| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Research Abstract |
Ectopic MOV10 expression clearly suppressed NF-kappaB activation in Jurkat T cells. But knock down of MOV10 in Jurkat T cells didn't affect NF-kappaB activation. Alternatively we performed a cell-based screening for negative regulators of TCR-mediated NF-kappaB activation. We found that casein kinase-2 interacting protein-1 (CKIP-1) suppresses PKCtheta-CBM-NF-kappaB signaling. We found that CKIP-1 interacts with CARMA1 and competes with PKCtheta for association. CKIP-1 represses NF-kappaB activity in unstimulated cells, and inhibits NF-kappaB activation induced by stimulation with PMA or constitutively active PKCtheta, but not by stimulation with TNFalfa. These data suggest that CKIP-1 contributes maintenance of a resting state on NF-kappaB activity or prevents T cells from being activated by inadequate signaling. In conclusion, we demonstrate that CKIP-1 interacts with CARMA1 and has an inhibitory effect on PKCtheta-CBM-NF-kappaB signaling.
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