Reseach on RNA helicase, MOV10, which negatively regulates NF-kappaB activation

异位表达MOV10可明显抑制Jurkat T细胞中核因子-kappaB的活化。但在Jurkat T细胞中敲除MOV10并不影响核因子-kappaB的激活。或者，我们进行了一项基于细胞的筛选，以寻找TCR介导的NF-kappaB激活的负调控因子。我们发现酪蛋白激酶-2相互作用蛋白-1(CKIP-1)抑制PKCtheta-CBM-NF-kappaB信号转导。我们发现CKIP-1与CARMA1相互作用，并与PKCtheta竞争结合。CKIP-1抑制未经刺激的细胞中的NF-kappaB活性，并抑制由PMA或结构性活性PKCtheta刺激而不是由TNFalfa刺激所诱导的NF-kappaB的激活。这些数据表明，CKIP-1有助于维持NF-kappaB活性的静息状态，或防止T细胞因信号不充分而被激活。总之，我们证明了CKIP-1与CARMA1相互作用，并对PKCtheta-CBM-NF-kappaB信号具有抑制作用。

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.