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Open AccessJournal ArticleDOI

Induction of apoptosis and activation of NF-κB by CD95 require different signalling thresholds

TLDR
It is demonstrated that induction of apoptosis requires two wild‐type alleles of CD95, at the same time allowing induction of survival or proliferative pathways, which could contribute to the increased risk for lymphoma seen in ALPS type Ia patients.
Abstract
Mutations in the death domain of the death receptor CD95 (APO-1/Fas) cause lymphoproliferation and autoimmune disease in both lprcg mice and in patients with autoimmune lymphoproliferative syndrome (ALPS) type Ia. By testing lymphocytes from ALPS type Ia patients, comparing heterozygous with homozygous lprcg mice and coexpressing wild-type and mutant CD95 receptors, we demonstrate that induction of apoptosis requires two wild-type alleles of CD95. By contrast, nuclear factor-κB (NF-κB) can be fully activated in cells expressing both a mutant and a wild-type CD95 allele, suggesting different thresholds to activate the two signalling pathways. This was confirmed by testing lymphocytes from heterozygous lpr mice, which showed reduced sensitivity to CD95-mediated apoptosis but normal activation of NF-κB when compared with wild-type mice. Mutations in CD95 may eliminate the tumour-suppressive function of CD95, at the same time allowing induction of survival or proliferative pathways, which could contribute to the increased risk for lymphoma seen in ALPS type Ia patients.

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Journal ArticleDOI

Fas/CD95 Signaling Pathway in Damage-Associated Molecular Pattern (DAMP)-Sensing Receptors

TL;DR: Some of the molecular links that might connect the CD95 signaling to DAMP sensors and contribute to the pro-inflammatory role of CD95 and favor cancer development or severity of chronic inflammatory and auto-immune disorders are discussed.

Regulation of apoptosis during treatment and resistance development in tumour cells

TL;DR: Induction of apoptosis is the most studied cell death process and it is a tightly regulated physiological event that enables elimination of damaged and unwanted cells.
Journal ArticleDOI

FAS (Fas cell surface death receptor)

TL;DR: CD95 (also known as Fas) is a death receptor that belongs to the TNF-receptor superfamily that implements both apoptotic and non-apoptotic signalling pathways.
Journal ArticleDOI

CD95 gene deletion may reduce clonogenic growth and invasiveness of human glioblastoma cells in a CD95 ligand-independent manner

TL;DR: In this article , the authors characterized CD95 and CD95L expression in human glioma-initiating cells (GIC), a glioblastoma cell population with stem cell features, and investigated the consequences of CRISPR-Cas9-mediated CD95 or CD95l gene deletion.
Dissertation

La modulation de l'apoptose dépendante du récepteur Fas : étude des évènements précoces de la voie de signalisation apoptotique dans un modèle de lymphocytes T humains

TL;DR: It is shown that the specific down-regulation of c-FLIP restored the Fas-mediated signal in these mutated cells and it was observed that the P13K signaling pathway maintains Fas excluded from the lipid rafts.
References
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Journal ArticleDOI

Dominant interfering Fas gene mutations impair apoptosis in a human autoimmune lymphoproliferative syndrome

TL;DR: The occurrence of Fas mutations together with abnormal T cell apoptosis in ALPS patients suggests an involvement of Fas in this recently recognized disorder of lymphocyte homeostasis and peripheral self-tolerance.

Mutations inFasAssociated withHuman Lymphoproliferative Syndrome and Autoimmunity

TL;DR: Fas expression and function were analyzed in three children with a lymphoproliferative syndrome and may provide a molecular basis for some autoimmune diseases in humans.
Journal ArticleDOI

Mutations in Fas associated with human lymphoproliferative syndrome and autoimmunity

TL;DR: Fas expression and function were analyzed in three children (including two siblings) with a lymphoproliferative syndrome, two of whom also had autoimmune disorders as discussed by the authors, showing that a large deletion in the gene encoding Fas and no detectable cell surface expression characterized the most affected patient.
Journal ArticleDOI

The CD95(APO-1/Fas) DISC and beyond

TL;DR: A number of proteins have been reported to regulate formation or activity of the DISC, the complex of proteins that forms upon triggering of CD95 that is essential for induction of apoptosis.
Journal ArticleDOI

Fas Preassociation Required for Apoptosis Signaling and Dominant Inhibition by Pathogenic Mutations

TL;DR: Results show that formation of preassociated receptor complexes is necessary for Fas signaling and dominant interference in human disease.
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