Matsumura Takayuki, Semba Kentaro, Azuma Sakura, Ikawa Shuntaro, Gohda Jin, Akiyama Taishin, Inoue Jun-ichiro
Division of Cellular and Molecular Biology, Department of Cancer Biology, Institute of Medical Science, University of Tokyo, Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
Biochem Biophys Res Commun. 2004 Apr 23;317(1):230-4. doi: 10.1016/j.bbrc.2004.03.030.
Tumor necrosis factor receptor-associated factor 6 (TRAF6) transduces signals that lead to activation of NFkappaB and AP-1, which is essential for cell differentiation and establishment of the immune and inflammatory systems. TRAF-interacting protein with a forkhead-associated domain (TIFA) was identified as a TRAF6-binding protein that could link IRAK-1 to TRAF6 and then activate TRAF6 upon stimulation. We report identification of a TIFA-related protein, TIFAB, that inhibits TIFA-mediated activation of NFkappaB. TIFAB does not associate with members of the TRAF family but does bind TIFA. We analyzed the effect of TIFAB expression on the TRAF6/TIFA interaction by immunoprecipitation of TRAF6 and found that TIFA coprecipitated with TRAF6 was not changed. However, when we analyzed this interaction by immunoprecipitation of TIFA, we found that TIFAB significantly increased the amount of TRAF6 coprecipitated with TIFA. These findings suggest that TIFAB inhibits the TIFA-mediated TRAF6 activation possibly by inducing a conformational change in TIFA.
肿瘤坏死因子受体相关因子6（TRAF6）转导导致核因子κB（NFκB）和活化蛋白-1（AP-1）激活的信号，这对于细胞分化以及免疫和炎症系统的建立至关重要。具有叉头相关结构域的TRAF相互作用蛋白（TIFA）被鉴定为一种TRAF6结合蛋白，它可将白细胞介素-1受体相关激酶-1（IRAK-1）与TRAF6连接起来，进而在受到刺激时激活TRAF6。我们报告了一种与TIFA相关的蛋白TIFAB的鉴定，该蛋白可抑制TIFA介导的NFκB激活。TIFAB不与TRAF家族成员结合，但能与TIFA结合。我们通过对TRAF6进行免疫沉淀来分析TIFAB表达对TRAF6/TIFA相互作用的影响，发现与TRAF6共沉淀的TIFA没有变化。然而，当我们通过对TIFA进行免疫沉淀来分析这种相互作用时，发现TIFAB显著增加了与TIFA共沉淀的TRAF6的量。这些发现表明，TIFAB可能通过诱导TIFA的构象变化来抑制TIFA介导的TRAF6激活。
