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UPR IRE1

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https://www.readbyqxmd.com/read/28622297/p53-mediated-suppression-of-bip-triggers-bik-induced-apoptosis-during-prolonged-endoplasmic-reticulum-stress
#1
Ignacio López, Anne-Sophie Tournillon, Rodrigo Prado Martins, Konstantinos Karakostis, Laurence Malbert-Colas, Karin Nylander, Robin Fåhraeus
Physiological and pathological conditions that affect the folding capacity of the endoplasmic reticulum (ER) provoke ER stress and trigger the unfolded protein response (UPR). The UPR aims to either restore the balance between newly synthesized and misfolded proteins or if the damage is severe, to trigger cell death. However, the molecular events underlying the switch between repair and cell death are not well understood. The ER-resident chaperone BiP governs the UPR by sensing misfolded proteins and thereby releasing and activating the three mediators of the UPR: PERK, IRE1 and ATF6...
June 16, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28615521/ier3ip1-deficiency-leads-to-increased-%C3%AE-cell-death-and-decreased-%C3%AE-cell-proliferation
#2
Juan Sun, Decheng Ren
Mutations in the gene for Immediate Early Response 3 Interacting Protein 1 (IER3IP1) cause permanent neonatal diabetes mellitus in human. The mechanisms involved have not been determined and the role of IER3IP1 in β-cell survival has not been characterized. In order to determine if there is a molecular link between IER3IP1 deficiency and β-cell survival and proliferation, we knocked down Ier3ip1 gene expression in mouse MIN6 insulinoma cells. IER3IP1 suppression induced apoptotic cell death which was associated with an increase in Bim and a decrease in Bcl-xL...
May 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28591178/unfolded-protein-response-plays-a-critical-role-in-heart-damage-after-myocardial-ischemia-reperfusion-in-rats
#3
Chengcheng Zhang, Yi Tang, Yanming Li, Liang Xie, Wei Zhuang, Jing Liu, Jianbin Gong
The unfolded protein response (UPR) plays a critical role in cell death mediated by ischemia/reperfusion (I/R) injury. However, little is known about the exact mechanism of UPR signaling pathways after myocardial I/R injury in rats. An attempt was therefore made to assess whether the myocardial I/R induced UPR, and which branch of UPR (ATF6, IRE1 and PERK) signal pathway was activated. Sprague-Dawley rats were pretreated with UPR stimulator dithiothreitol (DTT) and UPR inhibitor 4-phenylbutyrate (4PBA) and then subjected to myocardial I/R surgery...
2017: PloS One
https://www.readbyqxmd.com/read/28588081/intercellular-transmission-of-the-unfolded-protein-response-promotes-survival-and-drug-resistance-in-cancer-cells
#4
Jeffrey J Rodvold, Kevin T Chiu, Nobuhiko Hiramatsu, Julia K Nussbacher, Valentina Galimberti, Navin R Mahadevan, Karl Willert, Jonathan H Lin, Maurizio Zanetti
Increased protein translation in cells and various factors in the tumor microenvironment can induce endoplasmic reticulum (ER) stress, which initiates the unfolded protein response (UPR). We have previously reported that factors released from cancer cells mounting a UPR induce a de novo UPR in bone marrow-derived myeloid cells, macrophages, and dendritic cells that facilitates protumorigenic characteristics in culture and tumor growth in vivo. We investigated whether this intercellular signaling, which we have termed transmissible ER stress (TERS), also operates between cancer cells and what its functional consequences were within the tumor...
June 6, 2017: Science Signaling
https://www.readbyqxmd.com/read/28559891/systematic-optimization-of-protein-secretory-pathways-in-saccharomyces-cerevisiae-to-increase-expression-of-hepatitis-b-small-antigen
#5
Jiayuan Sheng, Hunter Flick, Xueyang Feng
Hepatitis B is a major disease that chronically infects millions of people in the world, especially in developing countries. Currently, one of the effective vaccines to prevent Hepatitis B is the Hepatitis B Small Antigen (HBsAg), which is mainly produced by the recombinant yeast Saccharomyces cerevisiae. In order to bring down the price, which is still too high for people in developing countries to afford, it is important to understand key cellular processes that limit protein expression. In this study, we took advantage of yeast knockout collection (YKO) and screened 194 S...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28467788/sphingosine-kinase-2-inhibition-synergises-with-bortezomib-to-target-myeloma-by-enhancing-endoplasmic-reticulum-stress
#6
Craig T Wallington-Beddoe, Melissa K Bennett, Kate Vandyke, Lorena Davies, Julia R Zebol, Paul A B Moretti, Melissa R Pitman, Duncan R Hewett, Andrew C W Zannettino, Stuart M Pitson
The proteasome inhibitor bortezomib has proven to be invaluable in the treatment of myeloma. By exploiting the inherent high immunoglobulin protein production of malignant plasma cells, bortezomib induces endoplasmic reticulum (ER) stress and the unfolded protein response (UPR), resulting in myeloma cell death. In most cases, however, the disease remains incurable highlighting the need for new therapeutic targets. Sphingosine kinase 2 (SK2) has been proposed as one such therapeutic target for myeloma. Our observations that bortezomib and SK2 inhibitors independently elicited induction of ER stress and the UPR prompted us to examine potential synergy between these agents in myeloma...
April 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28437467/mutant-uromodulin-expression-leads-to-altered-homeostasis-of-the-endoplasmic-reticulum-and-activates-the-unfolded-protein-response
#7
Céline Schaeffer, Stefania Merella, Elena Pasqualetto, Dejan Lazarevic, Luca Rampoldi
Uromodulin is the most abundant urinary protein in physiological conditions. It is exclusively produced by renal epithelial cells lining the thick ascending limb of Henle's loop (TAL) and it plays key roles in kidney function and disease. Mutations in UMOD, the gene encoding uromodulin, cause autosomal dominant tubulointerstitial kidney disease uromodulin-related (ADTKD-UMOD), characterised by hyperuricemia, gout and progressive loss of renal function. While the primary effect of UMOD mutations, retention in the endoplasmic reticulum (ER), is well established, its downstream effects are still largely unknown...
2017: PloS One
https://www.readbyqxmd.com/read/28423496/mtor-inhibitors-activate-perk-signaling-and-favor-viability-of-gastrointestinal-neuroendocrine-cell-lines
#8
Patricia Freis, Julien Bollard, Justine Lebeau, Patrick Massoma, Joëlle Fauvre, Cécile Vercherat, Thomas Walter, Serge Manié, Colette Roche, Jean-Yves Scoazec, Carole Ferraro-Peyret
mTOR and Unfolded Protein Response (UPR) are two signaling pathways frequently activated in cancer cells. The mTOR pathway has been shown to be up-regulated in most gastroenteropancreatic neuroendocrine tumors. In contrast, little is known about the UPR status in neoplastic neuroendocrine cells. However, these hormone-producing cells are likely to present distinctive adaptations of this pathway, as other secretory cells. We therefore analyzed the status of the three axes of UPR and their relation to mTOR pathway in two gastrointestinal neuroendocrine tumors (GI-NET) cell lines STC-1 and GluTag...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28403212/longitudinal-monitoring-of-gaussia-and-nano-luciferase-activities-to-concurrently-assess-er-calcium-homeostasis-and-er-stress-in-vivo
#9
Emily S Wires, Mark J Henderson, Xiaokang Yan, Susanne Bäck, Kathleen A Trychta, Molly H Lutrey, Brandon K Harvey
The endoplasmic reticulum (ER) is essential to many cellular processes including protein processing, lipid metabolism and calcium storage. The ability to longitudinally monitor ER homeostasis in the same organism would offer insight into progressive molecular and cellular adaptations to physiologic or pathologic states, but has been challenging. We recently described the creation of a Gaussia luciferase (GLuc)-based secreted ER calcium-modulated protein (SERCaMP or GLuc-SERCaMP) to longitudinally monitor ER calcium homeostasis...
2017: PloS One
https://www.readbyqxmd.com/read/28364133/in-brachypodium-a-complex-signaling-is-actuated-to-protect-cells-from-proteotoxic-stress-and-facilitate-seed-filling
#10
Sang-Jin Kim, Starla Zemelis-Durfee, Curtis Wilkerson, Federica Brandizzi
A conserved UPR machinery is required for Brachypodium ER stress resistance and grain filling. Human and livestock diets depend on the accumulation of cereal storage proteins and carbohydrates, including mixed-linkage glucan (MLG), in the endosperm during seed development. Storage proteins and proteins responsible for the production of carbohydrates are synthesized in the endoplasmic reticulum (ER). Unfavorable conditions during growth that hamper the ER biosynthetic capacity, such as heat, can cause a potentially lethal condition known as ER stress, which activates the unfolded protein response (UPR), a signaling response designed to mitigate ER stress...
July 2017: Planta
https://www.readbyqxmd.com/read/28358375/novel-prosurvival-function-of-yip1a-in-human-cervical-cancer-cells-constitutive-activation-of-the-ire1-and-perk-pathways-of-the-unfolded-protein-response
#11
Yuki Taguchi, Yuta Horiuchi, Fumi Kano, Masayuki Murata
Cancer cells are under chronic endoplasmic reticulum (ER) stress due to hypoxia, low levels of nutrients, and a high metabolic demand for proliferation. To survive, they constitutively activate the unfolded protein response (UPR). The inositol-requiring protein 1 (IRE1) and protein kinase RNA-like ER kinase (PERK) signaling branches of the UPR have been shown to have cytoprotective roles in cancer cells. UPR-induced autophagy is another prosurvival strategy of cancer cells, possibly to remove misfolded proteins and supply nutrients...
March 30, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28341998/ire1-signaling-exacerbates-alzheimer-s-disease-pathogenesis
#12
Claudia Duran-Aniotz, Victor Hugo Cornejo, Sandra Espinoza, Álvaro O Ardiles, Danilo B Medinas, Claudia Salazar, Andrew Foley, Ivana Gajardo, Peter Thielen, Takao Iwawaki, Wiep Scheper, Claudio Soto, Adrian G Palacios, Jeroen J M Hoozemans, Claudio Hetz
Altered proteostasis is a salient feature of Alzheimer's disease (AD), highlighting the occurrence of endoplasmic reticulum (ER) stress and abnormal protein aggregation. ER stress triggers the activation of the unfolded protein response (UPR), a signaling pathway that enforces adaptive programs to sustain proteostasis or eliminate terminally damaged cells. IRE1 is an ER-located kinase and endoribonuclease that operates as a major stress transducer, mediating both adaptive and proapoptotic programs under ER stress...
March 24, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28332979/the-perk-arm-of-the-unfolded-protein-response-regulates-satellite-cell-mediated-skeletal-muscle-regeneration
#13
Guangyan Xiong, Sajedah M Hindi, Aman K Mann, Yann S Gallot, Kyle R Bohnert, Douglas R Cavener, Scott R Whittemore, Ashok Kumar
Regeneration of skeletal muscle in adults is mediated by satellite stem cells. Accumulation of misfolded proteins triggers endoplasmic reticulum stress that leads to unfolded protein response (UPR). The UPR is relayed to the cell through the activation of PERK, IRE1/XBP1, and ATF6. Here, we demonstrate that levels of PERK and IRE1 are increased in satellite cells upon muscle injury. Inhibition of PERK, but not the IRE1 arm of the UPR in satellite cells inhibits myofiber regeneration in adult mice. PERK is essential for the survival and differentiation of activated satellite cells into the myogenic lineage...
March 23, 2017: ELife
https://www.readbyqxmd.com/read/28270144/prototype-foamy-virus-elicits-complete-autophagy-involving-the-er-stress-related-upr-pathway
#14
Peipei Yuan, Lanlan Dong, Qingqing Cheng, Shuang Wang, Zhi Li, Yan Sun, Song Han, Jun Yin, Biwen Peng, Xiaohua He, Wanhong Liu
BACKGROUND: Prototype foamy virus (PFV) is a member of the Spumaretrovirinae subfamily of retroviruses, which maintains lifelong latent infection while being nonpathogenic to their natural hosts. Autophagy is a cell-programmed mechanism that plays a pivotal role in controlling homeostasis and defense against exotic pathogens. However, whether autophagy is the mechanism for host defense in PFV infection has not been investigated. FINDINGS: Our results revealed that PFV infection induced the accumulation of autophagosomes and triggered complete autophagic flux in BHK-21 cells...
March 7, 2017: Retrovirology
https://www.readbyqxmd.com/read/28266275/molecular-basis-of-human-diseases-and-targeted-therapy-based-on-small-molecule-inhibitors-of-er-stress-induced-signaling-pathways
#15
W Rozpędek, A Nowak, D Pytel, J Alan Diehl, I Majsterek
The Endoplasmic Reticulum (ER) provides a conserved protein quality control system and plays a fundamental role in cell growth and homeostasis. Disturbances in the ER homeostasis may originate especially from hypoxia, glucose deficiency, presence of mutant proteins, that directly impair protein folding capacity and after deposition of unfolded and misfolded proteins within ER lumen trigger ER stress conditions. That subsequently activates the Unfolded Protein Response (UPR) branches, which has a dual pro-adaptive or pro-apoptotic role dependently on severity and time of duration of ER stress conditions...
March 6, 2017: Current Molecular Medicine
https://www.readbyqxmd.com/read/28192116/prrt2-inhibits-the-proliferation-of-glioma-cells-by-modulating-unfolded-protein-response-pathway
#16
Guanghui Bi, Jingfeng Yan, Shuzhen Sun, Xinhua Qu
Accumulating studies reported mutations in the gene encoding the proline-rich transmembrane protein 2 (PRRT2) to be causative for several paroxysmal neurological disorders, including paroxysmal kinesigenic dyskinesia (PKD), PKD combined with infantile seizures (ICCA), and benign familial infantile seizures (BFIS). However, the impact of PRRT2 in tumorigenesis is not known. Based on a large-scale data analysis, we found that PRRT2 was down-regulated in glioma tumor tissues compared with normal brain tissue. Dysregulation of PRRT2 was not induced by mutation, copy number variation and epigenetic modification, but modulated by microRNA-30a-5p...
April 1, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28186986/common-cytotoxic-chemotherapeutics-induce-epithelial-mesenchymal-transition-emt-downstream-of-er-stress
#17
Parag P Shah, Tess V Dupre, Leah J Siskind, Levi J Beverly
Endoplasmic reticulum (ER) in eukaryotes is a main organelle involved in a wide variety of functions including calcium storage, lipid biosynthesis, protein folding and protein transport. Disruption of ER homeostasis leads to ER stress and activation of the unfolded protein response (UPR). We and others have previously found that ER stress induces EMT in different cellular systems. Induction of ER stress with chemical modulators of ER homeostasis was sufficient to activate an EMT-like state in all cellular systems tested...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28155228/athop3-a-member-of-the-hop-family-in-arabidopsis-interacts-with-bip-and-plays-a-major-role-in-the-er-stress-response
#18
Nuria Fernández-Bautista, Lourdes Fernández-Calvino, Alfonso Muñoz, M Mar Castellano
HOP is a well-studied family of cytosolic cochaperones. However, the possible role of HOP during the ER stress response and their interactors within the ER were not previously addressed in any eukaryote. We have demonstrated that Arabidopsis HOP3, whose function was not studied before, interacts in vivo with cytosolic HSP90 and HSP70, and, unexpectedly, with BiP, a HSP70 ER-resident protein. Although BiP lacks the domain described in other eukaryotes for HOP-HSP70 binding, it interacts with HOP3 through a noncanonical association to its nucleotide binding domain...
February 2, 2017: Plant, Cell & Environment
https://www.readbyqxmd.com/read/28137856/targeting-ire1-with-small-molecules-counteracts-progression-of-atherosclerosis
#19
Ozlem Tufanli, Pelin Telkoparan Akillilar, Diego Acosta-Alvear, Begum Kocaturk, Umut Inci Onat, Syed Muhammad Hamid, Ismail Çimen, Peter Walter, Christian Weber, Ebru Erbay
Metaflammation, an atypical, metabolically induced, chronic low-grade inflammation, plays an important role in the development of obesity, diabetes, and atherosclerosis. An important primer for metaflammation is the persistent metabolic overloading of the endoplasmic reticulum (ER), leading to its functional impairment. Activation of the unfolded protein response (UPR), a homeostatic regulatory network that responds to ER stress, is a hallmark of all stages of atherosclerotic plaque formation. The most conserved ER-resident UPR regulator, the kinase/endoribonuclease inositol-requiring enzyme 1 (IRE1), is activated in lipid-laden macrophages that infiltrate the atherosclerotic lesions...
February 21, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28105371/unfolding-anti-tumor-immunity-er-stress-responses-sculpt-tolerogenic-myeloid-cells-in-cancer
#20
REVIEW
Juan R Cubillos-Ruiz, Eslam Mohamed, Paulo C Rodriguez
Established tumors build a stressful and hostile microenvironment that blocks the development of protective innate and adaptive immune responses. Different subsets of immunoregulatory myeloid populations, including dendritic cells, myeloid-derived suppressor cells (MDSCs) and macrophages, accumulate in the stressed tumor milieu and represent a major impediment to the success of various forms of cancer immunotherapy. Specific conditions and factors within tumor masses, including hypoxia, nutrient starvation, low pH, and increased levels of free radicals, provoke a state of "endoplasmic reticulum (ER) stress" in both malignant cells and infiltrating myeloid cells...
2017: Journal for Immunotherapy of Cancer
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