Publication

N-glycosylation of mouse trail-r and human trail-r1 enhances trail-induced death

Dufour, Florent
; 
Rattier, Thibault
; 
Shirley, Sarah
; 
Picarda, Gaelle
; 
Constantinescu, Andrei Alexandru
; 
Morlé, Aymeric
; 
Zakaria, Al Batoul
; 
Marcion, Guillaume
; 
Causse, Sebastien
; 
Szegezdi, Eva
... show 10 more
Identifiers
http://hdl.handle.net/10379/11286
 https://doi.org/10.13025/25016
Publication Date
2017-02-10
Keywords
cancer-cells, human cytomegalovirus, carcinoma cells, receptor, apoptosis, galectin-3, apo2l/trail, sialylation, sensitivity, induction
Type
Article
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Citation
Dufour, Florent; Rattier, Thibault; Shirley, Sarah; Picarda, Gaelle; Constantinescu, Andrei Alexandru; Morlé, Aymeric; Zakaria, Al Batoul; Marcion, Guillaume; Causse, Sebastien; Szegezdi, Eva; Zajonc, Dirk Michael; Seigneuric, Renaud; Guichard, Gilles; Gharbi, Tijani; Picaud, Fabien; Herlem, Guillaume; Garrido, Carmen; Schneider, Pascal; Benedict, Chris Alan; Micheau, Olivier (2017). N-glycosylation of mouse trail-r and human trail-r1 enhances trail-induced death. Cell Death and Differentiation 24 (3), 500-510
Abstract
APO2L/TRAIL (TNF-related apoptosis-inducing ligand) induces death of tumor cells through two agonist receptors, TRAIL-R1 and TRAIL-R2. We demonstrate here that N-linked glycosylation (N-glyc) plays also an important regulatory role for TRAIL-R1-mediated and mouse TRAIL receptor (mTRAIL-R)-mediated apoptosis, but not for TRAIL-R2, which is devoid of N-glycans. Cells expressing N-glyc-defective mutants of TRAIL-R1 and mouse TRAIL-R were less sensitive to TRAIL than their wild-type counterparts. Defective apoptotic signaling by N-glyc-deficient TRAIL receptors was associated with lower TRAIL receptor aggregation and reduced DISC formation, but not with reduced TRAIL-binding affinity. Our results also indicate that TRAIL receptor N-glyc impacts immune evasion strategies. The cytomegalovirus (CMV) UL141 protein, which restricts cell-surface expression of human TRAIL death receptors, binds with significant higher affinity TRAIL-R1 lacking N-glyc, suggesting that this sugar modification may have evolved as a counterstrategy to prevent receptor inhibition by UL141. Altogether our findings demonstrate that N-glyc of TRAIL-R1 promotes TRAIL signaling and restricts virus-mediated inhibition.
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Publisher
Springer Nature
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Attribution-NonCommercial-NoDerivs 3.0 Ireland
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Externally hosted open access publications with University of Galway authors (2)