4 results on '"VAFFIDES, Chantal"'
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2. An Evolution-Guided Analysis Reveals a Multi-Signaling Regulation of Fas by Tyrosine Phosphorylation and its Implication in Human Cancers
- Author
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Jérôme Durivault, Angélique Bole, Benoit Dérijard, Eszter Doma, Anne-Odile Hueber, Sébastien Huault, Krittalak Chakrabandhu, Ly Ta Ngoc, Kévin Lang, Michel Pierres, Jean-Pierre Gérard, Institut de Biologie Valrose (IBV), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Radiothérapie [CAL, Nice], Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA)-UNICANCER-Université Côte d'Azur (UCA), This work was supported by institutional funds from the Centre National de la Recherche Scientifique (CNRS) and the Institut National de la Santé et de la Recherche Médicale (INSERM), and by grants from the Institut National du Cancer (INCa, PLBIO09-317), the University of Nice, the Agence Nationale de la Recherche (ANR-10-BLAN-1226, ANR-11-LABX-0028-01). KL was supported by funding from the Canceropole PACA, and LTN was supported by a scholarship from the ministry and education of training of the socialist republic of Vietnam., ANR-10-BLAN-1226,PLAF,Etude du rôle de la plasticité de la signalisation du récepteur Fas dans les adénocarcinomes colo-rectaux.(2010), ANR-11-LABX-0028,SIGNALIFE,Réseau d'Innovation sur les Voies de Signalisation en Sciences de la Vie(2011), Université Nice Sophia Antipolis (... - 2019) (UNS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), VAFFIDES, Chantal, BLANC - Etude du rôle de la plasticité de la signalisation du récepteur Fas dans les adénocarcinomes colo-rectaux. - - PLAF2010 - ANR-10-BLAN-1226 - BLANC - VALID, Centres d'excellences - Réseau d'Innovation sur les Voies de Signalisation en Sciences de la Vie - - SIGNALIFE2011 - ANR-11-LABX-0028 - LABX - VALID, UNICANCER-Université Côte d'Azur (UCA), and HUEBER, Anne-Odile
- Subjects
0301 basic medicine ,Cell viability testing ,[SDV]Life Sciences [q-bio] ,Apoptosis ,Protein tyrosine phosphatase ,Biochemistry ,Fas ligand ,chemistry.chemical_compound ,Aromatic Amino Acids ,0302 clinical medicine ,Cell Signaling ,Neoplasms ,Small interfering RNAs ,Post-Translational Modification ,Amino Acids ,Tyrosine ,Biology (General) ,Phosphorylation ,Animal Signaling and Communication ,Cell Analysis ,ComputingMilieux_MISCELLANEOUS ,Cell Death ,Animal Behavior ,Organic Compounds ,Kinase ,Protein Tyrosine Phosphatase, Non-Receptor Type 6 ,General Neuroscience ,Fas receptor ,Endocytosis ,Signaling Cascades ,3. Good health ,Cell biology ,Nucleic acids ,[SDV] Life Sciences [q-bio] ,Chemistry ,src-Family Kinases ,Bioassays and Physiological Analysis ,Cell Processes ,030220 oncology & carcinogenesis ,Physical Sciences ,Cell lines ,[SDV.IMM]Life Sciences [q-bio]/Immunology ,Biological cultures ,General Agricultural and Biological Sciences ,Research Article ,Signal Transduction ,[SDV.IMM] Life Sciences [q-bio]/Immunology ,QH301-705.5 ,Molecular Sequence Data ,Immunoblotting ,macromolecular substances ,Biology ,General Biochemistry, Genetics and Molecular Biology ,Evolution, Molecular ,03 medical and health sciences ,Apoptotic signaling cascade ,Hydroxyl Amino Acids ,Genetics ,Humans ,Amino Acid Sequence ,fas Receptor ,Non-coding RNA ,Archived Twee ,Behavior ,General Immunology and Microbiology ,Organic Chemistry ,Chemical Compounds ,Biology and Life Sciences ,Proteins ,Tyrosine phosphorylation ,Cell Biology ,Protein Structure, Tertiary ,Gene regulation ,Research and analysis methods ,030104 developmental biology ,SW480 cells ,chemistry ,Mutagenesis, Site-Directed ,RNA ,Gene expression ,Zoology - Abstract
Demonstrations of both pro-apoptotic and pro-survival abilities of Fas (TNFRSF6/CD95/APO-1) have led to a shift from the exclusive “Fas apoptosis” to “Fas multisignals” paradigm and the acceptance that Fas-related therapies face a major challenge, as it remains unclear what determines the mode of Fas signaling. Through protein evolution analysis, which reveals unconventional substitutions of Fas tyrosine during divergent evolution, evolution-guided tyrosine-phosphorylated Fas proxy, and site-specific phosphorylation detection, we show that the Fas signaling outcome is determined by the tyrosine phosphorylation status of its death domain. The phosphorylation dominantly turns off the Fas-mediated apoptotic signal, while turning on the pro-survival signal. We show that while phosphorylations at Y232 and Y291 share some common functions, their contributions to Fas signaling differ at several levels. The findings that Fas tyrosine phosphorylation is regulated by Src family kinases (SFKs) and the phosphatase SHP-1 and that Y291 phosphorylation primes clathrin-dependent Fas endocytosis, which contributes to Fas pro-survival signaling, reveals for the first time the mechanistic link between SFK/SHP-1-dependent Fas tyrosine phosphorylation, internalization route, and signaling choice. We also demonstrate that levels of phosphorylated Y232 and Y291 differ among human cancer types and differentially respond to anticancer therapy, suggesting context-dependent involvement of Fas phosphorylation in cancer. This report provides a new insight into the control of TNF receptor multisignaling by receptor phosphorylation and its implication in cancer biology, which brings us a step closer to overcoming the challenge in handling Fas signaling in treatments of cancer as well as other pathologies such as autoimmune and degenerative diseases., Signalling by the tumor necrosis factor receptor (TNFR) superfamily member Fas can promote either survival or death of a cell, but the mechanism underlying this choice is unclear. This study reveals that the outcome of Fas signalling (death versus survival) is determined by the tyrosine phosphorylation status of its death domain., Author Summary The versatility of the tumor necrosis factor receptor superfamily members in cell fate regulation is well illustrated by the dual signaling generated by one of the most extensively studied members of the family, Fas (CD95/TNFSFR6). Upon binding its ligand, Fas is able to elicit both pro-death and pro-survival signals. Until now, we have lacked mechanistic knowledge about when and how one signaling output of Fas is favored over the other. We demonstrate here that the outcome of Fas signaling is determined by the phosphorylation status of two tyrosine residues (Y232 and Y291) within the death domain. Dephosphorylation of Fas tyrosines by SHP-1 tyrosine phosphatase turns on the pro-apoptotic signal whereas the tyrosine phosphorylation by Src family kinases (SFKs) turns off the pro-apoptotic signal and turns on the pro-survival signal. Furthermore, we provide evidence that Fas tyrosine phosphorylation status may vary among different cancer types and influence the response to anti-cancer treatments. This information reveals an opportunity to use the screening of Fas tyrosine phosphorylation, a newly discovered direct molecular indicator of Fas functional output, to aid the design of Fas-related cancer therapies.
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- 2016
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3. Macrophage origin and self-renewal
- Author
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Sieweke, Michael, VAFFIDES, Chantal, Centre d'Immunologie de Marseille - Luminy (CIML), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), and Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
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[SDV.IMM] Life Sciences [q-bio]/Immunology ,[SDV.IMM]Life Sciences [q-bio]/Immunology ,ComputingMilieux_MISCELLANEOUS - Abstract
International audience; no abstract
- Published
- 2016
4. Natural Killer Cells Preface
- Author
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Eric Vivier, Di Santo, James, Moretta, Alessandro, Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Vivier, E and DiSanto, J and Moretta, VAFFIDES, Chantal, Vivier, E and DiSanto, J and Moretta, A, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)
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[SDV.IMM] Life Sciences [q-bio]/Immunology ,[SDV.IMM]Life Sciences [q-bio]/Immunology ,ComputingMilieux_MISCELLANEOUS - Abstract
International audience; no abstract
- Published
- 2016
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