unfolded protein response

Summary

Summary: A cellular response to environmental insults that cause disruptions in PROTEIN FOLDING and/or accumulation of defectively folded protein in the ENDOPLASMIC RETICULUM. It consists of a group of regulatory cascades that are triggered as a response to altered levels of calcium and/or the redox state of the endoplasmic reticulum. Persistent activation of the unfolded protein response leads to the induction of APOPTOSIS.

Top Publications

  1. Morita S, Villalta S, Feldman H, Register A, Rosenthal W, Hoffmann Petersen I, et al. Targeting ABL-IRE1α Signaling Spares ER-Stressed Pancreatic β Cells to Reverse Autoimmune Diabetes. Cell Metab. 2017;25:883-897.e8 pubmed publisher
    ..Our data support a model wherein ER-stressed β cells contribute to their own demise during T1D pathogenesis and implicate the ABL-IRE1α axis as a drug target for the treatment of an autoimmune disease. ..
  2. Brozzi F, Gerlo S, Grieco F, Nardelli T, Lievens S, Gysemans C, et al. A combined "omics" approach identifies N-Myc interactor as a novel cytokine-induced regulator of IRE1 protein and c-Jun N-terminal kinase in pancreatic beta cells. J Biol Chem. 2014;289:20677-93 pubmed
    ..These cytokines induce endoplasmic reticulum stress and the unfolded protein response (UPR), contributing to the loss of beta cells...
  3. Hamdan N, Kritsiligkou P, Grant C. ER stress causes widespread protein aggregation and prion formation. J Cell Biol. 2017;216:2295-2304 pubmed publisher
    ..This activates the unfolded protein response (UPR), which alters the expression of many genes involved in ER quality control...
  4. Moulis J, Thevenod F. New perspectives in cadmium toxicity: an introduction. Biometals. 2010;23:763-8 pubmed publisher
  5. Bao Q, Zhao M, Chen L, Wang Y, Wu S, Wu W, et al. MicroRNA-297 promotes cardiomyocyte hypertrophy via targeting sigma-1 receptor. Life Sci. 2017;175:1-10 pubmed publisher
    ..Additionally, the function of miR-297 in cardiomyocyte hypertrophy and ER stress/unfolded protein response (UPR) signaling pathway was investigated by transfecting miR-297 mimics/inhibitor...
  6. Mitsuhashi Y, Furusawa Y, Aradate T, Zhao Q, Moniruzzaman R, Kanamori M, et al. 3-O-trans-p-coumaroyl-alphitolic acid, a triterpenoid from Zizyphus jujuba, leads to apoptotic cell death in human leukemia cells through reactive oxygen species production and activation of the unfolded protein response. PLoS ONE. 2017;12:e0183712 pubmed publisher
    ..RNA-seq analysis revealed that the expression of transcripts associated with the unfolded protein response (UPR), such as spliced XBP-1 and CHOP, were up-regulated by 3OTPCA treatment...
  7. Brown M, Strus E, Naidoo N. Reduced Sleep During Social Isolation Leads to Cellular Stress and Induction of the Unfolded Protein Response. Sleep. 2017;40: pubmed publisher
    ..We previously demonstrated that acute sleep loss in flies and mice induced the unfolded protein response (UPR), an adaptive signaling pathway...
  8. Guo Q, Jin S, Hu H, Zhou Y, Yan Y, Zong H, et al. Hypoxia in 3T3-L1 adipocytes suppresses adiponectin expression via the PERK and IRE1 unfolded protein response. Biochem Biophys Res Commun. 2017;493:346-351 pubmed publisher
    ..The purpose of this study was to investigate the specific role of the unfolded protein response (UPR) involved in the low expression of adiponectin induced by hypoxia...
  9. Murao N, Nishitoh H. Role of the unfolded protein response in the development of central nervous system. J Biochem. 2017;162:155-162 pubmed publisher
    The unfolded protein response (UPR) is an intracellular homeostatic signalling pathway that is induced by accumulated misfolded/unfolded proteins in the endoplasmic reticulum (ER)...

More Information

Publications84

  1. Piret S, Olinger E, Reed A, Nesbit M, Hough T, Bentley L, et al. A mouse model for inherited renal fibrosis associated with endoplasmic reticulum stress. Dis Model Mech. 2017;10:773-786 pubmed publisher
    ..mutant mice, and this was accompanied, both in vivo and ex vivo, by upregulation of two unfolded protein response pathways in primary thick ascending limb cells from homozygous mutant mice...
  2. Kenny T, Hart P, Ragazzi M, Sersinghe M, Chipuk J, Sagar M, et al. Selected mitochondrial DNA landscapes activate the SIRT3 axis of the UPRmt to promote metastasis. Oncogene. 2017;36:4393-4404 pubmed publisher
    ..of all metastatic cells are characterized by activation of the SIRT/FOXO/SOD2 axis of the mitochondrial unfolded protein response (UPRmt)...
  3. Llamas E, Pulido P, Rodríguez Concepción M. Interference with plastome gene expression and Clp protease activity in Arabidopsis triggers a chloroplast unfolded protein response to restore protein homeostasis. PLoS Genet. 2017;13:e1007022 pubmed publisher
    ..This sort of chloroplast unfolded protein response (cpUPR) mechanism appears to be mediated by the heat shock transcription factor HsfA2...
  4. Ishikawa T, Toyama T, Nakamura Y, Tamada K, Shimizu H, Ninagawa S, et al. UPR transducer BBF2H7 allows export of type II collagen in a cargo- and developmental stage-specific manner. J Cell Biol. 2017;216:1761-1774 pubmed publisher
    The unfolded protein response (UPR) handles unfolded/misfolded proteins accumulated in the endoplasmic reticulum (ER). However, it is unclear how vertebrates correctly use the total of ten UPR transducers...
  5. Shah P, Dupre T, Siskind L, Beverly L. Common cytotoxic chemotherapeutics induce epithelial-mesenchymal transition (EMT) downstream of ER stress. Oncotarget. 2017;8:22625-22639 pubmed publisher
    ..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...
  6. Hong F, Liu B, Wu B, Morreall J, Roth B, Davies C, et al. CNPY2 is a key initiator of the PERK-CHOP pathway of the unfolded protein response. Nat Struct Mol Biol. 2017;24:834-839 pubmed publisher
    The unfolded protein response (UPR) in the endoplasmic reticulum (ER) is a highly conserved protein-quality-control mechanism critical for cells to make survival-or-death decisions under ER-stress conditions...
  7. Vincenz Donnelly L, Hipp M. The endoplasmic reticulum: A hub of protein quality control in health and disease. Free Radic Biol Med. 2017;108:383-393 pubmed publisher
    ..Here, we describe the components of the ERQC machinery, investigate their response to different forms of stress, and discuss the consequences of ERQC break-down. ..
  8. Shah D, Singh S, Dzieciatkowska M, Mallela K. Biophysical analysis of the effect of chemical modification by 4-oxononenal on the structure, stability, and function of binding immunoglobulin protein (BiP). PLoS ONE. 2017;12:e0183975 pubmed publisher
    ..It also plays a key role in the unfolded protein response (UPR) in the endoplasmic reticulum...
  9. Martinez G, Hetz C. Cell-nonautonomous control of the UPR. EMBO Rep. 2012;13:767-8 pubmed publisher
  10. Hou W, Gupta S, Beauchamp M, Yuan L, Jerome Majewska L. Non-alcoholic fatty liver disease in mice with heterozygous mutation in TMED2. PLoS ONE. 2017;12:e0182995 pubmed publisher
    ..Deletion or mutations of Tmed genes in yeast and Drosophila results in ER-stress and activation of the unfolded protein response (UPR)...
  11. Ojha R, Amaravadi R. Targeting the unfolded protein response in cancer. Pharmacol Res. 2017;120:258-266 pubmed publisher
    ..To cope with these situations, cancer cells evoke a highly conserved adaptive mechanism called the unfolded protein response (UPR) to restore the ER homeostasis...
  12. Qureshi M, Haynes C, Pellegrino M. The mitochondrial unfolded protein response: Signaling from the powerhouse. J Biol Chem. 2017;292:13500-13506 pubmed publisher
    ..and restore homeostasis, including the activation of retrograde pathways such as the mitochondrial unfolded protein response (UPRmt)...
  13. Martinez G, Duran Aniotz C, Cabral Miranda F, Vivar J, Hetz C. Endoplasmic reticulum proteostasis impairment in aging. Aging Cell. 2017;16:615-623 pubmed publisher
    ..In fact, ER stress is a common feature of most neurodegenerative diseases. The unfolded protein response (UPR) operates as central player to maintain ER homeostasis or the induction of cell death of ..
  14. Bhoola N, Kramvis A. Expression of wild-type or G1862T mutant HBe antigen of subgenotype A1 of hepatitis B virus and the unfolded protein response in Huh7 cells. J Gen Virol. 2017;98:1422-1433 pubmed publisher
    ..Secretion of HBsAg and HBeAg, preC/C/HBeAg expression in the secretory pathway, activation of the unfolded protein response (UPR) and subsequent activation of apoptosis were monitored...
  15. Smith M, Wilkinson S. ER homeostasis and autophagy. Essays Biochem. 2017;61:625-635 pubmed publisher
    ..The most studied signalling mechanism that the ER employs is the unfolded protein response (UPR), which is known to increase a number of effector mechanisms, including autophagy...
  16. Onn A, Ron D. Modeling the endoplasmic reticulum unfolded protein response. Nat Struct Mol Biol. 2010;17:924-5 pubmed publisher
    ..A detailed quantitative model of signaling by IRE1 sheds light on the mechanism of its activation by endoplasmic reticulum stress and addresses a long-standing controversy in the field. ..
  17. Gregersen N, Bross P. Protein misfolding and cellular stress: an overview. Methods Mol Biol. 2010;648:3-23 pubmed publisher
    ..e., mitophagy or mitoptosis, and related to the generation and cellular effects of oxidatively modified proteins, which closes a vicious cycle of protein misfolding and oxidative stress. ..
  18. Alhusban A, Kozak A, Pillai B, Ahmed H, Sayed M, Johnson M, et al. Mechanisms of acute neurovascular protection with AT1 blockade after stroke: Effect of prestroke hypertension. PLoS ONE. 2017;12:e0178867 pubmed publisher
    ..Candesartan induced prorecovery signaling was mediated through eNOS. This effect was not maintained at 7 days after experimental ischemia. ..
  19. Lin S, Taatjes D. ?Np53 and aging. Aging (Albany NY). 2013;5:717-8 pubmed
  20. Frakes A, Dillin A. The UPRER: Sensor and Coordinator of Organismal Homeostasis. Mol Cell. 2017;66:761-771 pubmed publisher
    ..to proteotoxic perturbations, cells have evolved compartment-specific stress responses, such as the unfolded protein response of the endoplasmic reticulum (UPRER)...
  21. Zhang X, Cook K, Warri A, Cruz I, Rosim M, Riskin J, et al. Lifetime Genistein Intake Increases the Response of Mammary Tumors to Tamoxifen in Rats. Clin Cancer Res. 2017;23:814-824 pubmed publisher
    ..We observed downregulation of unfolded protein response (UPR) and autophagy-related genes (GRP78, IRE1α, ATF4, and Beclin-1) and genes linked to ..
  22. Wu H, Ng B, Thibault G. Endoplasmic reticulum stress response in yeast and humans. Biosci Rep. 2014;34: pubmed publisher
    ..One of the best-characterized pathways, the UPR (unfolded protein response), is an intracellular signal transduction pathway that monitors ER (endoplasmic reticulum) homoeostasis...
  23. Workman P, Davies F. A stressful life (or death): combinatorial proteotoxic approaches to cancer-selective therapeutic vulnerability. Oncotarget. 2011;2:277-80 pubmed
  24. Stan R, Silva R, de Camargo M. Human GRP78 affinity towards its signaling partners Ire1? and PERK is differently modulated by an unfolded protein client. Biochem Biophys Res Commun. 2017;487:375-380 pubmed publisher
    ..The unfolded protein response (UPR) thus triggered is a proteostatic signaling network that adapts the protein-folding capacity of the ..
  25. Lewy T, Grabowski J, Bloom M. BiP: Master Regulator of the Unfolded Protein Response and Crucial Factor in Flavivirus Biology?. Yale J Biol Med. 2017;90:291-300 pubmed
    ..Flaviviruses can interact with several ER processes, including the unfolded protein response (UPR), a cellular stress mechanism responsible for managing unfolded protein accumulation and ER stress...
  26. Stoveken B. Tau pathology as a cause and consequence of the UPR. J Neurosci. 2013;33:14285-7 pubmed publisher
  27. Huang P, Jheng J, Arnold J, Wang J, Cameron C, Shih S. UGGT1 enhances enterovirus 71 pathogenicity by promoting viral RNA synthesis and viral replication. PLoS Pathog. 2017;13:e1006375 pubmed publisher
    Positive-strand RNA virus infections can induce the stress-related unfolded protein response (UPR) in host cells...
  28. Okumura N, Kitahara M, Okuda H, Hashimoto K, Ueda E, Nakahara M, et al. Sustained Activation of the Unfolded Protein Response Induces Cell Death in Fuchs' Endothelial Corneal Dystrophy. Invest Ophthalmol Vis Sci. 2017;58:3697-3707 pubmed publisher
    The unfolded protein response (UPR) is believed to play a role in the pathogenesis of Fuchs' endothelial corneal dystrophy (FECD)...
  29. Tavernier S, Osorio F, Vandersarren L, Vetters J, Vanlangenakker N, Van Isterdael G, et al. Regulated IRE1-dependent mRNA decay sets the threshold for dendritic cell survival. Nat Cell Biol. 2017;19:698-710 pubmed publisher
    ..Furthermore, loss of IRE1 endonuclease on top of XBP1 led to cDC1 loss in the intestine. Thus, mucosal DCs differentially mount ATF4- and IRE1-dependent adaptive mechanisms to survive in the face of ER stress. ..
  30. Fang L, Gong J, Wang Y, Liu R, Li Z, Wang Z, et al. MICA/B expression is inhibited by unfolded protein response and associated with poor prognosis in human hepatocellular carcinoma. J Exp Clin Cancer Res. 2014;33:76 pubmed publisher
    ..The unfolded protein response is one of the main causes of resistance to chemotherapy and radiotherapy in tumor cells...
  31. Briggs J, Ren L, Chakrabarti K, Tsai Y, Weissman A, Hansen R, et al. Activation of the unfolded protein response in sarcoma cells treated with rapamycin or temsirolimus. PLoS ONE. 2017;12:e0185089 pubmed publisher
    Activation of the unfolded protein response (UPR) in eukaryotic cells represents an evolutionarily conserved response to physiological stress...
  32. Li L, Sawashita J, Ding X, Yang M, Xu Z, Miyahara H, et al. Caloric restriction reduces the systemic progression of mouse AApoAII amyloidosis. PLoS ONE. 2017;12:e0172402 pubmed publisher
    ..analyses of the liver suggested that CR treatment might improve the symptoms of inflammation, the unfolded protein response induced by amyloid deposits and oxidative stress...
  33. Pellegrino M, Haynes C. Mitophagy and the mitochondrial unfolded protein response in neurodegeneration and bacterial infection. BMC Biol. 2015;13:22 pubmed publisher
    ..Here, we explore the roles of mitochondrial autophagy (mitophagy) and the mitochondrial unfolded protein response (UPR(mt)) in the response to mitochondrial dysfunction, focusing in particular on recent evidence on the ..
  34. Amin Wetzel N, Saunders R, Kamphuis M, Rato C, Preissler S, Harding H, et al. A J-Protein Co-chaperone Recruits BiP to Monomerize IRE1 and Repress the Unfolded Protein Response. Cell. 2017;171:1625-1637.e13 pubmed publisher
    When unfolded proteins accumulate in the endoplasmic reticulum (ER), the unfolded protein response (UPR) increases ER-protein-folding capacity to restore protein-folding homeostasis...
  35. Jiang M, Yu S, Yu Z, Sheng H, Li Y, Liu S, et al. XBP1 (X-Box-Binding Protein-1)-Dependent O-GlcNAcylation Is Neuroprotective in Ischemic Stroke in Young Mice and Its Impairment in Aged Mice Is Rescued by Thiamet-G. Stroke. 2017;48:1646-1654 pubmed publisher
    ..To restore endoplasmic reticulum function impaired by stress, the unfolded protein response is activated...
  36. Latorre Pellicer A, Moreno Loshuertos R, Lechuga Vieco A, Sanchez Cabo F, Torroja C, Acin Perez R, et al. Mitochondrial and nuclear DNA matching shapes metabolism and healthy ageing. Nature. 2016;535:561-5 pubmed
  37. Zhang D, Tong X, VanDommelen K, Gupta N, Stamper K, Brady G, et al. Lipogenic transcription factor ChREBP mediates fructose-induced metabolic adaptations to prevent hepatotoxicity. J Clin Invest. 2017;127:2855-2867 pubmed publisher
    ..levels of molecular chaperones and activated the C/EBP homologous protein-dependent (CHOP-dependent) unfolded protein response, whereas administration of a chemical chaperone or Chop shRNA rescued liver injury...
  38. Ponsero A, Igbaria A, Darch M, Miled S, Outten C, Winther J, et al. Endoplasmic Reticulum Transport of Glutathione by Sec61 Is Regulated by Ero1 and Bip. Mol Cell. 2017;67:962-973.e5 pubmed publisher
    ..Thus, the ER redox poise is tuned by reciprocal control of glutathione import and Ero1 activation. The ER protein-conducting channel is permeable to small molecules, provided the driving force of a concentration gradient. ..
  39. Mollereau B. Establishing links between endoplasmic reticulum-mediated hormesis and cancer. Mol Cell Biol. 2013;33:2372-4 pubmed publisher
  40. Mohler K, Mann R, Bullwinkle T, Hopkins K, Hwang L, Reynolds N, et al. Editing of misaminoacylated tRNA controls the sensitivity of amino acid stress responses in Saccharomyces cerevisiae. Nucleic Acids Res. 2017;45:3985-3996 pubmed publisher
    ..These findings show that during amino acid starvation a primary role of aaRS quality control is to help the cell mount an effective stress response, independent of the role of editing in maintaining translational accuracy. ..
  41. Ren Z, Chen S, Qing T, Xuan J, Couch L, Yu D, et al. Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017;392:11-21 pubmed publisher
    ..We found that leflunomide caused endoplasmic reticulum (ER) stress and activated an unfolded protein response, as evidenced by increased expression of related genes including CHOP and GADD34; and elevated protein ..
  42. Shah D, Romero F, Guo Z, Sun J, Li J, Kallen C, et al. Obesity-Induced Endoplasmic Reticulum Stress Causes Lung Endothelial Dysfunction and Promotes Acute Lung Injury. Am J Respir Cell Mol Biol. 2017;57:204-215 pubmed publisher
    ..Our work suggests that reducing protein load in the ER of pulmonary endothelial cells might protect against acute respiratory distress syndrome in obese individuals. ..
  43. Kim E, Sakata K, Liao F. Bidirectional interplay of HSF1 degradation and UPR activation promotes tau hyperphosphorylation. PLoS Genet. 2017;13:e1006849 pubmed publisher
    The unfolded protein response (UPR) in the endoplasmic reticulum (ER) and the cytoplasmic heat stress response are two major stress response systems necessary for maintaining proteostasis for cellular health...
  44. Halbleib K, Pesek K, Covino R, Hofbauer H, Wunnicke D, Hänelt I, et al. Activation of the Unfolded Protein Response by Lipid Bilayer Stress. Mol Cell. 2017;67:673-684.e8 pubmed publisher
    The unfolded protein response (UPR) is a conserved homeostatic program that is activated by misfolded proteins in the lumen of the endoplasmic reticulum (ER)...
  45. Liu Y, Chen Y, Zhang J, Liu Y, Zhang Y, Su Z. Retinoic acid receptor-related orphan receptor ? stimulates adipose tissue inflammation by modulating endoplasmic reticulum stress. J Biol Chem. 2017;292:13959-13969 pubmed publisher
    ..The relationships established here between ROR? expression, inflammation, and UPR signaling may have implications for therapeutic targeting of obesity-related metabolic diseases. ..
  46. Taguchi Y, Horiuchi Y, Kano F, Murata M. Novel prosurvival function of Yip1A in human cervical cancer cells: constitutive activation of the IRE1 and PERK pathways of the unfolded protein response. Cell Death Dis. 2017;8:e2718 pubmed publisher
    ..To survive, they constitutively activate the unfolded protein response (UPR)...
  47. Chan S, Zhao X, Elfowiris A, Ratnam C, Herbert T. The role of de novo protein synthesis and SIRT1 in ER stress-induced Atf4 and Chop mRNA expression in mammalian cells. Biochimie. 2017;138:156-167 pubmed publisher
    Endoplasmic reticulum (ER) stress and the activation of the unfolded protein response (UPR) have been implicated in the pathogenesis of many common human diseases...
  48. Namba T. Regulation of endoplasmic reticulum functions. Aging (Albany NY). 2015;7:901-2 pubmed
  49. Nicolao M, Loos J, Rodríguez Rodrígues C, Beas V, Cumino A. Bortezomib initiates endoplasmic reticulum stress, elicits autophagy and death in Echinococcus granulosus larval stage. PLoS ONE. 2017;12:e0181528 pubmed publisher
  50. Merksamer P, Papa F. The UPR and cell fate at a glance. J Cell Sci. 2010;123:1003-6 pubmed publisher
  51. Cubillos Ruiz J, Bettigole S, Glimcher L. Tumorigenic and Immunosuppressive Effects of Endoplasmic Reticulum Stress in Cancer. Cell. 2017;168:692-706 pubmed publisher
  52. Mohamed E, Cao Y, Rodriguez P. Endoplasmic reticulum stress regulates tumor growth and anti-tumor immunity: a promising opportunity for cancer immunotherapy. Cancer Immunol Immunother. 2017;66:1069-1078 pubmed publisher
    ..We postulate that the inhibition of ER stress or the UPR-related elements could represent a significant approach to increase the efficacy of various forms of cancer immunotherapy. ..
  53. Byun S, Namba T, Lee S. Losing p53 loosens up ER-stress. Aging (Albany NY). 2015;7:895-6 pubmed
  54. Grechowa I, Horke S, Wallrath A, Vahl C, Dorweiler B. Human neutrophil elastase induces endothelial cell apoptosis by activating the PERK-CHOP branch of the unfolded protein response. FASEB J. 2017;31:3868-3881 pubmed publisher
    ..Apoptosis was assayed by capsase-3/7 activation, TUNEL, and sub-G1 assay. Activation of unfolded protein response (UPR) effector molecules binding Ig protein, soluble X-binding protein-1, protein kinase RNA-like ER ..
  55. Freis P, Bollard J, Lebeau J, Massoma P, Fauvre J, Vercherat C, et al. mTOR inhibitors activate PERK signaling and favor viability of gastrointestinal neuroendocrine cell lines. Oncotarget. 2017;8:20974-20987 pubmed publisher
    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...
  56. Bhardwaj R, Bhardwaj A, Tandon C, Dhawan D, Bijarnia R, Kaur T. Implication of hyperoxaluria on osteopontin and ER stress mediated apoptosis in renal tissue of rats. Exp Mol Pathol. 2017;102:384-390 pubmed publisher
    ..was analysed for crystal depositions, osteopontin expression, inflammation, ER stress and subsequent unfolded protein response intermediates (UPR)...
  57. Halliday M, Radford H, Zents K, Molloy C, Moreno J, Verity N, et al. Repurposed drugs targeting eIF2α-P-mediated translational repression prevent neurodegeneration in mice. Brain. 2017;140:1768-1783 pubmed publisher
    ..Signalling through the PERK/eIF2α-P branch of the unfolded protein response plays a critical role in controlling protein synthesis rates in cells...
  58. Schaeffer C, Merella S, Pasqualetto E, Lazarevic D, Rampoldi L. Mutant uromodulin expression leads to altered homeostasis of the endoplasmic reticulum and activates the unfolded protein response. PLoS ONE. 2017;12:e0175970 pubmed publisher
    ..Interestingly, mutant uromodulin expression induces the Unfolded Protein Response (UPR), and specifically the IRE1 branch, as shown by an increased splicing of XBP1...
  59. Balasubramanyam M, Singh L, Rangasamy S. Molecular intricacies and the role of ER stress in diabetes. Exp Diabetes Res. 2012;2012:958169 pubmed publisher
  60. Bohnert K, McMillan J, Kumar A. Emerging roles of ER stress and unfolded protein response pathways in skeletal muscle health and disease. J Cell Physiol. 2018;233:67-78 pubmed publisher
    ..To alleviate the stress and restore homeostasis, the ER activates a signaling network called the unfolded protein response (UPR)...
  61. Olou A, Sarkar A, Bele A, Gurumurthy C, Mir R, Ammons S, et al. Mammalian ECD Protein Is a Novel Negative Regulator of the PERK Arm of the Unfolded Protein Response. Mol Cell Biol. 2017;37: pubmed publisher
    ..Taken together, our data demonstrate that ECD promotes survival upon ER stress by increasing GRP78 protein levels to enhance the adaptive folding protein in the ER to attenuate PERK signaling. ..
  62. Rojas Benítez D, Eggers C, Glavic A. Modulation of the Proteostasis Machinery to  Overcome Stress Caused by Diminished Levels of  t6A-Modified tRNAs in Drosophila. Biomolecules. 2017;7: pubmed publisher
    ..knockdown genes required for t6A synthesis in a tissue and time specific manner and in vivo reporters of unfolded protein response (UPR) activation...
  63. Cybulsky A. Endoplasmic reticulum stress, the unfolded protein response and autophagy in kidney diseases. Nat Rev Nephrol. 2017;13:681-696 pubmed publisher
    ..in our understanding of the mechanisms of endoplasmic reticulum (ER) proteostasis, ER stress and the unfolded protein response (UPR), as well as ER stress-induced autophagy, in the kidney...
  64. Grant S. Enhancing proteotoxic stress as an anticancer strategy. Oncotarget. 2011;2:284-6 pubmed
  65. Nagelkerke A, Bussink J, Mujcic H, Wouters B, Lehmann S, Sweep F, et al. Hypoxia stimulates migration of breast cancer cells via the PERK/ATF4/LAMP3-arm of the unfolded protein response. Breast Cancer Res. 2013;15:R2 pubmed publisher
    ..Furthermore, hypoxic tumors are associated with a poor prognosis. Besides the HIF-1 pathway, the unfolded protein response (UPR) is also induced by hypoxic conditions...
  66. Cameron N. Role of endoplasmic reticulum stress in diabetic neuropathy. Diabetes. 2013;62:696-7 pubmed publisher
  67. Zaglia T, Milan G, Ruhs A, Franzoso M, Bertaggia E, Pianca N, et al. Atrogin-1 deficiency promotes cardiomyopathy and premature death via impaired autophagy. J Clin Invest. 2014;124:2410-24 pubmed publisher
    ..to degrade CHMP2B, resulting in autophagy impairment, intracellular protein aggregate accumulation, unfolded protein response activation, and subsequent cardiomyocyte apoptosis, all of which increased progressively with age...
  68. Sobue S, Inoue C, Hori F, Qiao S, Murate T, Ichihara M. Molecular hydrogen modulates gene expression via histone modification and induces the mitochondrial unfolded protein response. Biochem Biophys Res Commun. 2017;493:318-324 pubmed publisher
    ..we showed that H2 simultaneously induced the H3K27 demethylase, Jmjd3, and mitochondrial unfolded protein response (mtUPR)-related genes...
  69. Darling N, Balmanno K, Cook S. ERK1/2 signalling protects against apoptosis following endoplasmic reticulum stress but cannot provide long-term protection against BAX/BAK-independent cell death. PLoS ONE. 2017;12:e0184907 pubmed publisher
    Disruption of protein folding in the endoplasmic reticulum (ER) causes ER stress. Activation of the unfolded protein response (UPR) acts to restore protein homeostasis or, if ER stress is severe or persistent, drive apoptosis, which is ..
  70. Ahmadi A, Khansarinejad B, Hosseinkhani S, Ghanei M, Mowla S. miR-199a-5p and miR-495 target GRP78 within UPR pathway of lung cancer. Gene. 2017;620:15-22 pubmed publisher
    ..One of the signal transduction pathways related to NSCLC is Unfolded Protein Response (UPR), which is mainly regulated by GRP78 (HSPA5, Gene ID: 3309)...
  71. Duan H, Li Y, Arora D, Xu D, Lim H, Wang W. Discovery of a Benzamide Derivative That Protects Pancreatic ?-Cells against Endoplasmic Reticulum Stress. J Med Chem. 2017;60:6191-6204 pubmed publisher
    ..alleviates ER stress in ?-cells by suppressing ER stress-mediated activation of all three branches of unfolded protein response (UPR) and apoptotic genes...
  72. Pinkaew D, Chattopadhyay A, King M, Chunhacha P, Liu Z, Stevenson H, et al. Fortilin binds IRE1? and prevents ER stress from signaling apoptotic cell death. Nat Commun. 2017;8:18 pubmed publisher
    ..Endoplasmic reticulum stress causes unfolded proteins to populate the organelle, eliciting the unfolded protein response. During the unfolded protein response, GRP78-an endoplasmic reticulum master stress regulator-detaches ..
  73. Zhang C, Tang Y, Li Y, Xie L, Zhuang W, Liu J, et al. Unfolded protein response plays a critical role in heart damage after myocardial ischemia/reperfusion in rats. PLoS ONE. 2017;12:e0179042 pubmed publisher
    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...
  74. Roy G, Zhang S, Li L, Higham E, Wu H, Marelli M, et al. Development of a fluorescent reporter system for monitoring ER stress in Chinese hamster ovary cells and its application for therapeutic protein production. PLoS ONE. 2017;12:e0183694 pubmed publisher
    ..of mis- and unfolded protein in the endoplasmic reticulum (ER) causes ER stress and initiates the unfolded protein response (UPR) that results in an activation of protein folding machinery, translation attenuation in an effort ..
  75. Madhusudhan T, Wang H, Ghosh S, Dong W, Kumar V, Al Dabet M, et al. Signal integration at the PI3K-p85-XBP1 hub endows coagulation protease activated protein C with insulin-like function. Blood. 2017;130:1445-1455 pubmed publisher
    ..mapping of condition-specific XBP1-transcriptional regulatory patterns confirmed that concordant unfolded protein response target genes are involved in maintenance of ER proteostasis by both insulin and aPC...