IRE1α Induces Thioredoxin-Interacting Protein to Activate the NLRP3 Inflammasome and Promote Programmed Cell Death under Irremediable ER Stress
Alana G. Lerner,John-Paul Upton,P. V.K. Praveen,Rajarshi Ghosh,Yoshimi Nakagawa,Aeid Igbaria,Sarah Shen,Vinh Son Nguyen,Bradley J. Backes,Myriam Heiman,Myriam Heiman,Myriam Heiman,Nathaniel Heintz,Paul Greengard,Simon T. Hui,Qizhi Tang,Ala Trusina,Scott A. Oakes,Feroz R. Papa +18 more
TLDR
The IRE1α-TXNIP pathway is used in the terminal UPR to promote sterile inflammation and programmed cell death and may be targeted to develop effective treatments for cell degenerative diseases.About:
This article is published in Cell Metabolism.The article was published on 2012-08-08 and is currently open access. It has received 679 citations till now. The article focuses on the topics: TXNIP & Thioredoxin-Interacting Protein.read more
Citations
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Journal ArticleDOI
ER stress-induced cell death mechanisms
Renata Sano,John C. Reed +1 more
TL;DR: Recent advances in understanding the diversity of molecular mechanisms that govern ER stress signaling in health and disease are summarized.
Journal ArticleDOI
Protein misfolding in the endoplasmic reticulum as a conduit to human disease
Miao Wang,Randal J. Kaufman +1 more
TL;DR: In eukaryotic cells, the endoplasmic reticulum is essential for the folding and trafficking of proteins that enter the secretory pathway and contributes to the aetiology of many human diseases.
Journal ArticleDOI
Reactive Oxygen Species in Metabolic and Inflammatory Signaling.
TL;DR: The role of ROS in the regulation metabolic/inflammatory diseases including atherosclerosis, diabetes mellitus, and stroke is highlighted and the balance ROS signaling plays in both physiology and pathophysiology is understood.
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
Endoplasmic Reticulum Stress and Oxidative Stress in Cell Fate Decision and Human Disease
TL;DR: A greater fundamental understanding of the mechanisms that preserve protein folding homeostasis and redox status will provide new information toward the development of novel therapeutics for many human diseases.
References
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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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Protein translation and folding are coupled by an endoplasmic-reticulum-resident kinase
TL;DR: The cloning of perk is described, a gene encoding a type I transmembrane ER-resident protein that contains a protein-kinase domain most similar to that of the known eIF2α kinases, PKR and HRI that implicate PERK in a signalling pathway that attenuates protein translation in response to ER stress.
Journal ArticleDOI
Regulation of mRNA Translation and Stability by microRNAs
TL;DR: In this article, the authors describe principles of miRNA-mRNA interactions and proteins that interact with miRNAs and function in miRNA mediated repression, and discuss the multiple, often contradictory, mechanisms that miRNA have been reported to use, which cause translational repression and mRNA decay.
Journal ArticleDOI
IRE1 couples endoplasmic reticulum load to secretory capacity by processing the XBP-1 mRNA
Marcella Calfon,Huiqing Zeng,Fumihiko Urano,Jeffery H. Till,Stevan R. Hubbard,Heather P. Harding,Scott G. Clark,David Ron +7 more
TL;DR: It is demonstrated that mutations in either ire-1 or the transcription-factor-encoding xbp-1 gene abolished the UPR in Caenorhabditis elegans, suggesting that physiological ER load regulates a developmental decision in higher eukaryotes.
Journal ArticleDOI
Thioredoxin-interacting protein links oxidative stress to inflammasome activation
TL;DR: The participation of TXNIP in the NLRP3 inflammasome activation may provide a mechanistic link to the observed involvement of IL-1β in the pathogenesis of type 2 diabetes.
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