The TFG protein, involved in oncogenic rearrangements, interacts with TANK and NEMO, two proteins involved in the NF-κB pathway
The TFG protein, involved in oncogenic rearrangements, interacts with TANK and NEMO, two proteins involved in the NF-κB pathway
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DOI：
10.1002/jcp.20644
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发表时间：
2006-07-01
影响因子：
5.6
通讯作者：
Greco, Angela
中科院分区：
文献类型：
--
作者：
Miranda, Claudia;Roccato, Emanuela;Greco, Angela
TRK融合基因（TFG）首先被确定为NTRK 1的伴侣，产生甲状腺TRK-T3癌基因，并且还参与与间变性淋巴瘤中的ALK和混合样软骨肉瘤中的NOR 1的致癌重排。TFG的生理作用仍然是未知的，但存在许多参与蛋白质相互作用的基序，这表明它可能通过与其他蛋白质结合而起作用。我们最近已经证明，TFG协会和调节酪氨酸磷酸酶SHP-1的活性。在这项研究中，通过酵母双杂交筛选，我们确定了NEMO和TANK，两个蛋白调节NF-κ B途径，作为新的TFG相互作用蛋白。这些相互作用在体外和体内进一步表征。我们提供的证据表明，TFG和NEMO可能是同一个高分子量复合物的一部分。TFG增强TNF-α、TANK、TNF受体相关因子（TRAF）2和TRAF 6诱导NF-κ B活性的作用。我们认为TFG是NF-κ B通路的新成员。
TRK-fused gene (TFG) was first identified as a partner of NTRK1 in generating the thyroid TRK-T3 oncogene, and is also involved in oncogenic rearrangements with ALK in anaplastic lymphoma and NOR1 in mixoid chondrosarcoma. The TFG physiological role is stil I unknown, but the presence of a number of motifs involved in protein interactions suggests that it may function by associating with other proteins. We have recently demonstrated that TFG associates and regulates the activity of the tyrosine phosphatase SHP-1. In this study by yeast two-hybrid screening we identified NEMO and TANK, two proteins modulating the NF-kappa B pathway, as novel TFG-interacting proteins. These interactions were further characterized in vitro and in vivo. We provide evidence that TFG and NEMO may be part of the same high molecular weight complex. TFG enhances the effect of TNF-alpha, TANK, TNF receptor-associated factor (TRAF)2, and TRAF6 in inducing NF-kappa B activity. We suggest that TFG is a novel member of the NF-kappa B pathway.