title: Regulation of cell fate by lymphotoxin (LT) receptor signalling: Functional differences and similarities of the LT system to other TNF superfamily (TNFSF) members.
abstract: The role of TNFR family members in regulating cell fate both in the immune system and in non-lymphoid tissues has been under extensive research for decades. Moreover, the ability of several family members (death receptors) to induce death (mainly via apoptosis) represents a promising target for cancer therapy. Many studies have focused mostly on death receptors such as TNFRI, Fas and TRAIL-R due to their strong pro-apoptotic potential. Yet, cell death can be triggered via non-classical death receptors, and the lymphotoxin (LT) system represents a very good example of such a TNFR subfamily. Here we provide a comprehensive review of intracellular signalling pathways and cellular responses to LT-specific signalling, and compare for the first time the LT system to other TNFRs, such as CD40. Our aim is to highlight that non-classical TNFR-TNFL dyads such as the LT system demonstrate more complex, cell-type and context-specific capabilities. Understanding these complexities will permit a better understanding of the biological mechanisms via which non-death domain-containing TNFRs induce cell death, but may also allow the design of better therapeutic strategies.
authors.affiliation: Department of Biological Sciences, School of Applied Sciences, University of Huddersfield, Queensgate, Huddersfield HD13DH, UK.
authors.forename: Balid
authors.initials: B
authors.lastname: Albarbar
authors.affiliation: Department of Biological Sciences, School of Applied Sciences, University of Huddersfield, Queensgate, Huddersfield HD13DH, UK.
authors.forename: Christopher
authors.initials: C
authors.lastname: Dunnill
authors.affiliation: Department of Biological Sciences, School of Applied Sciences, University of Huddersfield, Queensgate, Huddersfield HD13DH, UK. Electronic address: N.Georgopoulos@hud.ac.uk.
authors.forename: Nikolaos T
authors.initials: NT
authors.lastname: Georgopoulos
mesh_terms: D000818:Animals; D017209:Apoptosis; D019013:CD40 Antigens / Q000276:immunology / Q000378:metabolism; D016923:Cell Death; D002454:Cell Differentiation; D006801:Humans; D008233:Lymphotoxin-alpha / Q000276:immunology / Q000378:metabolism*; D018124:Receptors, Tumor Necrosis Factor / Q000276:immunology / Q000378:metabolism; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000276:immunology / Q000378:metabolism*; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction; D048069:Tumor Necrosis Factors / Q000276:immunology / Q000378:metabolism
chemical_list: D019013:CD40 Antigens; D008233:Lymphotoxin-alpha; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; C415902:TNFRSF1B protein, human; D048069:Tumor Necrosis Factors
keywords: Apoptosis; CD40; Cell signalling; Lymphotoxin; Receptor cross-linking