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Micheau, Olivier

doi:10.1007/978-1-4419-0717-2_90

Cited by 1 publication

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“…However, unlike glycosylation or TRAIL antagonist receptors, downstream DISC components are not specific to TRAIL signaling. Most of them are also recruited to and regulate signal transduction induced by other receptors of the TNF superfamily [ 33 , 34 , 35 , 36 , 37 , 38 , 39 ] and beyond. An example of other such receptors are the toll-like receptors, including TLR3 [ 40 , 41 ].…”

Section: Membrane Proximal Trail Disc Formation and Signaling Regumentioning

confidence: 99%

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

Micheau

2018

IJMS

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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.

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