Role of the TAB2-related protein TAB3 in IL-1 and TNF signaling
Role of the TAB2-related protein TAB3 in IL-1 and TNF signaling
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DOI：
10.1093/emboj/cdg605
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发表时间：
2003-12-01
期刊：
影响因子：
11.4
通讯作者：
Matsumoto, K
中科院分区：
文献类型：
--
作者：
Ishitani, T;Takaesu, G;Matsumoto, K
细胞因子IL-1和TNF诱导一系列基因的表达，这些基因通过激活NF-kappaB信号转导通路来调节炎症。TAK1是一种MAPKKK，对于IL-1和tnf诱导的NF-kappaB通路的激活都是至关重要的。TAB2是TAK1结合蛋白，通过将TAK1与TRAF6物理连接，参与il -1诱导的NF-kappaB激活。然而，il -1诱导的NF-kappaB激活在tab2缺陷的胚胎成纤维细胞中不受损害。在这里，我们报告了一种名为TAB3的新蛋白的鉴定和表征，TAB3是一种与TAK1相关的TAB2样分子，可以激活类似于TAB2的NF-kappaB。内源性TAB3分别以IL-1依赖性和tnf依赖性的方式与TRAF6和TRAF2相互作用。此外，IL-1信号通过TRAF6导致TAB2和TAB3的泛素化。同时转染针对TAB2和TAB3的sirna可抑制IL-1和tnf诱导的TAK1和NF-kappaB的激活。这些结果表明，TAB2和TAB3在IL-1和TNF信号转导中作为TAK1激活的介质具有冗余功能。
The cytokines IL-1 and TNF induce expression of a series of genes that regulate inflammation through activation of NF-kappaB signal transduction pathways. TAK1, a MAPKKK, is critical for both IL-1- and TNF-induced activation of the NF-kappaB pathway. TAB2, a TAK1-binding protein, is involved in IL-1-induced NF-kappaB activation by physically linking TAK1 to TRAF6. However, IL-1-induced activation of NF-kappaB is not impaired in TAB2-deficient embryonic fibroblasts. Here we report the identification and characterization of a novel protein designated TAB3, a TAB2-like molecule that associates with TAK1 and can activate NF-kappaB similar to TAB2. Endogenous TAB3 interacts with TRAF6 and TRAF2 in an IL-1- and a TNF-dependent manner, respectively. Further more, IL-1 signaling leads to the ubiquitination of TAB2 and TAB3 through TRAF6. Cotransfection of siRNAs directed against both TAB2 and TAB3 inhibit both IL-1- and TNF-induced activation of TAK1 and NF-kappaB. These results suggest that TAB2 and TAB3 function redundantly as mediators of TAK1 activation in IL-1 and TNF signal transduction.