A new domain in the Toll/IL-1R domain-containing adaptor inducing interferon-β factor protein amino terminus is important for tumor necrosis factor-α receptor-associated factor 3 association, protein stabilization and interferon signaling.
A new domain in the Toll/IL-1R domain-containing adaptor inducing interferon-β factor protein amino terminus is important for tumor necrosis factor-α receptor-associated factor 3 association, protein stabilization and interferon signaling.
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DOI：
10.1159/000356408
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发表时间：
2014
影响因子：
5.3
通讯作者：
Waldmann TA
中科院分区：
文献类型：
--
作者：
Nguyen VP;Chen J;Petrus MN;Goldman CK;Kruhlak MJ;Bamford RN;Waldmann TA
含有 Toll/IL-1R 结构域的接头诱导 IFN-β 因子 (TRIF) 是 Toll 样受体 (TLR) 3 和 4 信号转导的关键接头。使用编码 TRIF 蛋白的新型 cDNA 分离物，该蛋白的氨基末端有 21 个残基缺失 (Δ160-181)，我们研究了该缺失对 TRIF 功能的影响。转染研究一致显示，与野生型 (wt) TRIF 相比，(Δ160-181) TRIF 的表达水平较高，这种效应与细胞凋亡、细胞系或质粒扩增无关。 wt 和 (Δ160-181) TRIF 蛋白的共定位导致它们各自表达的急剧减少，表明 wt/(Δ160-181) TRIF 杂复合物是降解的目标。我们证明 wt TRIF 与 TRAF3 的结合优于 (Δ160-181) TRIF，最终导致其更强的泛素化和蛋白水解作用。这部分解释了两种 TRIF 蛋白的差异表达水平。尽管转染细胞中的表达水平较高，但 (Δ160-181) TRIF 不能有效地反式激活干扰素途径，而 NF-κB 途径激活仍与 wt TRIF 相似。在共表达研究中，(Δ160-181) TRIF 对干扰素通路激活略有贡献，但仍然增强了 wt TRIF 的 NF-κB 信号传导。因此，这 21 个氨基酸序列对于 TRAF3 关联、TRIF 稳定性调节和干扰素途径激活至关重要。
Toll/IL-1R domain-containing adaptor inducing IFN-β factor (TRIF) is a key adapter for Toll-like receptor (TLR) 3 and 4 signaling. Using a novel cDNA isolate encoding a TRIF protein with a 21-residue deletion (Δ160-181) from its amino-terminal half, we investigated the impact of this deletion on TRIF functions. Transfection studies consistently showed higher expression levels of the (Δ160-181) TRIF compared to wild-type (wt) TRIF, an effect unrelated to apoptosis, cell lines, or plasmid amplification. Colocalization of wt and (Δ160-181) TRIF proteins led to a dramatic reduction of their respective expressions, suggesting that wt/(Δ160-181) TRIF heterocomplexes are targeted for degradation. We demonstrated that wt TRIF associates with TRAF3 better than (Δ160-181) TRIF, culminating in its greater ubiquitination and proteolysis. This explains, in part, the differential expression levels of the two TRIF proteins. Despite higher expression levels in transfected cells, (Δ160-181) TRIF inefficiently transactivated the interferon pathway, whereas the NF-κB pathway activation remained similar to that by wt TRIF. In co-expression studies, (Δ160-181) TRIF marginally contributed to the interferon pathway activation, but still enhanced NF-κB signaling with wt TRIF. Therefore, this 21 amino acid sequence is crucial for TRAF3 association, modulation of TRIF stability and activation of the interferon pathway.
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影响因子：
32.4
作者：
Kawai, T;Adachi, O;Akira, S
通讯作者：
Akira, S
DOI：
10.1073/pnas.0308496101
发表时间：
2004-03-09
影响因子：
11.1
作者：
Jiang, ZF;Mak, TW;Li, XX
通讯作者：
Li, XX
影响因子：
4.4
作者：
Kaiser, WJ;Offermann, MK
通讯作者：
Offermann, MK
影响因子：
4.4
作者：
Funami, K;Matsumoto, M;Seya, T
通讯作者：
Seya, T
影响因子：
32.4
作者：
Pérez de Diego R;Sancho-Shimizu V;Lorenzo L;Puel A;Plancoulaine S;Picard C;Herman M;Cardon A;Durandy A;Bustamante J;Vallabhapurapu S;Bravo J;Warnatz K;Chaix Y;Cascarrigny F;Lebon P;Rozenberg F;Karin M;Tardieu M;Al-Muhsen S;Jouanguy E;Zhang SY;Abel L;Casanova JL
通讯作者：
Casanova JL