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

作者：Xue, Huiting; Liu, Lu; Zhao, Zihan; Zhang, Zhongyu; Guan, Yuan; Cheng, Hairong; Zhou, Yifa; Tai, Guihua^*

来源：Oncotarget, 2017, 8(30): 49824-49838.

DOI：10.18632/oncotarget.17760

• galectin-3
• apoptosis
• ERK
• ROS
• truncated protein

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.

• 出版日期2017-7-25
• 单位东北师范大学