Fiche publication
Date publication
mars 2017
Journal
Cell death and differentiation
Auteurs
Membres identifiés du Cancéropôle Est :
Dr GARRIDO Carmen
,
Dr MICHEAU Olivier
,
Dr PICAUD Fabien
Tous les auteurs :
Dufour F, Rattier T, Shirley S, Picarda G, Constantinescu AA, Morlé A, Zakaria AB, Marcion G, Causse S, Szegezdi E, Zajonc DM, Seigneuric R, Guichard G, Gharbi T, Picaud F, Herlem G, Garrido C, Schneider P, Benedict CA, Micheau O
Lien Pubmed
Résumé
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.
Mots clés
Amino Acid Sequence, Animals, Apoptosis, drug effects, Cell Line, Cytomegalovirus, metabolism, Glycosylation, HCT116 Cells, Humans, Membrane Glycoproteins, genetics, Mice, Mutagenesis, Site-Directed, Nanoparticles, chemistry, Receptors, TNF-Related Apoptosis-Inducing Ligand, deficiency, Sequence Alignment, TNF-Related Apoptosis-Inducing Ligand, toxicity, Tunicamycin, toxicity, Viral Proteins, genetics
Référence
Cell Death Differ.. 2017 Mar;24(3):500-510
