Wei Jingguang, Zhang Ping, Guo Minglan, Xu Meng, Li Pengfei, Chen Xiuli, Gao Pin, Yan Yang, Wei Shina, Qin Qiwei
Key Laboratory of Tropical Marine Bio-resources and Ecology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou 510301, PR China; Guangdong Provincial Key Laboratory of Applied Marine Biology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou 510301, PR China.
Teaching Center of Biology Experiment, School of Life Sciences, Sun Yat-sen University, 135West Xingang Road, Guangzhou 510275, PR China.
Fish Shellfish Immunol. 2015 Oct;46(2):274-84. doi: 10.1016/j.fsi.2015.07.006. Epub 2015 Jul 11.
TTRAP (TRAF and TNF receptor-associated protein) is latest identified cytosolic protein that serves as a negative regulator for TNF signaling pathway. In this study, a member of TNF superfamily, TTRAP gene (designed as EcTTRAP) was cloned from grouper, Epinephelus coioides. There was an Exo_endo_phos type domain in EcTTRAP, and it was well conserved when compared with other TTRAPs, especially the endonuclease activity related motifs. EcTTRAP exhibited prominent endonuclease activity against the genome DNA from Escherichia coli, Vibrio vulnificus and E. coli JM109. Intracellular localization revealed that EcTTRAP expression distributed in both cytoplasm and nucleus. Real-time PCR analysis indicates that EcTTRAP is expressed in all selective grouper tissues, with the higher expression level in muscle, skin and gills. EcTTRAP was identified as a remarkably (P < 0.01) up-regulated protein responding to Singapore grouper iridovirus (SGIV) infection. Overexpression of EcTTRAP inhibited NF-κB activation, meanwhile the C terminal portion of the protein was found to be responsive domain for the inhibition. Stable transfection of FHM cells with EcTTRAP inhibited apoptosis induced by SGIV. Overexpression of EcTTRAP in grouper spleen (GS) cells inhibited the replication of SGIV. The present results provided new evidences for the potential roles of such molecule in E. coioides, and further confirmed the existence of TTRAP modulated TNF signaling pathway in grouper.
TTRAP(TRAF与肿瘤坏死因子受体相关蛋白)是最新鉴定出的胞质蛋白,它作为肿瘤坏死因子信号通路的负调节因子。在本研究中,从斜带石斑鱼(Epinephelus coioides)中克隆了肿瘤坏死因子超家族的一个成员TTRAP基因(命名为EcTTRAP)。EcTTRAP中存在一个Exo_endo_phos型结构域,与其他TTRAP相比,它具有高度保守性,尤其是与核酸内切酶活性相关的基序。EcTTRAP对大肠杆菌、创伤弧菌和大肠杆菌JM109的基因组DNA表现出显著的核酸内切酶活性。细胞内定位显示EcTTRAP表达分布于细胞质和细胞核中。实时PCR分析表明,EcTTRAP在所有选定的石斑鱼组织中均有表达,在肌肉、皮肤和鳃中的表达水平较高。EcTTRAP被鉴定为对新加坡石斑鱼虹彩病毒(SGIV)感染有显著上调(P < 0.01)的蛋白。EcTTRAP的过表达抑制了NF-κB的激活,同时发现该蛋白的C末端部分是抑制的反应结构域。用EcTTRAP稳定转染FHM细胞可抑制SGIV诱导的细胞凋亡。EcTTRAP在石斑鱼脾脏(GS)细胞中的过表达抑制了SGIV的复制。本研究结果为该分子在斜带石斑鱼中的潜在作用提供了新的证据,并进一步证实了石斑鱼中存在TTRAP调节的肿瘤坏死因子信号通路。