scholarly journals The Unfolded Protein Response Modulates a Phosphoinositide-Binding Protein through the IRE1-bZIP60 Pathway

2020 ◽  
Vol 183 (1) ◽  
pp. 221-235 ◽  
Author(s):  
Chao-Yuan Yu ◽  
Kazue Kanehara
Keyword(s):  
Unfolded Protein Response ◽  
Binding Protein ◽  
Unfolded Protein ◽  
The Unfolded Protein Response ◽  
Protein Response

scholarly journals Dysregulation in the Unfolded Protein Response in the FGR Rat Pancreas

2020 ◽  
Vol 2020 ◽  
pp. 1-11 ◽  
Author(s):  
Xiaomei Liu ◽  
Yanyan Guo ◽  
Jun Wang ◽  
Liangliang Zhu ◽  
Linlin Gao
Keyword(s):  
Protein Kinase ◽  
Unfolded Protein Response ◽  
Binding Protein ◽  
Protein Kinase R ◽  
Pregnant Rats ◽  
Fetal Pancreas ◽  
Unfolded Protein ◽  
The Unfolded Protein Response ◽  
Protein Response ◽  
Upr Pathway

Accumulating evidence suggests that fetal growth restriction (FGR) leads to the development of diabetes mellitus in adults. The aim of this study was to investigate the effect of protein malnutrition in utero on the pancreatic unfolded protein response (UPR) pathway in FGR offspring. An FGR model was developed by feeding a low-protein diet to pregnant rats throughout gestation. Eighty-four UPR pathway components in the pancreas were investigated by quantitative PCR arrays and confirmed by qPCR and western blotting. Activating transcription factor (Atf4 and Atf6), herpud1, protein kinase R-like endoplasmic reticulum kinase (Perk), X-box binding protein 1 (Xbp1), and the phosphorylation of eIF2α were upregulated, while cyclic AMP-responsive element-binding protein 3-like protein was markedly downregulated in FGR fetuses compared with controls. Investigation in adult offspring revealed temporal changes, for most UPR factors restored to normal, except that dysregulation of Atf6 and Creb3l3 maintained until adulthood. Moreover, autophagy was suppressed in FGR fetal pancreas and may be associated with decreased activation of AMP-activated protein kinase (Ampk). Apoptosis regulators Bax and cleaved-caspase 3 and 9 were upregulated in FGR fetal pancreas. Given that islet size and number were decreased in FGR fetus, we speculated that the aberrant intrauterine milieu impaired UPR signaling in fetal pancreas development. Whether these alterations early in life contribute to the predisposition of FGR fetuses to adult metabolic disorders invites further exploration.

scholarly journals miR‐34c‐5p modulates X‐box–binding protein 1 (XBP1) expression during the adaptive phase of the unfolded protein response

2019 ◽  
Vol 33 (10) ◽  
pp. 11541-11554 ◽  
Author(s):  
Sylwia Bartoszewska ◽  
Aleksandra Cabaj ◽  
Michał Dąbrowski ◽  
James F. Collawn ◽  
Rafal Bartoszewski
Keyword(s):  
Unfolded Protein Response ◽  
Binding Protein ◽  
Unfolded Protein ◽  
The Unfolded Protein Response ◽  
Protein Response

scholarly journals Staufen 1 amplifies pro-apoptotic activation of the unfolded protein response

2019 ◽  
Author(s):  
Mandi Gandelman ◽  
Warunee Dansithong ◽  
Karla P Figueroa ◽  
Sharan Paul ◽  
Daniel R Scoles ◽  
...  
Keyword(s):  
Unfolded Protein Response ◽  
Cortical Neurons ◽  
Rna Binding ◽  
Binding Protein ◽  
Unfolded Protein ◽  
Functional Consequences ◽  
Exogenous Expression ◽  
The Unfolded Protein Response ◽  
Protein Response

AbstractStaufen-1 (STAU1) is an RNA binding protein that becomes highly overabundant in numerous neurodegenerative disease models, including those carrying mutations in presenilin1 (PSEN1), microtubule associated protein tau (MAPT), huntingtin (HTT), TAR DNA-binding protein-43 gene (TARDBP) or C9orf72. We previously reported that elevations in STAU1 determine autophagy defects. Additional functional consequences of STAU1 overabundance, however, have not been investigated. We studied the role of STAU1 in the chronic activation of the Unfolded Protein Response (UPR), a common feature among the neurodegenerative diseases where STAU1 is increased, and is directly associated with neuronal death. Here we report that STAU1 is a novel modulator of the UPR, and is required for apoptosis induced by activation of the PERK-CHOP pathway. STAU1 levels increased in response to multiple ER stressors and exogenous expression of STAU1 was sufficient to cause apoptosis through the PERK-CHOP pathway of the UPR. Cortical neurons and skin fibroblasts derived from Stau1−/− mice showed reduced UPR and apoptosis when challenged with thapsigargin. In fibroblasts from SCA2 patients or with ALS-causing TDP-43 and C9ORF72 mutations we found highly increased STAU1 and CHOP levels in basal conditions. STAU1 knockdown restored CHOP levels to normal. Taken together, these results show STAU1 overabundance reduces cellular resistance to ER stress and precipitates apoptosis.

BCL-2 modulates the unfolded protein response by enhancing splicing of X-box binding protein-1

2015 ◽  
Vol 466 (1) ◽  
pp. 40-45 ◽  
Author(s):  
Triona Ni Chonghaile ◽  
Sanjeev Gupta ◽  
Mohan John ◽  
Eva Szegezdi ◽  
Susan E. Logue ◽  
...  
Keyword(s):  
Unfolded Protein Response ◽  
Binding Protein ◽  
Unfolded Protein ◽  
The Unfolded Protein Response ◽  
Protein Response

scholarly journals Preventing the unfolded protein response via aberrant activation of 4E-binding protein 1 by versipelostatin

2009 ◽  
Vol 100 (2) ◽  
pp. 327-333 ◽  
Author(s):  
Junichi Matsuo ◽  
Yoshinori Tsukumo ◽  
Junko Sakurai ◽  
Satomi Tsukahara ◽  
Hae-Ryong Park ◽  
...  
Keyword(s):  
Unfolded Protein Response ◽  
Binding Protein ◽  
Unfolded Protein ◽  
The Unfolded Protein Response ◽  
Protein Response
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