Oncotarget

Research Papers:

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

Huiting Xue, Lu Liu, Zihan Zhao, Zhongyu Zhang, Yuan Guan, Hairong Cheng, Yifa Zhou and Guihua Tai _

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Oncotarget. 2017; 8:49824-49838. https://doi.org/10.18632/oncotarget.17760

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Abstract

Huiting Xue1, Lu Liu1, Zihan Zhao1, Zhongyu Zhang1, Yuan Guan1, Hairong Cheng1, Yifa Zhou1 and Guihua Tai1

1School 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 important roles during induction of T cell apoptosis, which suggests their potential as therapeutic targets for reversing cancer immune tolerance.


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