The N-terminal tail coordinates with carbohydrate recognition domain to mediate galectin-3 induced apoptosis in T cells

作者：Huiting Xue, Lu Liu, Zihan Zhao, Zhongyu Zhang, Yuan Guan, Hairong Cheng, Yifa Zhou, Guihua Tai · 发表于：Oncotarget · 年份：2017 · DOI：10.18632/oncotarget.17760 · 被引用次数：43 · 研究领域：Galectins and Cancer Biology、Aluminum Alloys Composites Properties

// Huiting Xue 1 , Lu Liu 1 , Zihan Zhao 1 , Zhongyu Zhang 1 , Yuan Guan 1 , Hairong Cheng 1 , Yifa Zhou 1 and Guihua Tai 1 1 School of Life Sciences, Northeast Normal University, Changchun, China Correspondence to: Guihua Tai, email: taigh477@nenu.edu.cn Keywords: galectin-3, apoptosis, ERK, ROS, truncated protein Received: September 12, 2016     Accepted: April 24, 2017     Published: May 10, 2017 ABSTRACT 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...