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-κB 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.
Bibliographical noteFunding Information:
This study was supported by grants from the Korea Health 21 R&D Project (A080551 to K.C.C.) funded by Ministry of Health & Welfare and from the Korea Science and Engineering Foundation (KOSEF; R11-2007-040-01005-0 and R01-2007-000-20089-0 to K.C.C.) funded by Ministry of Science and Technology, Republic of Korea. This work was also partly supported by KOSEF grant through National Research Laboratory Program (R04-2007-000-20014-0 to K.C.C.).
All Science Journal Classification (ASJC) codes
- Molecular Biology