Sweet modification and regulation of death receptor signaling pathway

Death receptors, members of the tumor necrosis factor receptor (TNFR) superfamily, are characterized by the presence of a death domain in the cytosolic region. TNFR1, Fas, and TNF-related apoptosis-inducing ligand receptors, which are prototypical death receptors, exert pleiotropic functions in cell death, inflammation, and immune surveillance. Hence, they are involved in several human diseases. The activation of death receptors and downstream intracellular signaling are regulated by various post-translational modifications, such as phosphorylation, ubiquitination, and glycosylation. Glycosylation is one of the most abundant and versatile modifications to proteins and lipids, and it plays a critical role in the development and physiology of organisms, as well as the pathology of many human diseases. Glycans control a number of cellular events, such as receptor activation, signal transduction, endocytosis, cell recognition, and cell adhesion. It has been demonstrated that oligo- and monosaccharides modify death receptors and intracellular signaling proteins, and regulate their functions. Here, we review the current understanding of glycan modifications of death receptor signaling and their impact on signaling activity.