Posttranslational Modifications and Death Receptor Signalling

2017 ◽  
pp. 247-290
Author(s):  
Olivier Micheau
Keyword(s):  
Posttranslational Modifications ◽  
Death Receptor ◽  
Receptor Signalling

scholarly journals Sweet modification and regulation of death receptor signalling pathway

2021 ◽  
Author(s):  
Kenta Moriwaki ◽  
Francis K M Chan ◽  
Eiji Miyoshi
Keyword(s):  
Critical Role ◽  
Immune Surveillance ◽  
Death Receptor ◽  
Death Receptors ◽  
Receptor Activation ◽  
Intracellular Signalling ◽  
Human Diseases ◽  
Tumour Necrosis Factor Receptor ◽  
Death Domain ◽  
Receptor Signalling

Abstract Death receptors, members of the tumour 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 signalling is regulated by various posttranslational 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 signalling proteins and regulate their functions. Here, we review the current understanding of glycan modifications of death receptor signalling and their impact on signalling activity.

Death receptors

2003 ◽  
Vol 39 ◽  
pp. 53-71 ◽  
Author(s):  
Harald Wajant
Keyword(s):  
Molecular Mechanisms ◽  
Ectodermal Dysplasia ◽  
Death Receptor ◽  
Growth Factor Receptor ◽  
Death Receptors ◽  
Tnf Receptor ◽  
Death Domain ◽  
Receptor Signalling ◽  
Death Receptor 3 ◽  
Necrosis Factor

Death receptors [Fas/Apo-1/CD95, TNF-R1 [tumour necrosis factor (TNF) receptor 1], DR3 [death receptor 3], TRAIL-R1 [TNF-related apoptosis-inducing ligand receptor 1], TRAIL-R2, DR6, p75-NGFR [p75-nerve growth factor receptor], EDAR [ectodermal dysplasia receptor]] form a subgroup of the TNF-R superfamily that can induce apoptosis (programmed cell death) via a conserved cytoplasmic signalling module termed the death domain. Although death receptors have been recognized mainly as apoptosis inducers, there is growing evidence that these receptors also fulfil a variety of nonapoptotic functions. This review is focused on the molecular mechanisms of apoptotic and non-apoptotic death receptor signalling in light of the phenotype of mice deficient in the various death receptors.

scholarly journals A type III effector antagonizes death receptor signalling during bacterial gut infection

Nature ◽  
2013 ◽  
Vol 501 (7466) ◽  
pp. 247-251 ◽  
Author(s):  
Jaclyn S. Pearson ◽  
Cristina Giogha ◽  
Sze Ying Ong ◽  
Catherine L. Kennedy ◽  
Michelle Kelly ◽  
...  
Keyword(s):  
Death Receptor ◽  
Type Iii Effector ◽  
Type Iii ◽  
Receptor Signalling

ERK controls epithelial cell death receptor signalling and cellular FLICE-like inhibitory protein (c-FLIP) in ulcerative colitis

2013 ◽  
Vol 91 (7) ◽  
pp. 839-849 ◽  
Author(s):  
Jakob Benedict Seidelin ◽  
Mehmet Coskun ◽  
Ben Vainer ◽  
Lene Riis ◽  
Christoffer Soendergaard ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Cell Death ◽  
Epithelial Cell ◽  
Protein C ◽  
Death Receptor ◽  
Inhibitory Protein ◽  
Receptor Signalling ◽  
Epithelial Cell Death ◽  
Cell Death Receptor

Clustering of death receptors in lipid rafts initiates neutrophil spontaneous apoptosis

2004 ◽  
Vol 32 (5) ◽  
pp. 679-681 ◽  
Author(s):  
D. Scheel-Toellner ◽  
K. Wang ◽  
L.K. Assi ◽  
P.R. Webb ◽  
R.M. Craddock ◽  
...  
Keyword(s):  
Lipid Rafts ◽  
Death Receptor ◽  
Death Receptors ◽  
Acid Sphingomyelinase ◽  
Early Event ◽  
Caspase 8 ◽  
Neutrophil Apoptosis ◽  
Receptor Signalling ◽  
Blocking Antibodies

Neutrophils die by apoptosis spontaneously within 12–24 h of their release from the bone marrow. The mechanism regulating entry of neutrophils into apoptosis at the end of their life-span is currently under debate. Our data suggest that neutrophil apoptosis involves a novel mechanism of caspase 8 activation that is indirectly regulated by accumulation of reactive oxygen species. We detected early activation of caspase 8 upstream of caspase 3 activation, suggesting death receptor signalling. The CD95 DISC (death-inducing signalling complex) was detected in neutrophils, but blocking antibodies to death receptors did not inhibit apoptosis, suggesting a novel mechanism for caspase 8 activation. Death receptor clustering in ceramide-rich lipid rafts is thought to be an early event in their signalling, so we investigated the role of ceramide generated by ASM (acid sphingomyelinase) in neutrophil apoptosis. Ceramide was generated early in neutrophil apoptosis, and ASM activity was required for neutrophil apoptosis. Moreover, neutrophil apoptosis was significantly delayed in ASM−/− mice compared with their wild-type littermates. CD95 DISC components were present in lipid rafts in neutrophils, and were progressively clustered in cultured neutrophils. Generation of ceramide was blocked by desferrioxamine, suggesting that hydroxyl radicals are important for the activation of ASM. This observation was in line with our earlier observation of a precipitous drop in reduced glutathione in the aging neutrophil.

scholarly journals FADD in Cancer: Mechanisms of Altered Expression and Function, and Clinical Implications

Cancers ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 1462 ◽  
Author(s):  
José L Marín-Rubio ◽  
Laura Vela-Martín ◽  
José Fernández-Piqueras ◽  
María Villa-Morales
Keyword(s):  
Posttranslational Modifications ◽  
Cell Cycle Control ◽  
Regulation Of Gene Expression ◽  
Death Receptor ◽  
Clinical Implications ◽  
Altered Expression ◽  
Cellular Processes ◽  
Potential Biomarker ◽  
And Function ◽  
And Control

FADD was initially described as an adaptor molecule for death receptor-mediated apoptosis, but subsequently it has been implicated in nonapoptotic cellular processes such as proliferation and cell cycle control. During the last decade, FADD has been shown to play a pivotal role in most of the signalosome complexes, such as the necroptosome and the inflammasome. Interestingly, various mechanisms involved in regulating FADD functions have been identified, essentially posttranslational modifications and secretion. All these aspects have been thoroughly addressed in previous reviews. However, FADD implication in cancer is complex, due to pleiotropic effects. It has been reported either as anti- or protumorigenic, depending on the cell type. Regulation of FADD expression in cancer is a complex issue since both overexpression and downregulation have been reported, but the mechanisms underlying such alterations have not been fully unveiled. Posttranslational modifications also constitute a relevant mechanism controlling FADD levels and functions in tumor cells. In this review, we aim to provide detailed, updated information on alterations leading to changes in FADD expression and function in cancer. The participation of FADD in various biological processes is recapitulated, with a mention of interesting novel functions recently proposed for FADD, such as regulation of gene expression and control of metabolic pathways. Finally, we gather all the available evidence regarding the clinical implications of FADD alterations in cancer, especially as it has been proposed as a potential biomarker with prognostic value.

scholarly journals Functional analysis of the posttranslational modifications of the death receptor 6

2009 ◽  
Vol 1793 (10) ◽  
pp. 1579-1587 ◽  
Author(s):  
Martin Klíma ◽  
Jitka Zájedová ◽  
Lenka Doubravská ◽  
Ladislav Anděra
Keyword(s):  
Functional Analysis ◽  
Posttranslational Modifications ◽  
Death Receptor ◽  
Death Receptor 6
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