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CD95L

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https://www.readbyqxmd.com/read/28300842/cd95-ligand-induces-senescence-in-mismatch-repair-deficient-human-colon-cancer-via-chronic-caspase-mediated-induction-of-dna-damage
#1
Danielle A Raats, Nicola Frenkel, Susanne J van Schelven, Inne HMBorel Rinkes, Jamila Laoukili, Onno Kranenburg
CD95 is best known for its ability to induce apoptosis via a well-characterized pathway involving caspase-mediated proteolytic events. However, in apoptosis-resistant cell lines of diverse cancer types stimulation of CD95 primarily has pro-tumorigenic effects that affect many of the hallmarks of cancer. For instance, in colon cancer cells with a mutant KRAS gene CD95 primarily promotes invasion and metastasis. In the current study, we further investigated the context dependency of the consequences of CD95 activation in colon cancer...
March 16, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28273453/cd95-fas-increases-stemness-in-cancer-cells-by-inducing-a-stat1-dependent-type-i-interferon-response
#2
Abdul S Qadir, Paolo Ceppi, Sonia Brockway, Calvin Law, Liang Mu, Nikolai N Khodarev, Jung Kim, Jonathan C Zhao, William Putzbach, Andrea E Murmann, Zhuo Chen, Wenjing Chen, Xia Liu, Arthur R Salomon, Huiping Liu, Ralph R Weichselbaum, Jindan Yu, Marcus E Peter
Stimulation of CD95/Fas drives and maintains cancer stem cells (CSCs). We now report that this involves activation of signal transducer and activator of transcription 1 (STAT1) and induction of STAT1-regulated genes and that this process is inhibited by active caspases. STAT1 is enriched in CSCs in cancer cell lines, patient-derived human breast cancer, and CD95(high)-expressing glioblastoma neurospheres. CD95 stimulation of cancer cells induced secretion of type I interferons (IFNs) that bind to type I IFN receptors, resulting in activation of Janus-activated kinases, activation of STAT1, and induction of a number of STAT1-regulated genes that are part of a gene signature recently linked to therapy resistance in five primary human cancers...
March 7, 2017: Cell Reports
https://www.readbyqxmd.com/read/28223543/role-of-caspases-in-cd95-induced-biphasic-activation-of-acid-sphingomyelinase
#3
Mario Stephan, Bärbel Edelmann, Supandi Winoto-Morbach, Ottmar Janssen, Uwe Bertsch, Cristiana Perrotta, Stefan Schütze, Jürgen Fritsch
Acid sphingomyelinase (A-SMase) plays an important role in the initiation of CD95 signaling by forming ceramide-enriched membrane domains that enable clustering and activation of the death receptors. In TNF-R1 and TRAIL-R1/R2 signaling, A-SMase also contributes to the lysosomal apoptosis pathway triggered by receptor internalization. Here, we investigated the molecular mechanism of CD95-mediated A-SMase activation, demonstrating that A-SMase is located in internalized CD95-receptosomes and is activated by the CD95/CD95L complex in a biphasic manner...
March 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28149915/myeloid-derived-suppressor-cell-arginase-1-il-17-and-cl-cd95l-an-explosive-cocktail-in-lupus
#4
COMMENT
Robin J Flynn, Patrick Legembre
No abstract text is available yet for this article.
December 2016: Annals of Translational Medicine
https://www.readbyqxmd.com/read/28078597/cd95-and-the-mrl-lpr-mouse-model
#5
Robin J Flynn
CD95 (Fas-ligand) is a key mediator of cell death in multiple setting, thus its loss within the MRL-lpr (Fas(lpr)) homozygote mice results in spontaneous autoimmunity. This is characterized by the development of arthritis and immune complex glomerulonephrosis making this strain a useful model for studying systemic lupus erythematosus. Herein we describe a method to exploit the heterozygote offspring of this strain in a model to study the effects of a CD95L blocking peptide on lupus-like disease in vivo.
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28078596/liquid-chromatography-high-resolution-mass-spectrometry-method-to-study-sphingolipid-metabolism-changes-in-response-to-cd95l
#6
Fatima Bilal, Michaël Pérès, Pauline Le Faouder, Aude Dupuy, Justine Bertrand-Michel, Nathalie Andrieu-Abadie, Thierry Levade, Bassam Badran, Ahmad Daher, Bruno Ségui
Sphingolipids are sphingoid base-containing lipids, among which some metabolites behave as bioactive molecules in various biological processes, including cell death. Whereas ceramide is now viewed as an anti-oncometabolite, leading to cancer cell death, CD95L-induced apoptosis is associated with sphingolipid changes, which likely contribute to caspase-dependent signaling pathway activation. Here, we describe Liquid Chromatography-high resolution mass spectrometry method (LC-HRMS) to analyze sphingolipid metabolism changes triggered by CD95L...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28078595/method-to-measure-sphingomyelin-synthase-activity-changes-in-response-to-cd95l
#7
Fatima Bilal, Michaël Pérès, Nathalie Andrieu-Abadie, Thierry Levade, Bassam Badran, Ahmad Daher, Bruno Ségui
Sphingomyelin synthases 1 and 2 convert the anti-oncometabolite ceramide to sphingomyelin, the most abundant sphingolipid in plasma membrane. CD95L-induced ceramide increase is associated with the caspase-dependent inhibition of sphingomyelin synthesis, which enhances the mitochondrial route to apoptosis. Knocking down sphingomyelin synthase 1 or inhibiting sphingomyelin synthesis facilitates ceramide accumulation, cytochrome c release from mitochondria, and caspase-9 activation in cancer cell upon CD95L treatment...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28078590/quantifying-cd95-cl-cd95l-implications-in-cell-mechanics-and-membrane-tension-by-atomic-force-microscopy-based-force-measurements
#8
Anaïs Sadoun, Pierre-Henri Puech
Atomic force microscopy (AFM) is an invaluable tool to investigate the structure of biological material surfaces by imaging them at nanometer scale in physiological conditions. It can also be used to measure the forces and mechanics from single molecule interaction to cell-cell adhesion. Here, we present a methodology that allows to quantify cell elastic properties (using the Young modulus) and cell membrane tension modulated by CD95/cl-CD95L interactions by coupling nanoindentation and membrane tube pulling using suitably decorated AFM levers...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28078588/boyden-chamber-assay-to-study-of-cell-migration-induced-by-metalloprotease-cleaved-cd95l
#9
Amanda Poissonnier, Patrick Legembre
CD95 receptor, also called Fas or Apo-1, is a member of the tumor necrosis factor receptors (TNF-R) superfamily (Itoh and Nagata, J Biol Chem 268:10932-10937, 1993). Its cognate ligand, CD95L, is a transmembrane cytokine, which can be cleaved by metalloproteases (Matsuno et al., J Rheumatol 28:22-28, 2001; Vargo-Gogola et al., Arch Biochem Biophys 408:155-161, 2002; Kiaei et al., Exp Neurol 205:74-81, 2007; Schulte et al., Cell Death Differ 14:1040-1049, 2007) releasing a soluble ligand into the bloodstream...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28078583/generation-and-application-of-bioluminescent-cd95-ligand-fusion-proteins
#10
Isabell Lang, Juliane Kums, Harald Wajant
The quantitative evaluation of the interaction of soluble CD95L with CD95 is not only important for a detailed understanding of CD95 biology but is also of special relevance for the characterization and development of inhibitors of this interaction. The assembly of a CD95L-CD95 complex capable to recruit intracellular factors not only involves pre-assembly of CD95 molecules in the absence of CD95L but is also modulated by cellular factors such as interaction with the actin cytoskeleton and plasma membrane compartmentation of CD95...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28078582/fluorometric-methods-for-detection-of-mitochondrial-membrane-depolarization-induced-by-cd95-activation
#11
Kenji F Shoji, Laure Debure
Mitochondria are key organelles implicated in energy supply and apoptosis. Therefore, tracking mitochondria and measuring their membrane potential is of crucial interest to monitor the CD95-mediated apoptotic signal. In this chapter, we report how we evaluate the drop of the mitochondrial transmembrane potential in leukemic cells and adherent triple negative breast cancer cells exposed to cytotoxic CD95L. We describe a simple, robust, and well-established protocol using classical fluorescent probes, DIOC6(3) and TMRM...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28078581/proximity-ligation-assay-pla-to-evaluate-disc-and-misc-composition
#12
Melissa Thomas, Patrick Legembre
Distribution of the death receptor CD95 into lipid rafts (aggregation) and/or its internalization may contribute to the implementation of the apoptotic signal at the detriment of the non-apoptotic signaling pathway [1-6]. Also CD95 can form different protein complexes via dynamic protein-protein interactions (PPIs) according to its interaction with soluble or transmembrane CD95L. Therefore, spatiotemporal identification of these PPIs is pivotal to anticipate the signaling pathway implemented in cells stimulated with different forms of CD95L...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28078578/cd95-stimulation-with-cd95l-and-disc-analysis
#13
Matthieu Le Gallo, Patrick Legembre
CD95 and its ligand CD95L play a major role in immune surveillance and homeostasis. CD95L is expressed by activated T lymphocytes and NK cells to induce apoptosis in cancer and virus-infected cells. The goal of this chapter is to describe a method used to immunoprecipitate CD95 and analyze its associated protein complex in cells stimulated with a cytotoxic CD95L (i.e., Ig-CD95L).
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28078577/production-of-the-non-apoptotic-metalloprotease-cleaved-cd95l-and-its-cytotoxic-recombinant-counterpart-designed-ig-cd95l
#14
Eléonore Lepvrier, Sophie Martin, Brigitte Collet
The ligand of CD95, CD95L (also known as FasL or CD178), is a type II transmembrane protein that belongs to the Tumor Necrosis factor (TNF) family (Fig. 1a). This membrane-bound cytokine is mainly expressed at the surface of activated T lymphocytes and natural killer cells, where it is used as an apoptotic factor to eliminate infected and transformed cells (Strasser et al., Immunity 30:180-192, 2009).
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28052242/c-flip-expression-in-foxp3-expressing-cells-is-essential-for-survival-of-regulatory-t-cells-and-prevention-of-autoimmunity
#15
Carlos Plaza-Sirvent, Marc Schuster, Yvonne Neumann, Ulrike Heise, Marina C Pils, Klaus Schulze-Osthoff, Ingo Schmitz
Regulatory T (Treg) cells are critical for the shutdown of immune responses and have emerged as valuable targets of immunotherapies. Treg cells can rapidly proliferate; however, the homeostatic processes that limit excessive Treg cell numbers are poorly understood. Here, we show that, compared to conventional T cells, Treg cells have a high apoptosis rate ex vivo correlating with low c-FLIP expression. Treg-specific deletion of c-FLIP in mice resulted in fatal autoimmune disease of a scurfy-like phenotype characterized by absent peripheral Treg cells, activation of effector cells, multi-organ immune cell infiltration, and premature death...
January 3, 2017: Cell Reports
https://www.readbyqxmd.com/read/28004776/a20-curtails-primary-but-augments-secondary-cd8-t-cell-responses-in-intracellular-bacterial-infection
#16
Sissy Just, Gopala Nishanth, Jörn H Buchbinder, Xu Wang, Michael Naumann, Inna Lavrik, Dirk Schlüter
The ubiquitin-modifying enzyme A20, an important negative feedback regulator of NF-κB, impairs the expansion of tumor-specific CD8(+) T cells but augments the proliferation of autoimmune CD4(+) T cells. To study the T cell-specific function of A20 in bacterial infection, we infected T cell-specific A20 knockout (CD4-Cre A20(fl/fl)) and control mice with Listeria monocytogenes. A20-deficient pathogen-specific CD8(+) T cells expanded stronger resulting in improved pathogen control at day 7 p.i. Imaging flow cytometry revealed that A20-deficient Listeria-specific CD8(+) T cells underwent increased apoptosis and necroptosis resulting in reduced numbers of memory CD8(+) T cells...
December 22, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27853178/dendritic-cell-elicited-b-cell-activation-fosters-immune-privilege-via-il-10-signals-in-hepatocellular-carcinoma
#17
Fang-Zhu Ouyang, Rui-Qi Wu, Yuan Wei, Rui-Xian Liu, Dong Yang, Xiao Xiao, Limin Zheng, Bo Li, Xiang-Ming Lao, Dong-Ming Kuang
B cells are prominent components of human solid tumours, but activation status and functions of these cells in human cancers remain elusive. Here we establish that over 50% B cells in hepatocellular carcinoma (HCC) exhibit an FcγRII(low/-) activated phenotype, and high infiltration of these cells positively correlates with cancer progression. Environmental semimature dendritic cells, but not macrophages, can operate in a CD95L-dependent pathway to generate FcγRII(low/-) activated B cells. Early activation of monocytes in cancer environments is critical for the generation of semimature dendritic cells and subsequent FcγRII(low/-) activated B cells...
November 17, 2016: Nature Communications
https://www.readbyqxmd.com/read/27763263/endothelial-cell-derived-cd95-ligand-serves-as-a-chemokine-in-induction-of-neutrophil-slow-rolling-and-adhesion
#18
Liang Gao, Gülce Sila Gülcüler, Lieke Golbach, Helena Block, Alexander Zarbock, Ana Martin-Villalba
Integrin activation is crucial for the regulation of leukocyte rolling, adhesion and trans-vessel migration during inflammation and occurs by engagement of myeloid cells through factors presented by inflamed vessels. However, endothelial-dependent mechanisms of myeloid cell recruitment are not fully understood. Here we show using an autoperfused flow chamber assay of whole blood neutrophils and intravital microscopy of the inflamed cremaster muscle that CD95 mediates leukocyte slow rolling, adhesion and transmigration upon binding of CD95-ligand (CD95L) that is presented by endothelial cells...
October 20, 2016: ELife
https://www.readbyqxmd.com/read/27487937/systemic-lupus-erythematosus-new-role-for-cd95l-in-th17-cell-recruitment
#19
Joanna Collison
No abstract text is available yet for this article.
September 2016: Nature Reviews. Rheumatology
https://www.readbyqxmd.com/read/27438772/cd95-mediated-calcium-signaling-promotes-t-helper-17-trafficking-to-inflamed-organs-in-lupus-prone-mice
#20
Amanda Poissonnier, Doriane Sanséau, Matthieu Le Gallo, Marine Malleter, Nicolas Levoin, Roselyne Viel, Lucie Morere, Aubin Penna, Patrick Blanco, Alain Dupuy, Florence Poizeau, Alain Fautrel, Julien Seneschal, Florence Jouan, Jerome Ritz, Edouard Forcade, Nathalie Rioux, Cécile Contin-Bordes, Thomas Ducret, Anne-Marie Vacher, Paul A Barrow, Robin J Flynn, Pierre Vacher, Patrick Legembre
CD95 ligand (CD95L) is expressed by immune cells and triggers apoptotic death. Metalloprotease-cleaved CD95L (cl-CD95L) is released into the bloodstream but does not trigger apoptotic signaling. Hence, the pathophysiological role of cl-CD95L remains unclear. We observed that skin-derived endothelial cells from systemic lupus erythematosus (SLE) patients expressed CD95L and that after cleavage, cl-CD95L promoted T helper 17 (Th17) lymphocyte transmigration across the endothelial barrier at the expense of T regulatory cells...
July 19, 2016: Immunity
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