Next Article in Journal
Molecular Evolution of Chloroplast Genomes of Orchid Species: Insights into Phylogenetic Relationship and Adaptive Evolution
Next Article in Special Issue
The Modulatory Roles of N-glycans in T-Cell-Mediated Autoimmune Diseases
Previous Article in Journal
Comparative Transcriptome Profiling of Rice Near-Isogenic Line Carrying Xa23 under Infection of Xanthomonas oryzae pv. oryzae
Previous Article in Special Issue
Glycosylation as a Main Regulator of Growth and Death Factor Receptors Signaling
Article Menu
Issue 3 (March) cover image

Export Article

Open AccessReview
Int. J. Mol. Sci. 2018, 19(3), 715; https://doi.org/10.3390/ijms19030715

Regulation of TNF-Related Apoptosis-Inducing Ligand Signaling by Glycosylation

1
INSERM, UMR1231, Laboratoire d’Excellence LipSTIC, F-21079 Dijon, France
2
UFR Sciences de Santé, University Bourgogne Franche-Comté, UBFC, F-21079 Dijon, France
Received: 1 February 2018 / Revised: 19 February 2018 / Accepted: 24 February 2018 / Published: 2 March 2018
(This article belongs to the Special Issue Glycosylation and Glycoproteins 2017)
Full-Text   |   PDF [10233 KB, uploaded 2 March 2018]   |  

Abstract

Tumor necrosis-factor related apoptosis-inducing ligand, also known as TRAIL or APO2L (Apo-2 ligand), is a cytokine of the TNF superfamily acknowledged for its ability to trigger selective apoptosis in tumor cells while being relatively safe towards normal cells. Its binding to its cognate agonist receptors, namely death receptor 4 (DR4) and/or DR5, can induce the formation of a membrane-bound macromolecular complex, coined DISC (death-signaling inducing complex), necessary and sufficient to engage the apoptotic machinery. At the very proximal level, TRAIL DISC formation and activation of apoptosis is regulated both by antagonist receptors and by glycosylation. Remarkably, though, despite the fact that all membrane-bound TRAIL receptors harbor putative glycosylation sites, only pro-apoptotic signaling through DR4 and DR5 has, so far, been found to be regulated by N- and O-glycosylation, respectively. Because putative N-glycosylation sequons and O-glycosylation sites are also found and conserved in all these receptors throughout all animal species (in which these receptors have been identified), glycosylation is likely to play a more prominent role than anticipated in regulating receptor/receptor interactions or trafficking, ultimately defining cell fate through TRAIL stimulation. This review aims to present and discuss these emerging concepts, the comprehension of which is likely to lead to innovative anticancer therapies. View Full-Text
Keywords: TRAIL; death-receptor; ligand; glycosylation; apoptosis; galectin; aggregation; trafficking; evolution; carbohydrate binding proteins; DR4; DR5; DcR1; DcR2; TRAIL-R1; TRAIL-R2; TRAIL-R3; TRAIL-R4; TNFRSF10A; TNFRSF10B; TNFRSF10C; TNFRSF10D TRAIL; death-receptor; ligand; glycosylation; apoptosis; galectin; aggregation; trafficking; evolution; carbohydrate binding proteins; DR4; DR5; DcR1; DcR2; TRAIL-R1; TRAIL-R2; TRAIL-R3; TRAIL-R4; TNFRSF10A; TNFRSF10B; TNFRSF10C; TNFRSF10D
Figures

Graphical abstract

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
SciFeed

Share & Cite This Article

MDPI and ACS Style

Micheau, O. Regulation of TNF-Related Apoptosis-Inducing Ligand Signaling by Glycosylation. Int. J. Mol. Sci. 2018, 19, 715.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top