Induction of apoptosis and activation of NF-κB by CD95 require different signalling thresholds
Patrick Legembre,Bryan C. Barnhart,Lixin Zheng,Shrijay Vijayan,Sharon E. Straus,Jennifer M. Puck,Janet K. Dale,Michael J. Lenardo,Marcus E. Peter +8 more
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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.read more
Citations
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Journal ArticleDOI
S-nitrosylation of the death receptor fas promotes fas ligand-mediated apoptosis in cancer cells.
Lissbeth Leon-Bollotte,Lissbeth Leon-Bollotte,Lissbeth Leon-Bollotte,Selvakumar Subramaniam,Selvakumar Subramaniam,Selvakumar Subramaniam,Olivier Cauvard,Olivier Cauvard,Olivier Cauvard,Stéphanie Plenchette–Colas,Stéphanie Plenchette–Colas,Stéphanie Plenchette–Colas,Catherine Paul,Catherine Paul,Catherine Paul,Cindy Godard,Cindy Godard,Cindy Godard,Antonio Martinez–Ruiz,Patrick Legembre,Jean-François Jeannin,Jean-François Jeannin,Jean-François Jeannin,Ali Bettaieb,Ali Bettaieb,Ali Bettaieb +25 more
TL;DR: Post-translational modifications (S-nitrosylation of cysteine residues 199 and 304) in the cytoplasmic domain of Fas promote redistribution of Fas to lipid rafts, formation of the death-inducing signal complex, and induction of cell death.
Journal ArticleDOI
The naturally processed CD95L elicits a c-yes/calcium/PI3K-driven cell migration pathway.
Sébastien Tauzin,Benjamin Chaigne-Delalande,Benjamin Chaigne-Delalande,Eric Selva,Nadine Khadra,Sophie Daburon,Sophie Daburon,Cécile Contin-Bordes,Patrick Blanco,Jacques Le Seyec,Thomas Ducret,Thomas Ducret,Laurent Counillon,Jean-François Moreau,Paul Hofman,Pierre Vacher,Pierre Vacher,Patrick Legembre +17 more
TL;DR: The role of the metalloprotease-cleaved CD95L is revisited and it is emphasized that the increase in cl-CD95L observed in patients affected by chronic inflammatory disorders may fuel the local or systemic tissue damage by promoting tissue-filtration of immune cells.
Book ChapterDOI
Death Receptor Signaling and Its Function in the Immune System
TL;DR: This chapter discusses the role of death receptor-mediated AICD in regulation of the adaptive immune response against foreign and self antigens in comparison to cytokine deprivation-mediated death by neglect and the contribution of dysregulated death receptor/ligand systems to autoimmune diseases.
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Multidrug resistance in chronic myeloid leukaemia: how much can we learn from MDR-CML cell lines?
TL;DR: The role played by the influx transporter OCT1 (organic cation transporter 1), by efflux ABC transporters, molecules involved in the modulation of apoptosis and other features described in leukaemic cells of clinical samples and CML cell lines are reviewed.
Journal ArticleDOI
CD95-Mediated Calcium Signaling Promotes T Helper 17 Trafficking to Inflamed Organs in Lupus-Prone Mice
Amanda Poissonnier,Amanda Poissonnier,Doriane Sanséau,Doriane Sanséau,Matthieu Le Gallo,Matthieu Le Gallo,Marine Malleter,Nicolas Levoin,Roselyne Viel,Lucie Morere,Lucie Morere,Aubin Penna,Aubin Penna,Patrick Blanco,Patrick Blanco,Alain Dupuy,Florence Poizeau,Alain Fautrel,Julien Seneschal,Julien Seneschal,Florence Jouan,Florence Jouan,Jerome Ritz,Edouard Forcade,Edouard Forcade,Edouard Forcade,Nathalie Rioux,Nathalie Rioux,Cécile Contin-Bordes,Cécile Contin-Bordes,Thomas Ducret,Thomas Ducret,Anne-Marie Vacher,Anne-Marie Vacher,Paul A. Barrow,Robin J. Flynn,Pierre Vacher,Pierre Vacher,Patrick Legembre +38 more
TL;DR: neutralizing the CD95 non-apoptotic signaling pathway could be an attractive therapeutic approach for SLE treatment by generating a cell-penetrating CID peptide that prevented Th17 cell transmigration and alleviated clinical symptoms in lupus mice.
References
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Journal ArticleDOI
Dominant interfering Fas gene mutations impair apoptosis in a human autoimmune lymphoproliferative syndrome
Galen H. Fisher,Fredric J Rosenberg,Sharon E. Straus,Janet K. Dale,Lindsay A. Middelton,Albert Y. Lin,Warren Strober,Michael J. Lenardo,Jennifer M. Puck +8 more
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
P. Lane,M. Lohoff,F. Rieux-Laucat,F. LeDeist,C. Hivroz,A. G. Roberts,K. M. Debatin,A. Fischer +7 more
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
Frédéric Rieux-Laucat,F. Le Deist,C Hivroz,Irene Roberts,Klaus-Michael Debatin,Alain Fischer,J P de Villartay +6 more
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
Marcus E. Peter,Peter H. Krammer +1 more
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
Richard M. Siegel,John K. Frederiksen,David A. Zacharias,Francis Ka-Ming Chan,Michele M. Johnson,David A. Lynch,Roger Y. Tsien,Michael J. Lenardo +7 more
TL;DR: Results show that formation of preassociated receptor complexes is necessary for Fas signaling and dominant interference in human disease.