Journal ArticleDOI
The Unfolded Protein Response: Integrating Stress Signals Through the Stress Sensor IRE1α
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TLDR
An overview of the signaling and regulatory mechanisms underlying IRE1α function is provided and the emerging role of the UPR in adaptation to protein folding stress in specialized secretory cells and in pathological conditions associated with alterations in ER homeostasis is discussed.Abstract:
Stress induced by accumulation of unfolded proteins at the endoplasmic reticulum (ER) is a classic feature of secretory cells and is observed in many tissues in human diseases including cancer, diabetes, obesity, and neurodegeneration. Cellular adaptation to ER stress is achieved by the activation of the unfolded protein response (UPR), an integrated signal transduction pathway that transmits information about the protein folding status at the ER to the nucleus and cytosol to restore ER homeostasis. Inositol-requiring transmembrane kinase/endonuclease-1 (IRE1α), the most conserved UPR stress sensor, functions as an endoribonuclease that processes the mRNA of the transcription factor X-box binding protein-1 (XBP1). IRE1α signaling is a highly regulated process, controlled by the formation of a dynamic scaffold onto which many regulatory components assemble, here referred to as the UPRosome. Here we provide an overview of the signaling and regulatory mechanisms underlying IRE1α function and discuss the emerging role of the UPR in adaptation to protein folding stress in specialized secretory cells and in pathological conditions associated with alterations in ER homeostasis.read more
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The unfolded protein response: controlling cell fate decisions under ER stress and beyond
TL;DR: Insight is provided into the regulatory mechanisms and signalling crosstalk of the three branches of the UPR, which are initiated by the stress sensors protein kinase RNA-like ER kinase (PERK), inositol-requiring protein 1α (IRE1α) and activating transcription factor 6 (ATF6).
Journal ArticleDOI
Cancer cell–autonomous contribution of type I interferon signaling to the efficacy of chemotherapy
Antonella Sistigu,Takahiro Yamazaki,Erika Vacchelli,Kariman Chaba,David Enot,Julien Adam,Ilio Vitale,Aicha Goubar,Elisa E. Baracco,Catarina Remédios,Laetitia Fend,Dalil Hannani,Laetitia Aymeric,Yuting Ma,Mireia Niso-Santano,Oliver Kepp,Joachim L. Schultze,Thomas Tüting,Filippo Belardelli,Laura Bracci,Valentina La Sorsa,Giovanna Ziccheddu,Paola Sestili,Francesca Urbani,Mauro Delorenzi,Magali Lacroix-Triki,Virginie Quidville,Rosa Conforti,Jean Philippe Spano,Lajos Pusztai,Vichnou Poirier-Colame,Suzette Delaloge,Frédérique Penault-Llorca,Sylvain Ladoire,Laurent Arnould,Joanna Cyrta,Marie Charlotte Dessoliers,Alexander M.M. Eggermont,Marco Bianchi,Mikael J. Pittet,Camilla Engblom,Christina Pfirschke,Xavier Préville,Gilles Uzé,Robert D. Schreiber,Melvyn T. Chow,Mark J. Smyth,Enrico Proietti,Fabrice Andre,Guido Kroemer,Laurence Zitvogel +50 more
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Journal ArticleDOI
Consensus guidelines for the detection of immunogenic cell death
Oliver Kepp,Laura Senovilla,Ilio Vitale,Erika Vacchelli,Sandy Adjemian,Patrizia Agostinis,Lionel Apetoh,Fernando Aranda,Vincenzo Barnaba,Norma Bloy,Laura Bracci,Karine Breckpot,David Brough,Aitziber Buqué,Maria G. Castro,Mara Cirone,María Isabel Colombo,Isabelle Cremer,Sandra Demaria,Luciana Dini,Aristides G. Eliopoulos,Alberto Faggioni,Silvia C. Formenti,Jitka Fucikova,Lucia Gabriele,Udo S. Gaipl,Jérôme Galon,Abhishek D. Garg,François Ghiringhelli,Nathalia A. Giese,Zong Sheng Guo,Akseli Hemminki,Martin Herrmann,James W. Hodge,Stefan Holdenrieder,Jamie Honeychurch,Hong-Min Hu,Xing Huang,Timothy M Illidge,Koji Kono,Mladen Korbelik,Dmitri V. Krysko,Sherene Loi,Pedro R. Lowenstein,Enrico Lugli,Yuting Ma,Frank Madeo,Angelo A. Manfredi,Isabelle Martins,Domenico Mavilio,Laurie Menger,Nicolò Merendino,Michael Michaud,Grégoire Mignot,Karen L. Mossman,Gabriele Multhoff,Rudolf Oehler,Fabio Palombo,Theocharis Panaretakis,Jonathan Pol,Enrico Proietti,Jean-Ehrland Ricci,Chiara Riganti,Patrizia Rovere-Querini,Anna Rubartelli,Antonella Sistigu,Mark J. Smyth,Juergen Sonnemann,Radek Spisek,John Stagg,Abdul Qader Sukkurwala,Eric Tartour,Andrew Thorburn,Stephen H. Thorne,Peter Vandenabeele,Francesca Velotti,Samuel T Workenhe,Haining Yang,Wei-Xing Zong,Laurence Zitvogel,Guido Kroemer,Lorenzo Galluzzi +81 more
TL;DR: Strategies conceived to detect surrogate markers of ICD in vitro and to screen large chemical libraries for putative I CD inducers are outlined, based on a high-content, high-throughput platform that was recently developed.
Journal ArticleDOI
Disturbance of endoplasmic reticulum proteostasis in neurodegenerative diseases
Claudio Hetz,Bertrand Mollereau +1 more
TL;DR: An overview of the most recent findings addressing the biological relevance of ER stress in the nervous system is provided.
Journal ArticleDOI
Proteostasis control by the unfolded protein response.
TL;DR: An overview of recent insights into the mechanisms that cells employ to maintain proteostasis and how the unfolded protein response determines cell fate under endoplasmic reticulum stress is provided.
References
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Signal integration in the endoplasmic reticulum unfolded protein response
David Ron,Peter Walter +1 more
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Journal ArticleDOI
XBP1 mRNA Is Induced by ATF6 and Spliced by IRE1 in Response to ER Stress to Produce a Highly Active Transcription Factor
TL;DR: The transcription factor XBP1, a target of ATF6, is identified as a mammalian substrate of such an unconventional mRNA splicing system and it is shown that only the spliced form of X BP1 can activate the UPR efficiently.
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