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THESE DE DOCTORAT DE L'UNIVERSITE DE RENNES 1 COMUE UNIVERSITE BRETAGNE LOIRE ECOLE DOCTORALE N° 605 Biologie Santé Spécialité : Cancerology Par Dimitrios Doultsinos Targeting IRE1 activity in Glioblastoma Multiforme Thèse présentée et soutenue à Rennes, le 05.04.2019 Unité de recherche : INSERM U1242 Rapporteurs avant soutenance : Fabienne Foufelle DR1, INSERM UMRS1138, Paris, France. Stephane Rocchi DR2, INSERM U1065, Nice, France. Composition du Jury : Président : Nicolas Pallet Professor, Hôpital Européen Georges-Pompidou, Paris, France. Examinateurs : Sophie Janssens Professor, VIB-UGent Center for Inflammation Research, Gent, Belgium. Nicolas Pallet Professor, Hôpital Européen Georges-Pompidou, Paris, France. Dir. de thèse : Dr Eric Chevet DR1, INSERM U1242, Rennes, France. Invité(s) Leif A. Eriksson Professor, Department of chemistry and molecular biology, University of Göteborg, Göteborg, Sweden. Targeting IRE1 activity in Glioblastoma Multiforme D. Doultsinos For my mum and dad. You have shown me hard work and perseverance like no one ever will. You have always supported me through an absurd rollercoaster of a life so far whether I deserved it or not. This would not have been possible without you. Summary The endoplasmic reticulum (ER) is a membranous intracellular organelle and the first compartment of the secretory pathway. As such, the ER contributes to the production and folding of approximately one-third of cellular proteins, and is thus linked to the maintenance of cellular homeostasis and the fine balance between health and disease. The unfolded protein response (UPR) is an integrated, adaptive biochemical process that controls cell homeostasis and maintains normal physiological function. Accumulation of improperly folded proteins in the ER leads to stress, which may push the UPR past beneficial functions such as reduced protein production and increased folding and clearance, to apoptotic signalling.
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