TY - JOUR
T1 - N-glycosylation of mouse TRAIL-R and human TRAIL-R1 enhances TRAIL-induced death
AU - Dufour, Florent
AU - Rattier, Thibault
AU - Shirley, Sarah
AU - Picarda, Gaelle
AU - Constantinescu, Andrei Alexandru
AU - Morlé, Aymeric
AU - Zakaria, Al Batoul
AU - Marcion, Guillaume
AU - Causse, Sebastien
AU - Szegezdi, Eva
AU - Zajonc, Dirk Michael
AU - Seigneuric, Renaud
AU - Guichard, Gilles
AU - Gharbi, Tijani
AU - Picaud, Fabien
AU - Herlem, Guillaume
AU - Garrido, Carmen
AU - Schneider, Pascal
AU - Benedict, Chris Alan
AU - Micheau, Olivier
N1 - Publisher Copyright:
© The Author(s) 2017.
PY - 2017/3/1
Y1 - 2017/3/1
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/85012195533
U2 - 10.1038/cdd.2016.150
DO - 10.1038/cdd.2016.150
M3 - Article
SN - 1350-9047
VL - 24
SP - 500
EP - 510
JO - Cell Death and Differentiation
JF - Cell Death and Differentiation
IS - 3
ER -
