title: The unfolded protein response and cellular senescence. A review in the theme: cellular mechanisms of endoplasmic reticulum stress signaling in health and disease.
abstract: The endoplasmic reticulum (ER) is a multifunctional organelle critical for the proper folding and assembly of secreted and transmembrane proteins. Perturbations of ER functions cause ER stress, which activates a coordinated system of transcriptional and translational controls called the unfolded protein response (UPR), to cope with accumulation of misfolded proteins and proteotoxicity. It results in ER homeostasis restoration or in cell death. Senescence is a complex cell phenotype induced by several stresses such as telomere attrition, DNA damage, oxidative stress, and activation of some oncogenes. It is mainly characterized by a cell enlargement, a permanent cell-cycle arrest, and the production of a secretome enriched in proinflammatory cytokines and components of the extracellular matrix. Senescent cells accumulate with age in tissues and are suspected to play a role in age-associated diseases. Since senescence is a stress response, the question arises of whether an ER stress could occur concomitantly with senescence and participate in the onset or maintenance of the senescent features. Here, we described the interconnections between the UPR signaling and the different aspects of the cellular senescence programs and discuss the implication of UPR modulations in this context.
authors.affiliation: Centre National de la Recherche Scientifique, UMR8161, Institut de Biologie de Lille, Lille, France; Université Lille 1 Sciences et Techniques, Villeneuve d'Ascq, France; Université Lille 2 Droit et Santé, Lille, France; and Institut Pasteur de Lille, Lille, France olivier.pluquet@ibl.cnrs.fr.
authors.forename: Olivier
authors.initials: O
authors.lastname: Pluquet
authors.affiliation: Centre National de la Recherche Scientifique, UMR8161, Institut de Biologie de Lille, Lille, France; Université Lille 1 Sciences et Techniques, Villeneuve d'Ascq, France; Université Lille 2 Droit et Santé, Lille, France; and Institut Pasteur de Lille, Lille, France.
authors.forename: Albin
authors.initials: A
authors.lastname: Pourtier
authors.affiliation: Centre National de la Recherche Scientifique, UMR8161, Institut de Biologie de Lille, Lille, France; Université Lille 1 Sciences et Techniques, Villeneuve d'Ascq, France; Université Lille 2 Droit et Santé, Lille, France; and Institut Pasteur de Lille, Lille, France.
authors.forename: Corinne
authors.initials: C
authors.lastname: Abbadie
mesh_terms: D000375:Aging / Q000378:metabolism / Q000473:pathology; D000818:Animals; D016922:Cellular Senescence; D004721:Endoplasmic Reticulum / Q000378:metabolism* / Q000473:pathology; D059865:Endoplasmic Reticulum Stress; D006801:Humans; D010641:Phenotype; D015398:Signal Transduction; D056811:Unfolded Protein Response
keywords: ATF6α; IRE1α; PERK; endoplasmic reticulum stress; oxidative stress; senescence; signaling; unfolded protein response