The N-terminal tail coordinates with carbohydrate recognition domain to mediate galectin-3 induced apoptosis in T cells.
The N-terminal tail coordinates with carbohydrate recognition domain to mediate galectin-3 induced apoptosis in T cells.
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N端尾部与碳水化合物识别域协调介导galectin-3诱导的T细胞凋亡
DOI：
10.18632/oncotarget.17760
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发表时间：
2017-07-25
期刊：
影响因子：
--
通讯作者：
Tai G
中科院分区：
文献类型：
--
作者：
Xue H;Liu L;Zhao Z;Zhang Z;Guan Y;Cheng H;Zhou Y;Tai G
半乳糖凝集素-3是一种半乳糖凝集素，具有独特的柔性N-末端尾（NT），连接到保守的碳水化合物识别结构域（CRD）。半乳糖凝集素-3与肿瘤免疫耐受相关，并表现出诱导T细胞凋亡的能力。我们使用Jurkat，Jurkat E6-1和CEM T细胞系和人外周血单个核细胞（PBMC）来研究CRD和NT在诱导T细胞凋亡中的特异性作用。半乳糖凝集素-3触发持续的细胞外信号调节激酶（ERK）磷酸化，诱导细胞凋亡。ERK位于caspase-9的上游，独立地被活性氧（ROS）和蛋白激酶C（PKC）激活。前12个NT残基在凋亡中没有作用。残基13-68是激活ROS所必需的，但不激活PKC。然而，残基69-110是激活PKC所必需的。NT片段和NT特异性抗体拮抗全长半乳糖凝集素-3引发的细胞凋亡，进一步支持我们的研究结果。这些发现表明CRD和NT在诱导T细胞凋亡过程中起重要作用，这表明它们有可能作为逆转癌症免疫耐受的治疗靶点。
Galectin-3 is a galectin with a unique flexible N-terminal tail (NT) connected to the conserved carbohydrate recognition domain (CRD). Galectin-3 is associated with tumor immune tolerance and exhibits an ability to induce T cell apoptosis. We used Jurkat, Jurkat E6-1 and CEM T-cell lines and human peripheral blood mononuclear cells (PBMCs) to investigate the specific roles of the CRD and NT in inducing T cell apoptosis. Galectin-3 triggered sustained extracellular signal-regulated kinase (ERK) phosphorylation that induced apoptosis. ERK was situated upstream of caspase-9 and was independently activated by reactive oxygen species (ROS) and protein kinase C (PKC). The first twelve NT residues had no role in the apoptosis. Residues 13-68 were essential for activating ROS, but did not activate PKC. However, residues 69-110 were required for activation of PKC. An NT fragment and a NT-specific antibody antagonized the apoptosis triggered by full-length galectin-3 further supporting our findings. These findings indicate the CRD and NT play important roles during induction of T cell apoptosis, which suggests their potential as therapeutic targets for reversing cancer immune tolerance.
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DOI：
10.1158/1078-0432.ccr-12-2940
发表时间：
2013-04-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Chen C;Duckworth CA;Zhao Q;Pritchard DM;Rhodes JM;Yu LG
通讯作者：
Yu LG
影响因子：
9
作者：
通讯作者：
--
影响因子：
4.8
作者：
Jiang, XJ;Wang, XD
通讯作者：
Wang, XD
影响因子：
32.4
作者：
Demotte, Nathalie;Stroobant, Vincent;van der Bruggen, Pierre
通讯作者：
van der Bruggen, Pierre
影响因子：
4.8
作者：
Elad-Sfadia, G;Haklai, R;Kloog, Y
通讯作者：
Kloog, Y