulates IL-1R-mediated signaling pathways by regulating Tollip/IRAK-1/TRAF6 complex formation.GENERAL SIGNIFICANCETogether, these results suggest that DSCR1-1S isoform positively modulates IL-1R-mediated signaling pathways by regulating Tollip/IRAK-1/TRAF6 complex formation. 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. |
| Author | Chung, Kwang Chul Lee, Hyun Jung Jang, Sung Hee Lee, Jae Youn Yoon, Joo-Heon Kim, Hyeyoung Lee, Eun Jung |
| Author_xml | – sequence: 1 givenname: Jae Youn surname: Lee fullname: Lee, Jae Youn organization: Department of Biology, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, Korea – sequence: 2 givenname: Hyun Jung surname: Lee fullname: Lee, Hyun Jung organization: Department of Biology, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, Korea – sequence: 3 givenname: Eun Jung surname: Lee fullname: Lee, Eun Jung organization: Department of Biology, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, Korea – sequence: 4 givenname: Sung Hee surname: Jang fullname: Jang, Sung Hee organization: Department of Food and Nutrition, Seoul 120-749, Korea – sequence: 5 givenname: Hyeyoung surname: Kim fullname: Kim, Hyeyoung organization: Department of Food and Nutrition, Seoul 120-749, Korea – sequence: 6 givenname: Joo-Heon surname: Yoon fullname: Yoon, Joo-Heon organization: Department of Otorhinolaryngology, Yonsei University College of Medicine, Seoul 120-752, Korea – sequence: 7 givenname: Kwang Chul surname: Chung fullname: Chung, Kwang Chul email: kchung@yonsei.ac.kr organization: Department of Biology, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, Korea |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/19716405$$D View this record in MEDLINE/PubMed |
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| Keywords | Inflammation Down syndrome Down Syndrome Critical Region IL-1 Cytokine Tollip |
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Down syndrome candidate region-1 gene (
DSCR1, also known as
RCAN1) is situated close to the Down Syndrome Critical Region (DSCR), which contains genes... 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... |
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| SubjectTerms | 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 |
| Title | Down syndrome candidate region-1 protein interacts with Tollip and positively modulates interleukin-1 receptor-mediated signaling |
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