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https://www.readbyqxmd.com/read/28093457/functional-analysis-of-the-mammalian-rna-ligase-for-ire1-in-the-unfolded-protein-response
#1
Juthakorn Poothong, Witoon Tirasophon, Randal J Kaufman
The unfolded protein response (UPR) is a conserved signaling pathway activated upon the accumulation of unfolded proteins within the endoplasmic reticulum (ER), termed ER stress. Upon ER stress, HAC1 / XBP1 undergoes exon/intron specific excision by IRE1 to remove an intron and liberate the 5' and 3' exons. In yeast, the 5' and 3' HAC1 exons are subsequently ligated by tRNA ligase (Rlg1p) whereas XBP1 ligation in mammalian cells is catalyzed by a recently identified ligase, RtcB. In this study, the RNA ligase activity of the human RtcB involved in the unconventional splicing of XBP1 / HAC1 mRNA was explored in an rlg1-100 mutant yeast strain...
January 16, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/28079229/the-transcription-factor-xbp1-in-memory-and-cognition-implications-in-alzheimer-disease
#2
Moustapha Cissé, Eric Duplan, Frédéric Checler
X-box binding protein 1 (XBP1) is a unique basic region leucine zipper transcription factor isolated two decades ago in a search for regulators of major histocompatibility complex class II gene expression. XBP1 is a very complex protein regulating many physiological functions, including immune system, inflammatory responses, and lipid metabolism. Evidence over the past few years suggests that XBP1 also plays important roles in pathological settings since its activity as transcription factor has profound effects on the prognosis and progression of diseases such as cancer, neurodegeneration, and diabetes...
January 4, 2017: Molecular Medicine
https://www.readbyqxmd.com/read/28065589/perk-and-xbp1-differentially-regulate-cxcl10-and-ccl2-production
#3
Shuang Zhu, Hua Liu, Haibo Sha, Ling Qi, Dian-Shuai Gao, Wenbo Zhang
Inflammation plays a key role in the pathogenesis of many retinal degenerative diseases related with photoreceptor dysfunction/degeneration. However the involvement of photoreceptor cells in inflammatory reactions is largely unknown as they are not considered as inflammatory cells. In this study, we assessed whether photoreceptor cells can produce CCL2 and CXCL10, two important players in inflammation during endoplasmic reticulum (ER) stress. After photoreceptor 661 W cells were treated with ER stress inducer thapsigargin (TG), induction of ER stress increased CXCL10 and CCL2 expression at both mRNA and protein levels, which was significantly blocked by an ER stress blocker 4-phenylbutyrate...
January 5, 2017: Experimental Eye Research
https://www.readbyqxmd.com/read/28052118/tgf-%C3%AE-3-inhibits-antibody-production-by-human-b-cells
#4
Yumi Tsuchida, Shuji Sumitomo, Kazuyoshi Ishigaki, Akari Suzuki, Yuta Kochi, Haruka Tsuchiya, Mineto Ota, Toshihiko Komai, Mariko Inoue, Kaoru Morita, Tomohisa Okamura, Kazuhiko Yamamoto, Keishi Fujio
TGF-β is a pleotropic cytokine involved in various biological processes. Of the three isoforms of TGF-β, TGF-β1 has long been recognized as an important inhibitory cytokine in the immune system and has been reported to inhibit B cell function in both mice and humans. Recently, it has been suggested that TGF-β3 may play an important role in the regulation of immune system in mice. Murine CD4+CD25-LAG3+ regulatory T cells suppress B cell function through the production of TGF-β3, and it has been reported that TGF-β3 is therapeutic in a mouse model of systemic lupus erythematosus...
2017: PloS One
https://www.readbyqxmd.com/read/28049460/bitter-melon-protects-against-er-stress-in-ls174t-colonic-epithelial-cells
#5
Dale A Kunde, Wai Chin Chong, Prathiba V Nerurkar, Kiran D K Ahuja, Jeremy Just, Jason A Smith, Nuri Guven, Rajaraman D Eri
BACKGROUND: Bitter Melon (BM) has been used as a functional food in traditional Chinese and Indian medicine for many generations and has gained a great deal of attention due to its apparent benefits in moderating some of the pathogenic processes in a variety of inflammatory conditions. BM extract (BME) has been shown to possess strong anti-oxidant properties. In addition, it can ameliorate oxidative stress and potentially ER stress. There is increasing evidence that oxidative and ER stress are major contributors for intestinal secretory cell dysfunction which leads to local inflammation and disease pathogenesis that are hallmarks of inflammatory bowel diseases (IBD)...
January 3, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28039913/the-unfolded-protein-response-mediates-fibrogenesis-and-collagen-i-secretion-through-regulating-tango1-in-mice
#6
Jessica L Maiers, Enis Kostallari, Malek Mushref, Thiago M deAssuncao, Haiyang Li, Nidhi Jalan-Sakrikar, Robert C Huebert, Sheng Cao, Harmeet Malhi, Vijay H Shah
: Fibrogenesis encompasses the deposition of matrix proteins, such as collagen I, by hepatic stellate cells (HSCs) that culminates in cirrhosis. Fibrogenic signals drive transcription of procollagen I, which enters the endoplasmic reticulum (ER), is trafficked through the secretory pathway, and released to generate extracellular matrix. Alternatively, disruption of procollagen I ER export could activate the unfolded protein response (UPR) and drive HSC apoptosis. Using a small interfering RNA screen, we identified Transport and Golgi organization 1 (TANGO1) as a potential participant in collagen I secretion...
November 5, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28039331/hepatic-deletion-of-x-box-binding-protein-1-impairs-bile-acid-metabolism-in-mice
#7
Xiaoying Liu, Anne S Henkel, Brian E LeCuyer, Susan C Hubchak, Matthew J Schipma, Eric Zhang, Richard M Green
The unfolded protein response (UPR) is an adaptive response to endoplasmic reticulum stress and the inositol-requiring enzyme 1α/X-box binding protein 1 (IRE1α/XBP1) pathway of the UPR is important in lipid metabolism. However, its role in bile acid metabolism remains unknown. We demonstrate that liver-specific Xbp1 knockout (LS-Xbp1(-/-)) mice had a 45% reduction in total bile acid pool. LS-Xbp1(-/-) mice had lower serum 7α-hydroxy-4-cholesten-3-one (C4) levels compared to Xbp1(fl/fl) mice, indicating reduced CYP7A1 synthetic activity...
December 30, 2016: Journal of Lipid Research
https://www.readbyqxmd.com/read/28029742/functional-interaction-of-erap2-and-hla-b27-activates-the-unfolded-protein-response
#8
Zhenbo Zhang, Francesco Ciccia, Fanxing Zeng, Giuliana Guggino, Kirby Yee, Hasan Abdullah, Mark S Silverberg, Riccardo Alessandro, Giovanni Triolo, Nigil Haroon
OBJECTIVES: The basic mechanisms underlying ankylosing spondylitis (AS) pathogenesis remain unresolved. We previously reported an association of the single nucleotide polymorphisms (SNP) rs2549782 in Endoplasmic Reticulum Aminopeptidase 2 (ERAP2) with AS. It is known that patients homozygous for the G allele (GG) of another ERAP2 SNP rs2248374 have no ERAP2 expression (ERAP2-null). We utilized this information to study the impact of ERAP2 deficiency on HLA-B27 expression in AS patients...
December 28, 2016: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/28028927/foxc1-is-associated-with-estrogen-receptor-alpha-and-affects-sensitivity-of-tamoxifen-treatment-in-breast-cancer
#9
Jinhua Wang, Yali Xu, Li Li, Lin Wang, Ru Yao, Qiang Sun, Guanhua Du
FOXC1 is a member of Forkhead box transcription factors that participates in embryonic development and tumorigenesis. Our previous study demonstrated that FOXC1 was highly expressed in triple-negative breast cancer. However, it remains unclear what is the relation between FOXC1 and ERα and if FOXC1 regulates expression of ERα. To explore relation between FOXC1 and ERα and discover regulation of ERα expression by FOXC1 in breast cancer, we analyzed data assembled in the Oncomine and TCGA, and found that there was significantly higher FOXC1 expression in estrogen receptor-negative breast cancer than that in estrogen receptor-positive breast cancer...
December 28, 2016: Cancer Medicine
https://www.readbyqxmd.com/read/27996033/the-xbp1-arm-of-the-unfolded-protein-response-induces-fibrogenic-activity-in-hepatic-stellate-cells-through-autophagy
#10
Rosa S Kim, Daisuke Hasegawa, Nicolas Goossens, Takuma Tsuchida, Varinder Athwal, Xiaochen Sun, Christopher L Robinson, Dipankar Bhattacharya, Hsin-I Chou, David Y Zhang, Bryan C Fuchs, Youngmin Lee, Yujin Hoshida, Scott L Friedman
Autophagy and the unfolded protein response (UPR) both promote activation of hepatic stellate cells (HSC), however the link between the two stimuli remains unclear. Here we have explored the role of X-box binding protein 1 (XBP1), one of three UPR effector pathways and sought to establish the interdependence between autophagy and the UPR during HSC activation. XBP1 induction accompanied both culture-based HSC activation and ER stress induced by tunicamycin. Ectopic overexpression of XBP1 induced collagen 1-alpha expression in HSCs, which was inhibited by knockdown of ATG7, a critical autophagy mediator...
December 20, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27993609/chlorpyrifos-induces-endoplasmic-reticulum-stress-in-jeg-3-cells
#11
Luciana Reyna, Jésica Flores-Martín, Magali E Ridano, Graciela M Panzetta-Dutari, Susana Genti-Raimondi
Chlorpyrifos (CPF) is an organophosphorous pesticide widely used in agricultural, industrial, and household applications. We have previously shown that JEG-3 cells are able to attenuate the oxidative stress induced by CPF through the adaptive activation of the Nrf2/ARE pathway. Considering that there is a relationship between oxidative stress and endoplasmic reticulum stress (ER), herein we investigated whether CPF also induces ER stress in JEG-3 cells. Cells were exposed to 50μM or 100μM CPF during 24h in conditions where cell viability was not altered...
December 16, 2016: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/27973418/varicella-zoster-virus-infectious-cycle-er-stress-autophagic-flux-and-amphisome-mediated-trafficking
#12
REVIEW
Charles Grose, Erin M Buckingham, John E Carpenter, Jeremy P Kunkel
Varicella-zoster virus (VZV) induces abundant autophagy. Of the nine human herpesviruses, the VZV genome is the smallest (~124 kbp), lacking any known inhibitors of autophagy, such as the herpes simplex virus ICP34.5 neurovirulence gene. Therefore, this review assesses the evidence for VZV-induced cellular stress, endoplasmic-reticulum-associated degradation (ERAD), and autophagic flux during the VZV infectious cycle. Even though VZV is difficult to propagate in cell culture, the biosynthesis of the both N- and O-linked viral glycoproteins was found to be abundant...
December 10, 2016: Pathogens
https://www.readbyqxmd.com/read/27959929/histological-transformation-and-progression-in-follicular-lymphoma-a-clonal-evolution-study
#13
Robert Kridel, Fong Chun Chan, Anja Mottok, Merrill Boyle, Pedro Farinha, King Tan, Barbara Meissner, Ali Bashashati, Andrew McPherson, Andrew Roth, Karey Shumansky, Damian Yap, Susana Ben-Neriah, Jamie Rosner, Maia A Smith, Cydney Nielsen, Eva Giné, Adele Telenius, Daisuke Ennishi, Andrew Mungall, Richard Moore, Ryan D Morin, Nathalie A Johnson, Laurie H Sehn, Thomas Tousseyn, Ahmet Dogan, Joseph M Connors, David W Scott, Christian Steidl, Marco A Marra, Randy D Gascoyne, Sohrab P Shah
BACKGROUND: Follicular lymphoma (FL) is an indolent, yet incurable B cell malignancy. A subset of patients experience an increased mortality rate driven by two distinct clinical end points: histological transformation and early progression after immunochemotherapy. The nature of tumor clonal dynamics leading to these clinical end points is poorly understood, and previously determined genetic alterations do not explain the majority of transformed cases or accurately predict early progressive disease...
December 2016: PLoS Medicine
https://www.readbyqxmd.com/read/27932618/the-roles-of-unfolded-protein-response-pathways-in-chlamydia-pathogenesis
#14
Zenas George, Yusuf Omosun, Anthony A Azenabor, James Partin, Kahaliah Joseph, Debra Ellerson, Qing He, Francis Eko, Claudiu Bandea, Pavel Svoboda, Jan Pohl, Carolyn M Black, Joseph U Igietseme
Chlamydia is an obligate intracellular bacterium that relies on host cell for essential nutrients and ATP for a productive infection. Although the unfolded protein response (UPR) plays a major role in certain microbial infectivity, its role in chlamydial pathogenesis is unknown. We hypothesized that Chlamydia induces UPR and exploits it to upregulate host cell uptake and metabolism of glucose, production of ATP, phospholipids and other molecules required for its replicative development and host survival. Using a combination of biochemical and pathway inhibition assays, we showed that the three UPR pathway transducers: Protein kinase RNA-activated (PKR)-like ER kinase (PERK), Inositol-requiring enzyme-1α (IRE1α), and Activating transcription factor-6α (ATF6α) were activated during Chlamydia infection...
December 8, 2016: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/27929749/critical-role-of-x-box-binding-protein-1-in-nadph-oxidase-4-triggered-cardiac-hypertrophy-is-mediated-by-receptor-interacting-protein-kinase-1
#15
Li Chen, Mingyue Zhao, Junli Li, Yu Wang, Qinxue Bao, Siyuan Wu, Xueqin Deng, Xiaoju Tang, Wenchao Wu, Xiaojing Liu
NADPH oxidase 4 (NOX4) and the NOX4-related redox signaling are implicated in cardiac hypertrophy. NOX4 is interrelated with endoplasmic reticulum stress (ERS). Spliced X-box binding protein 1 (Xbp1s) is a key mediator of ERS while its role in cardiac hypertrophy is still poorly understood. Recently, receptor interacting protein kinase 1(RIPK1) has been increasingly reported to be associated with ERS. Therefore, we aimed to test the hypothesis that Xbp1s mediates NOX4-triggered cardiac hypertrophy via RIPK1 signaling...
December 8, 2016: Cell Cycle
https://www.readbyqxmd.com/read/27928013/herpes-simplex-virus-1-ul41-protein-suppresses-the-ire1-xbp1-signal-pathway-of-the-unfolded-protein-response-via-its-rnase-activity
#16
Pengchao Zhang, Chenhe Su, Zhangtao Jiang, Chunfu Zheng
: During viral infection, accumulation of viral proteins can cause stress in the endoplasmic reticulum (ER) and trigger the unfolded protein response (UPR) to restore the ER homeostasis. Inositol-requiring enzyme 1 (IRE1)-dependent pathway is the most conserved one of the three UPR signal pathways. Upon activation, IRE1 splices out an intron from the unspliced inactive form X-box binding protein 1 (XBP1(u)) mRNA and produces a transcriptionally potent spliced form (XBP1(s)). Previous studies have reported that the IRE1/XBP1 pathway is inhibited upon herpes simplex virus 1 (HSV-1) infection, however, the underlying molecular mechanism is still illusive...
December 7, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27897229/global-gene-regulation-during-activation-of-immunoglobulin-class-switching-in-human-b-cells
#17
Youming Zhang, David J Fear, Saffron A G Willis-Owen, William O Cookson, Miriam F Moffatt
Immunoglobulin class switch recombination (CSR) to IgE is a tightly regulated process central to atopic disease. To profile the B-cell transcriptional responses underlying the activation of the germinal centre activities leading to the generation of IgE, naïve human B-cells were stimulated with IL-4 and anti-CD40. Gene expression and alternative splicing were profiled over 12 days using the Affymetrix Human Exon 1.0 ST Array. A total of 1,399 genes, forming 13 temporal profiles were differentially expressed...
November 29, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27895727/deficiency-of-sumo-specific-protease-1-induces-arsenic-trioxide-mediated-apoptosis-by-regulating-xbp1-activity-in-human-acute-promyelocytic-leukemia
#18
Fei-Fei Wang, Ming-Zhu Liu, Yi Sui, Qing Cao, Bo Yan, Mei-Ling Jin, Xi Mo
Small ubiquitin-like modifier (SUMO)/sentrin-specific protease 1 (SENP1), a member of the SENP family, is highly expressed in several neoplastic tissues. However, the effect of SENP1 in acute promyelocytic leukemia (APL) has not been elucidated. In the present study, it was observed that SENP1 deficiency had no effect on the spontaneous apoptosis or differentiation of NB4 cells. Arsenic trioxide (As2O3) could induce the upregulation of endoplasmic reticulum (ER) stress, resulting in the apoptosis of NB4 cells...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27863885/cell-type-specific-variation-in-the-induction-of-er-stress-and-downstream-events-in-chikungunya-virus-infection
#19
Sarawut Khongwichit, Nitwara Wikan, Bizunesh Abere, Chutima Thepparit, Atichat Kuadkitkan, Sukathida Ubol, Duncan R Smith
Over the last decade infections with the mosquito transmitted chikungunya virus (CHIKV) have become a major worldwide concern, and considerable efforts have been made in understanding the interaction of this virus with the host cell machinery. Studies have documented the induction of the unfolded protein response (UPR), as well as the induction of apoptosis and autophagy in response to CHIKV infection. This study comparatively analysed these three processes in two cell lines, Hela and HepG2. Infection of Hela cells was characterized by activation of the PERK/eIF2α branch of the UPR, the induction of autophagy and early apoptosis, while infection of HepG2 cells was characterized by activation of the IRE/XBP1 branch of the UPR, limited or no activation of autophagy and comparatively later apoptosis...
December 2016: Microbial Pathogenesis
https://www.readbyqxmd.com/read/27853103/endoplasmic-reticulum-stress-is-involved-in-2-4-dichlorophenol-induced-hepatotoxicity
#20
Jianbo Fu, Xiaoning Zhang, Peng Chen, Yingmei Zhang
2,4-Dichlorophenol (2,4-DCP) is an environmental pollutant exhibiting a wide spectrum of toxic effects. We investigated the toxic effects and potential mechanisms underlying 2,4-DCP-induced hepatotoxicity. In vitro, 2,4-DCP caused hepatotoxicity manifested by a decrease in cell viability and inhibition of colony formation. Bip and CHOP expression was up-regulated at the mRNA and protein levels. Moreover, 2,4-DCP induced eIF2α phosphorylation and Xbp1 mRNA splicing, indicating that endoplasmic reticulum (ER) stress was activated after exposure of HL7702 cells to 2,4-DCP for 12 hr...
2016: Journal of Toxicological Sciences
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