Global ETD Search
Search theses and dissertations gathered from participating repositories worldwide. Every result links back to the library that holds it. No account is needed.
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Showing 1 to 18 of 18 for “"XBP1"”.
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Establishing The Role Of The Pancreatic Transcription Factor Mist1 In Xbp1-Mediated Maintenance Of Pancreatic Acinar Cell Homeostasis
… us to investigate whether loss of the IRE1/XBP1 branch via conditional ablation of XBP1 in mature mouse PACs could be compensated for by the remaining UPR pathways. We show that survival and homeostasis of PACs is wholly dependent on the IRE1/XBP1 axis of the UPR. Specifically, ablation of …
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X-Box Binding Protein-1 is Important in Maintenance of Endothelial Integrity and Migration
… activation of spliced x-box binding protein-1 (XBP1), an endoplasmic reticulum stress response transcription factor, results in the development of atherosclerosis in apoE -/- mice. Histone deacetylases (HDACs) play a crucial role in transcriptional regulation through modulation of chromatin …
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Structure, Mechanism and Chemical Modulation of the Protein Kinase-nuclease Dual-enzyme IRE1
… a UPR-dedicated transcription factor called XBP1 in metazoans (or HAC1 in yeast) to bolster the productive capacity of the ER and purge misfolded proteins from the ER. To activate XBP1/HAC1, IRE1 cleaves XBP1/HAC1 mRNA twice to eliminate an inhibitory intron using a dormant nuclease function …
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Translational Control by the Ribosome-Associated Complex in the Unfolded Protein Response
… of the IRE1 branch of UPR. When RAC is reduced, Xbp1 mRNA splicing is inhibited upon ER stress. Consistent with this activity, ER stress induces changes in the subcellular distribution of RAC, which coincides with the localization of Xbp1 mRNA. Mechanistically, reduction of RAC affects the …
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The unfolded protein response and HLA-B27 misfolding: implications for ankylosing spondylitis
… by upregulation of BiP and splicing of XBP1, a key step in the IRE1 pathway of the UPR which is increasingly being linked with intestinal inflammation. We also demonstrate that different cell lines respond to different ER stress stimuli in distinct ways. We establish that HT1080 cells …
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Super Low Dose Endotoxin Exacerbates Low Grade Inflammation through Modulating Cell Stress and Decreasing Cellular Homeostatic Protein Expression
… through inducing homeostatic molecules such as XBP1 and GRP78/BiP. We observed that cells challenged with SLD endotoxin have significantly reduced expression of homeostatic molecules XBP1 and BiP. Mechanistically, we observed that SLD-LPS increases phosphorylated HCK expression in TM treated …
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Identification of a Novel Regulator of ER Stress-Induced Apoptosis
… UPR is the Ire1-mediated splicing of unspliced xbp1 (xbp1U) into the potent transcription factor spliced Xbp1 (Xbp1S). If the ER cannot return to homeostasis, the apoptotic program is activated. Programmed cell death (apoptosis) is an evolutionarily conserved, genetically controlled program …
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Ire1 regulates cyp11a1 transcription to mediate steroidogenesis in the ovary
… MKC-4485 and MKC-3946 potently inhibited XBP1 splicing but had no effect CYP11A1 up-regulation in response to forskolin stimulation. Additionally, we sought to determine if XBP1u expression is necessary for up-regulating CYP11A1 in response to forskolin. Using RNA interference, XBP1 …
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The intrinsic role of SOCS1 in intestinal epithelial cells
… autophagy (P62), ER stress response (spliced Xbp1) and apoptosis (cleaved caspase 3 protein), as well as EdU incorporation proliferation assays were then performed. Our results indicate that the loss of Ifng and Socs1 is not affecting colonoid growth and renewal capacity of stem cells, goblet …
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The Unfolded Protein Response Increases Production of Pro-Angiogenic Factors by Tumor Cell Lines
… By chromatin IP experiments, we found that XBP1 bound to the promoter region of VEGF gene in response to ER stress in C6 cells which suggested that XBP1 may transactivate VEGF gene during UPR activation. After testing several stress inducible kinases which have been shown to contribute to …
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Characterization of Palmitic Acid Induced Lipotoxicity in Schwann Cells
… of ER stress signature genes such as CHOP, Xbp1 and GRP78. In SC cultured in euglycemic conditions, lysosomal membrane destabilization preceded mitochondrial membrane depolarization, oxidative stress and caspase 3/7 activation. The release of cathepsin L and B were also observed with PA …
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Altered Responses to Endoplasmic Reticulum Stress In Pancreatic Cancer
… the UPR were assessed: eIF2α/ATF4/CHOP and IRE1α/XBP1s. Pancreatic cancer cells exhibited altered UPR activation characterized by a delay in both phosphorylation of eIF2α and induction of spliced XBP1. Further evaluation of the UPR-mediated effects on cell cycle progression revealed that …
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Gene Delivery of Adenoviral-TMBIM6 Vector Protects the Neonatal Brain after Hypoxic-Ischemic Injury
… was associated with a decrease in IRE1α- XBP1 levels while decreased levels of P4502E1 coupled with upregulation of Nrf-2 and HO-1, anti-oxidant enzymes, were correlated with a reduction in ROS generation and inflammation. In conclusion we established that overexpression of BI-1 attenuated …
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Probing the protein homeostasis mechanisms in long-lived naked mole-rats
… In Chapter 3, RNA-based methods, including an Xbp1 splicing assay and quantitative PCR (RT-qPCR) assays were successfully established to probe the activation and outputs of the UPR in a NMR kidney fibroblast cell line in response to tunicamycin (TU) and thapsigargin (TG)-induced ER stress. In …
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The anticipatory unfolded protein response and estrogen receptor mutations in breast cancer
… regulated gene expression. Knockdown of ATF6α or XBP1, which regulate UPR-induced chaperone production, inhibited EGF stimulated cell proliferation. These data highlight the importance of anticipatory UPR pathway in the normal actions of mitogenic hormones. Unlike EGFR which functions as a …
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Conserved temporal ordering of promoter activation implicates common mechanisms governing the immediate early response across cell types and stimuli
The promoters of immediate early genes (IEGs) are rapidly activated in response to an external stimulus. These genes, also known as primary response genes, have been identified in a range of cell types, under diverse extracellular signals and using varying experimental protocols. Genomic dissection …
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A Leap of Fate: Fluid identity, functional modules, and flexible strategies for transcription factor-based reprogramming
… an improvement on the existing method of XBP1 or PRDM1/BLIMP1 over-expression. Chapter 5 attempts to address how predictive framework might be adapted for the design of a truly synthetic cell type: a functionally defined target cell. It proposes the concept of a reprogramming dictionary, …
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Effects of prepartum dietary energy and lipid supplementation on hepatic transcriptome profiles in dairy cows during the transition period
… of ER and oxidative stress indicator genes XBP1, PERK, GRP94 and HSP40 was lower in OVE than CON but TRB3, HSPA1A, HSPA1B and CREB3L3 had greater (Diet × Time; P < 0.05) expression in OVE. Expression postpartum of the inflammatory genes NFKB1, RELA, CHUK, MYD88, TNF, SAA3, and PTX3 increased …