Journal ArticleDOI
Targeting the unfolded protein response in disease
TLDR
Recent advances in the design of novel compounds and therapeutic strategies to manipulate levels of ER stress in disease are discussed.Abstract:
Stress induced by the accumulation of unfolded proteins in the endoplasmic reticulum (ER) is observed in many diseases, including cancer, diabetes and neurodegenerative disorders. Cellular adaptation to ER stress is achieved by the activation of the unfolded protein response (UPR). Hetz and colleagues discuss the opportunities to modulate components of UPR signalling to therapeutically manipulate levels of ER stress in disease.read more
Citations
More filters
Journal Article
Patterns of Somatic Mutation in Human Cancer Genomes
TL;DR: In this paper, the coding exons of the family of 518 protein kinases were sequenced in 210 cancers of diverse histological types to explore the nature of the information that will be derived from cancer genome sequencing.
Journal ArticleDOI
The Unfolded Protein Response and Cell Fate Control
Claudio Hetz,Feroz R. Papa +1 more
TL;DR: Recent advances into how the UPR integrates information about the intensity and duration of ER stress stimuli in order to control cell fate inform an evolving mechanistic understanding of a wide variety of human diseases, thus opening up the potential for new therapeutic modalities to treat these diverse diseases.
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
Targeting the translation machinery in cancer
Mamatha Bhat,Nathaniel Robichaud,Laura Hulea,Nahum Sonenberg,Jerry Pelletier,Ivan Topisirovic +5 more
TL;DR: The role of translation in cancer is discussed, with a particular focus on the eIF4F (eukaryotic translation initiation factor 4F) complex, and an overview of recent efforts aiming to 'translate' these results to the clinic is provided.
References
More filters
Journal ArticleDOI
An Integrated Genomic Analysis of Human Glioblastoma Multiforme
D. Williams Parsons,Siân Jones,Xiaosong Zhang,Jimmy Lin,Rebecca J. Leary,Philipp Angenendt,Parminder Mankoo,Hannah Carter,I-Mei Siu,Gary L. Gallia,Alessandro Olivi,Roger E. McLendon,B.K. Ahmed Rasheed,Stephen T. Keir,Tatiana Nikolskaya,Yuri Nikolsky,Dana A. Busam,Hanna Tekleab,Luis A. Diaz,James Hartigan,Doug R. Smith,Robert L. Strausberg,Suely Kazue Nagahashi Marie,Sueli Mieko Oba Shinjo,Hai Yan,Gregory J. Riggins,Darell D. Bigner,Rachel Karchin,Nick Papadopoulos,Giovanni Parmigiani,Bert Vogelstein,Victor E. Velculescu,Kenneth W. Kinzler +32 more
TL;DR: Recurrent mutations in the active site of isocitrate dehydrogenase 1 (IDH1) occurred in a large fraction of young patients and in most patients with secondary GBMs and were associated with an increase in overall survival.
Journal ArticleDOI
The Unfolded Protein Response: From Stress Pathway to Homeostatic Regulation
Peter Walter,David Ron +1 more
TL;DR: The vast majority of proteins that a cell secretes or displays on its surface first enter the endoplasmic reticulum, where they fold and assemble, and only properly assembled proteins advance from the ER to the cell surface.
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.
Journal ArticleDOI
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
Regulated Translation Initiation Controls Stress-Induced Gene Expression in Mammalian Cells
Heather P. Harding,Isabel Novoa,Yuhong Zhang,Huiqing Zeng,Ronald C. Wek,Matthieu Schapira,David Ron +6 more
TL;DR: Protein kinases that phosphorylate the alpha subunit of eukaryotic initiation factor 2 (eIF2alpha) are activated in stressed cells and negatively regulate protein synthesis, resulting in the induction of the downstream gene CHOP (GADD153).
Related Papers (5)
The Unfolded Protein Response: From Stress Pathway to Homeostatic Regulation
Peter Walter,David Ron +1 more
Signal integration in the endoplasmic reticulum unfolded protein response
David Ron,Peter Walter +1 more