TWE-PRIL; a fusion protein of TWEAK and APRIL

Kolfschoten, Geertruida M.; Pradet‐Balade, Bérengère; Hahne, Michael; Medema, Jan Paul

doi:10.1016/s0006-2952(03)00493-3

Cited by 35 publications

(25 citation statements)

References 60 publications

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“…Previously, we detected TWE-PRIL on monocytes, T cells (40,51), and dendritic cells (unpublished results), which might suggest a balance between cell surface-expressed (TWE-PRIL), secreted, and ECMbound ligand (APRIL). That many TNF family ligands require cross-linking for an effective signal has been well described (52,53).…”

Section: Discussionmentioning

confidence: 64%

The proteoglycan (heparan sulfate proteoglycan) binding domain of APRIL serves as a platform for ligand multimerization andcross‐linking

et al. 2009

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A proliferation-inducing ligand (APRIL) (also known as TALL-2 and TRDL-1) is a member of the tumor necrosis factor (TNF) superfamily that has tumorigenic properties but is also important for the induction of humoral immune responses. APRIL binds two TNF receptors: transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI) and B-cell maturation antigen (BCMA) as well as heparan sulfate proteoglycans (HSPGs). The aim of this study was to clarify the role of the HSPG interaction in canonical APRIL signaling, because it has been proposed to act as a docking site and also to play a role in direct signaling. In this study, we generated point mutants of soluble APRIL that lack either the capacity to bind HSPGs or TACI and BCMA and then tested the function of these mutants in mouse B-cell assays. In contrast to previous reports, we found that APRIL alone is sufficient to costimulate B-cell proliferation and drive IgA production and does not require artificial antibody cross-linking. We found no evidence that APRIL requires signaling through HSPGs but, notably, were able to show that binding of APRIL to HSPGs is crucial for mediating natural APRIL cross-linking to allow for optimal activation of murine B cells.

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Section: Discussionmentioning

confidence: 64%

The proteoglycan (heparan sulfate proteoglycan) binding domain of APRIL serves as a platform for ligand multimerization andcross‐linking

et al. 2009

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“…The gene for APRIL is located 1 Kb downstream from the gene encoding for TWEAK in chromosome 17 in humans. A transmembrane protein consisting of the intracellular and transmembrane region of TWEAK fused to the APRIL receptor binding site has been described as TWE-PRIL in human lymphocytes and monocytes [13,16]. The biological function of this fusion protein is still unknown.…”

Section: Tweak and Fn14 Structure And Expressionmentioning

confidence: 99%

TWEAK and the Central Nervous System

Yepes

2007

Mol Neurobiol

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Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) is a member of the tumor necrosis factor superfamily that acts on responsive cells via binding to a cell surface receptor named fibroblast growth factor-inducible 14 (Fn14). TWEAK can regulate numerous cellular responses in vitro and in vivo. Recent studies have indicated that TWEAK and Fn14 are expressed in the central nervous system (CNS), and that in response to a variety of stimuli, including cerebral ischemia, there is an increase in TWEAK and Fn14 expression in perivascular astrocytes, microglia, endothelial cells, and neurons with subsequent increase in the permeability of the blood-brain barrier (BBB) and cell death. Furthermore, there is a growing body of evidence indicating that TWEAK induces the activation of the NF-kappaB in the CNS with release of proinflammatory cytokines and matrix metalloproteinases. In addition, inhibition of TWEAK activity by either treatment with a Fn14-Fc fusion protein or neutralizing anti-TWEAK antibodies has shown therapeutic efficacy in animal models of ischemic stroke, cerebral edema, and multiple sclerosis.

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“…APRIL functions as a soluble factor in mammals, and is also expressed as a cell surface fusion protein with TWEAK called TWE-PRIL (19, 20). In humans and mice APRIL is flanked upstream by TWEAK and downstream by Smt3ip1 / Senp-3 , a member of the sentrin/SUMO specific protease family, (21).…”

Section: Introductionmentioning

confidence: 99%

Characterization of Lamprey BAFF-like Gene: Evolutionary Implications

Das

Sutoh

Hirano

et al. 2016

The Journal of Immunology

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BAFF (TNFSF13B/Blys) and APRIL (TNFSF13), are important regulatory factors for lymphocyte activation and survival in mammals. A BAFF/APRIL-like relative called BALM has also been identified in cartilaginous and bony fishes, and we report here a BAFF-like gene in lampreys. Our phylogenetic analysis of these genes, and a related TNFSF12 gene called TWEAK, suggest that, whereas an ancestral homologue of BAFF and APRIL was already present in a common ancestor of jawed and jawless vertebrates, TWEAK evolved early on in the jawed vertebrate lineage. Like mammalian BAFF and APRIL, the lamprey BAFF-like gene is expressed in T-like, B-like and innate immune cells. The predicted protein encoded by this BAFF-like gene in lampreys exhibits higher sequence similarity with mammalian BAFF than APRIL. Correspondingly, we find BAFF orthologues in all of the jawed vertebrate representatives that we examined, although APRIL and/or BALM orthologues are not identifiable in certain jawed vertebrates. For example, BALM is not identifiable in tetrapods, and APRIL is not identifiable in several bony fishes or in birds, the latter of which also lack a TWEAK-like gene. Our analysis further suggests that a hybrid molecule called TWE-PRIL, which is a product of an in-genomic fusion between APRIL and TWEAK genes evolved early in mammalian evolution.

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TWE-PRIL; a fusion protein of TWEAK and APRIL

Cited by 35 publications

References 60 publications

The proteoglycan (heparan sulfate proteoglycan) binding domain of APRIL serves as a platform for ligand multimerization andcross‐linking

The proteoglycan (heparan sulfate proteoglycan) binding domain of APRIL serves as a platform for ligand multimerization andcross‐linking

TWEAK and the Central Nervous System

Characterization of Lamprey BAFF-like Gene: Evolutionary Implications

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