Aizawa S, Nakano H, Ishida T, Horie R, Nagai M, Ito K, Yagita H, Okumura K, Inoue J, Watanabe T
Department of Pathology, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108, Japan.
J Biol Chem. 1997 Jan 24;272(4):2042-5. doi: 10.1074/jbc.272.4.2042.
Signals emanated from CD30 can activate the nuclear factor kappaB (NFkappaB). The two conserved subdomains, D1 and D2, in the C-terminal cytoplasmic region of CD30 were tested for interaction with two tumor necrosis factor receptor-associated factor (TRAF) proteins with NFkappaB activating capacity, TRAF2 and TRAF5. TRAF5 is the newest member of the TRAF family that binds to lymphotoxin beta receptor and CD40. TRAF5, as well as TRAF2, interacted with the D2 subdomain of CD30 in vitro and in vivo. Deletion analysis by the yeast two-hybrid system revealed that the C-terminal 22 and 30 amino acid residues are dispensable for interaction of TRAF5 and TRAF2 with CD30, respectively. Substitution of alanine for threonine at 463 abolished the interaction with TRAF2. Overexpression of the TRAF domain of TRAF2 or TRAF5 showed a dominant negative effect on CD30-mediated NFkappaB activation. Simultaneous expression of these TRAF domains further suppressed the NFkappaB activation, suggesting an interplay of these TRAF proteins. Expression of TRAF2 and TRAF5 mRNA was demonstrated in T- and B-cell lines that express CD30. Taken together, our results indicate that TRAF2 and TRAF5 directly interact with CD30 and are involved in NFkappaB activation by CD30 signaling.
源自CD30的信号可激活核因子κB（NFκB）。对CD30 C末端胞质区域中的两个保守亚结构域D1和D2进行了检测，以确定它们与两种具有NFκB激活能力的肿瘤坏死因子受体相关因子（TRAF）蛋白TRAF2和TRAF5的相互作用。TRAF5是TRAF家族的最新成员，可与淋巴毒素β受体和CD40结合。TRAF5以及TRAF2在体外和体内均与CD30的D2亚结构域相互作用。酵母双杂交系统的缺失分析表明，TRAF5和TRAF2与CD30相互作用时，C末端的22个和30个氨基酸残基分别是可有可无的。463位的苏氨酸被丙氨酸取代消除了与TRAF2的相互作用。TRAF2或TRAF5的TRAF结构域的过表达对CD30介导的NFκB激活具有显性负效应。这些TRAF结构域的同时表达进一步抑制了NFκB激活，表明这些TRAF蛋白之间存在相互作用。在表达CD30的T细胞和B细胞系中证实了TRAF2和TRAF5 mRNA的表达。综上所述，我们的结果表明TRAF2和TRAF5直接与CD30相互作用，并参与CD30信号传导介导的NFκB激活。
