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molecular chaperone and endoplasmic reticulum

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https://www.readbyqxmd.com/read/27907150/molecular-characterization-of-two-monoclonal-antibodies-against-the-same-epitope-on-b-cell-receptor-associated-protein-31
#1
Won-Tae Kim, Saemina Shin, Hyo Jeong Hwang, Min Kyu Kim, Han-Sung Jung, Hwangseo Park, Chun Jeih Ryu
Previously, we showed that B-cell receptor associated protein 31 (BAP31), an endoplasmic reticulum (ER) membrane chaperone, is also expressed on the cell surface by two monoclonal antibodies (MAbs) 297-D4 and 144-A8. Both MAbs recognize the same linear epitope on the C-terminal domain of BAP31, although they were independently established. Here, flow cytometric analysis showed that 144-A8 had additional binding properties to some cells, as compared to 297-D4. Quantitative antigen binding assays also showed that 144-A8 had higher antigen binding capacity than 297-D4...
2016: PloS One
https://www.readbyqxmd.com/read/27903760/interactions-between-intersubunit-transmembrane-domains-regulate-the-chaperone-dependent-degradation-of-an-oligomeric-membrane-protein
#2
Teresa M Buck, Alexa S Jordahl, Megan E Yates, Mike Preston, Emily Cook, Thomas R Kleyman, Jeffrey L Brodsky
The Epithelial Sodium Channel (ENaC) in kidney regulates blood pressure through control of sodium and volume homeostasis, and in lung ENaC regulates the volume of airway and alveolar fluids.  ENaC is a heterotrimer of homologous α-, β-, and γ-subunits, and assembles in the Endoplasmic Reticulum (ER) before it traffics and functions at the plasma membrane. Improperly folded or orphaned ENaC subunits are subject to ER quality control and targeted for ER associated degradation (ERAD). We previously established that a conserved, ER lumenal, molecular chaperone, Lhs1/GRP170, selects αENaC, but not β- or γENaC, for degradation when the ENaC subunits were individually expressed...
November 30, 2016: Biochemical Journal
https://www.readbyqxmd.com/read/27869218/n-linked-glycosylation-at-asn152-on-cd147-affects-protein-folding-and-stability-promoting-tumour-metastasis-in-hepatocellular-carcinoma
#3
Jiang-Hua Li, Wan Huang, Peng Lin, Bo Wu, Zhi-Guang Fu, Hao-Miao Shen, Lin Jing, Zhen-Yu Liu, Yang Zhou, Yao Meng, Bao-Qing Xu, Zhi-Nan Chen, Jian-Li Jiang
Cluster of differentiation 147 (CD147), also known as extracellular matrix metalloproteinase inducer, is a transmembrane glycoprotein that mediates oncogenic processes partly through N-glycosylation modifications. N-glycosylation has been demonstrated to be instrumental for the regulation of CD147 function during malignant transformation. However, the role that site-specific glycosylation of CD147 plays in its defective function in hepatocellular carcinomacells needs to be determined. Here, we demonstrate that the modification of N-glycosylation at Asn152 on CD147 strongly promotes hepatocellular carcinoma (HCC) invasion and migration...
November 21, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27846717/-endoplasmic-reticulum-chaperones-at-the-tumor-cell-surface-and-in-the-extracellular-space
#4
V Brychtová, B Vojtěšek
BACKGROUND: Endoplasmic reticulum chaperones are stress induced proteins capable of translocation into cytosol, cell membrane or extracellular space. The chaperones are transported from the endoplasmic reticulum particularly under endoplasmic reticulum stress conditions, while their constitutive extracellular expression was found in many cancers. Cell surface or extracellular endoplasmic reticulum chaperones take up distinct functions compared to their endoplasmic reticulum resident variants because they act like multifunctional receptors and thus affect cell signaling and proliferation...
2016: Klinická Onkologie: Casopis Ceské a Slovenské Onkologické Spolecnosti
https://www.readbyqxmd.com/read/27844183/evaluation-and-treatment-of-endoplasmic-reticulum-er-stress-in-right-ventricular-dysfunction-during-monocrotaline-induced-rat-pulmonary-arterial-hypertension
#5
Jing-Jing Wang, Xiang-Rong Zuo, Jian Xu, Jin-Yong Zhou, Hui Kong, Xiao-Ning Zeng, Wei-Ping Xie, Quan Cao
PURPOSE: Endoplasmic reticulum (ER) stress contributes to pulmonary artery hypertension (PAH). However, the exact roles of ER stress in right ventricular (RV) dysfunction, which is strongly associated with PAH, are largely unknown. Here, we aimed to explore how ER stress affects RV function in a rat PAH model and evaluated the effects of an ER stress inhibitor on RV dysfunction. METHODS: We examined expression changes of an ER marker: chaperone glucose-regulated protein 78 (GRP78), three ER stress sensor proteins: activating transcription factor 6 (ATF6), inositol-requiring enzyme 1 (IRE1), and protein kinase RNA-like endoplasmic reticulum kinase (PERK), and a key ER stress-induced apoptosis indicator: CCAAT/enhancer-binding protein homologous protein (CHOP), with inflammation indicators: interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α), and matrix metalloproteinases (MMPs) in RV at 3, 7, 14 and 28 days following a single dose of monocrotaline (MCT) injection, with or without a preventive treatment [4-phenylbutyric acid (PBA)]...
November 14, 2016: Cardiovascular Drugs and Therapy
https://www.readbyqxmd.com/read/27843443/rna-interference-mediated-simultaneous-suppression-of-seed-storage-proteins-in-rice-grains
#6
Kyoungwon Cho, Hye-Jung Lee, Yeong-Min Jo, Sun-Hyung Lim, Randeep Rakwal, Jong-Yeol Lee, Young-Mi Kim
Seed storage proteins (SSPs) such as glutelin, prolamin, and globulin are abundant components in some of the most widely consumed food cereals in the world. Synthesized in the rough endoplasmic reticulum (ER), SSPs are translocated to the protein bodies. Prolamins are located at the spherical protein body I derived from the ER, whereas, glutelins and globulin are accumulated in the irregularly shaped protein bodies derived from vacuoles. Our previous studies have shown that the individual suppression of glutelins, 13-kDa prolamins and globulin caused the compensative accumulation of other SSPs...
2016: Frontiers in Plant Science
https://www.readbyqxmd.com/read/27819675/induction-of-endoplasmic-reticulum-stress-by-deletion-of-grp78-depletes-apc-mutant-intestinal-epithelial-stem-cells
#7
J F van Lidth de Jeude, B J Meijer, M C B Wielenga, C N Spaan, B Baan, S L Rosekrans, S Meisner, Y H Shen, A S Lee, J C Paton, A W Paton, V Muncan, G R van den Brink, J Heijmans
Intestinal epithelial stem cells are highly sensitive to differentiation induced by endoplasmic reticulum (ER) stress. Colorectal cancer develops from mutated intestinal epithelial stem cells. The most frequent initiating mutation occurs in Apc, which results in hyperactivated Wnt signalling. This causes hyperproliferation and reduced sensitivity to chemotherapy, but whether these mutated stem cells are sensitive to ER stress induced differentiation remains unknown. Here we examined this by generating mice in which both Apc and ER stress repressor chaperone Grp78 can be conditionally deleted from the intestinal epithelium...
November 7, 2016: Oncogene
https://www.readbyqxmd.com/read/27749824/translocon-component-sec62-acts-in-endoplasmic-reticulum-turnover-during-stress-recovery
#8
Fiorenza Fumagalli, Julia Noack, Timothy J Bergmann, Eduardo Cebollero, Giorgia Brambilla Pisoni, Elisa Fasana, Ilaria Fregno, Carmela Galli, Marisa Loi, Tatiana Soldà, Rocco D'Antuono, Andrea Raimondi, Martin Jung, Armin Melnyk, Stefan Schorr, Anne Schreiber, Luca Simonelli, Luca Varani, Caroline Wilson-Zbinden, Oliver Zerbe, Kay Hofmann, Matthias Peter, Manfredo Quadroni, Richard Zimmermann, Maurizio Molinari
The endoplasmic reticulum (ER) is a site of protein biogenesis in eukaryotic cells. Perturbing ER homeostasis activates stress programs collectively called the unfolded protein response (UPR). The UPR enhances production of ER-resident chaperones and enzymes to reduce the burden of misfolded proteins. On resolution of ER stress, ill-defined, selective autophagic programs remove excess ER components. Here we identify Sec62, a constituent of the translocon complex regulating protein import in the mammalian ER, as an ER-resident autophagy receptor...
November 2016: Nature Cell Biology
https://www.readbyqxmd.com/read/27720586/endoplasmic-reticulum-proteostasis-influences-the-oligomeric-state-of-an-amyloidogenic-protein-secreted-from-mammalian-cells
#9
John J Chen, Joseph C Genereux, Eul Hyun Suh, Vincent F Vartabedian, Bibiana Rius, Song Qu, Maria T A Dendle, Jeffery W Kelly, R Luke Wiseman
Transthyretin (TTR) is a tetrameric serum protein associated with multiple systemic amyloid diseases. In these disorders, TTR aggregates in extracellular environments through a mechanism involving rate-limiting dissociation of the tetramer to monomers, which then misfold and aggregate into soluble oligomers and amyloid fibrils that induce toxicity in distal tissues. Using an assay established herein, we show that highly destabilized, aggregation-prone TTR variants are secreted as both native tetramers and non-native conformations that accumulate as high-molecular-weight oligomers...
October 20, 2016: Cell Chemical Biology
https://www.readbyqxmd.com/read/27707963/disruption-of-protein-processing-in-the-endoplasmic-reticulum-of-dyt1-knock-in-mice-implicates-novel-pathways-in-dystonia-pathogenesis
#10
Genevieve Beauvais, Nicole M Bode, Jaime L Watson, Hsiang Wen, Kevin A Glenn, Hiroyuki Kawano, N Charles Harata, Michelle E Ehrlich, Pedro Gonzalez-Alegre
: Dystonia type 1 (DYT1) is a dominantly inherited neurological disease caused by mutations in TOR1A, the gene encoding the endoplasmic reticulum (ER)-resident protein torsinA. Previous work mostly completed in cell-based systems suggests that mutant torsinA alters protein processing in the secretory pathway. We hypothesized that inducing ER stress in the mammalian brain in vivo would trigger or exacerbate mutant torsinA-induced dysfunction. To test this hypothesis, we crossed DYT1 knock-in with p58(IPK)-null mice...
October 5, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27694578/redox-assisted-regulation-of-ca2-homeostasis-in-the-endoplasmic-reticulum-by-disulfide-reductase-erdj5
#11
Ryo Ushioda, Akitoshi Miyamoto, Michio Inoue, Satoshi Watanabe, Masaki Okumura, Ken-Ichi Maegawa, Kaiku Uegaki, Shohei Fujii, Yasuko Fukuda, Masataka Umitsu, Junichi Takagi, Kenji Inaba, Katsuhiko Mikoshiba, Kazuhiro Nagata
Calcium ion (Ca(2+)) is an important second messenger that regulates numerous cellular functions. Intracellular Ca(2+) concentration ([Ca(2+)]i) is strictly controlled by Ca(2+) channels and pumps on the endoplasmic reticulum (ER) and plasma membranes. The ER calcium pump, sarco/endoplasmic reticulum calcium ATPase (SERCA), imports Ca(2+) from the cytosol into the ER in an ATPase activity-dependent manner. The activity of SERCA2b, the ubiquitous isoform of SERCA, is negatively regulated by disulfide bond formation between two luminal cysteines...
October 11, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27679419/tumor-associated-antigens-tn-antigen-stn-antigen-and-t-antigen
#12
REVIEW
C Fu, H Zhao, Y Wang, H Cai, Y Xiao, Y Zeng, H Chen
Glycosylation is one of the major posttranslational modifications of proteins. N-glycosylation (Asn-linked) and O-glycosylation (Ser/Thr-linked) are the two main forms. Abnormal O-glycosylation is frequently observed on the surface of tumor cells, and is associated with an adverse outcome and poor prognosis in patients with cancer. O-glycans (Tn, sTn, and T antigen) can be synthesized in the Golgi apparatus with the aid of several glycosyltransferases (such as T-synthase and ST6GalNAc-I) in a suitable environment...
December 2016: HLA
https://www.readbyqxmd.com/read/27667530/5-n-ethylcarboxamidoadenosine-is-not-a-paralog-specific-hsp90-inhibitor
#13
Shanshan Liu, Timothy O Street
The molecular chaperone Hsp90 facilitates the folding and modulates activation of diverse substrate proteins. Unlike other heat shock proteins such as Hsp60 and Hsp70, Hsp90 plays critical regulatory roles by maintaining active states of kinases, many of which are overactive in cancer cells. Four Hsp90 paralogs are expressed in eukaryotic cells: Hsp90α/β (in the cytosol), Grp94 (in the endoplasmic reticulum), Trap1 (in mitochondria). Although numerous Hsp90 inhibitors are being tested in cancer clinical trials, little is known about why different Hsp90 inhibitors show specificity among Hsp90 paralogs...
December 2016: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/27639166/formaldehyde-is-a-potent-proteotoxic-stressor-causing-rapid-heat-shock-factor-protein-1-activation-and-lys48-linked-polyubiquitination-of-proteins
#14
Sara Ortega-Atienza, Blazej Rubis, Caitlin McCarthy, Anatoly Zhitkovich
Endogenous and exogenous formaldehyde (FA) has been linked to cancer, neurotoxicity, and other pathophysiologic effects. Molecular and cellular mechanisms that underlie FA-induced damage are poorly understood. In this study, we investigated whether proteotoxicity is an important, unrecognized factor in cell injury caused by FA. We found that irrespective of their cell cycle phases, all FA-treated human cells rapidly accumulated large amounts of proteins with proteasome-targeting K48-linked polyubiquitin, which was comparable with levels of polyubiquitination in proteasome-inhibited MG132 controls...
September 14, 2016: American Journal of Pathology
https://www.readbyqxmd.com/read/27635664/an-11-mer-amyloid-beta-peptide-fragment-provokes-chemical-mutations-and-parkinsonian-biomarker-aggregation-in-dopaminergic-cells-a-novel-road-map-for-transfected-parkinson-s
#15
Parijat Kabiraj, Jose Eduardo Marin, Armando Varela-Ramirez, Mahesh Narayan
Amyloid beta (Aβ) aggregation is generally associated with Alzheimer's onset. Here, we demonstrate that incubation of dopaminergic SH-SY5Y cells with an Aβ peptide fragment (an 11-mer composed of residues 25-35; Aβ (25-35)) results in elevated intracellular nitrosative stress and induces chemical mutation of protein disulfide isomerase (PDI), an endoplasmic reticulum-resident oxidoreductase chaperone. Furthermore, Aβ (25-35) provokes aggregation of both the minor and major biomarkers of Parkinson's disease, namely, synphilin-1 and α-synuclein, respectively...
October 3, 2016: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/27634156/glucose-regulated-protein-78-contributes-to-the-proliferation-and-tumorigenesis-of-human-colorectal-carcinoma-via-akt-and-erk-pathways
#16
Xuan Zhou, Xiaoming Xing, Shuping Zhang, Lili Liu, Chengqin Wang, Lin Li, Qiuxia Ji, Huamin Liu
Glucose-regulated protein 78 (GRP78), a molecular chaperon in the endoplasmic reticulum (ER), is overexpressed in a variety of tumor types and plays a critical role in cancer cell proliferation, migration, invasion and drug resistance. However, the mechanisms underlying the role of GRP78 in tumor carcinogenesis remain largely unknown. In the present study, we found that GRP78 knockdown in colorectal carcinoma (CRC) cells significantly inhibited cell proliferation, colony formation and tumorigenesis in vitro and in vivo...
September 16, 2016: Oncology Reports
https://www.readbyqxmd.com/read/27629591/unique-roles-of-the-unfolded-protein-response-pathway-in-fungal-development-and-differentiation
#17
Kwang-Woo Jung, Yee-Seul So, Yong-Sun Bahn
Cryptococcus neoformans, a global fungal meningitis pathogen, employs the unfolded protein response pathway. This pathway, which consists of an evolutionarily conserved Ire1 kinase/endoribonuclease and a unique transcription factor (Hxl1), modulates the endoplasmic reticulum stress response and pathogenicity. Here, we report that the unfolded protein response pathway governs sexual and unisexual differentiation of C. neoformans in an Ire1-dependent but Hxl1-independent manner. The ire1∆ mutants showed defects in sexual mating, with reduced cell fusion and pheromone-mediated formation of the conjugation tube...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27628049/synergistic-effect-of-fenretinide-and-curcumin-for-treatment-of-non-small-cell-lung-cancer
#18
Huanxian Chen, Linmin Chen, Liang Wang, Xinhua Zhou, Judy Yuet-Wa Chan, Jingjing Li, Guozhen Cui, Simon Ming-Yuen Lee
Curcumin and fenretinide are 2 well-known and promising chemotherapeutic compounds via various molecular mechanisms. However, the anticancer capacity of either curcumin or fenretinide is limited. This prompted us to examine the combined anticancer effects of curcumin and fenretinide. Our results demonstrate for the first time that there is synergistic anticancer effect of combined treatment with these 2 agents, leading to enhanced cytotoxicity and enhanced expression level of pro-apoptotic protein cleaved PARP in non-small cell lung cancer (NSCLC) cells while showed little toxicity to rat cardiomyoblast normal cells...
August 11, 2016: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/27619675/does-native-trypanosoma-cruzi-calreticulin-mediate-growth-inhibition-of-a-mammary-tumor-during-infection
#19
Paula Abello-Cáceres, Javier Pizarro-Bauerle, Carlos Rosas, Ismael Maldonado, Lorena Aguilar-Guzmán, Carlos González, Galia Ramírez, Jorge Ferreira, Arturo Ferreira
BACKGROUND: For several decades now an antagonism between Trypanosoma cruzi infection and tumor development has been detected. The molecular basis of this phenomenon remained basically unknown until our proposal that T. cruzi Calreticulin (TcCRT), an endoplasmic reticulum-resident chaperone, translocated-externalized by the parasite, may mediate at least an important part of this effect. Thus, recombinant TcCRT (rTcCRT) has important in vivo antiangiogenic and antitumor activities. However, the relevant question whether the in vivo antitumor effect of T...
2016: BMC Cancer
https://www.readbyqxmd.com/read/27609520/hiv-1-tat-induces-unfolded-protein-response-and-endoplasmic-reticulum-stress-in-astrocytes-and-causes-neurotoxicity-through-glial-fibrillary-acidic-protein-gfap-activation-and-aggregation
#20
Yan Fan, Johnny J He
HIV-1 Tat is a major culprit for HIV/neuroAIDS. One of the consistent hallmarks of HIV/neuroAIDS is reactive astrocytes or astrocytosis, characterized by increased cytoplasmic accumulation of the intermediate filament glial fibrillary acidic protein (GFAP). We have shown that that Tat induces GFAP expression in astrocytes and that GFAP activation is indispensable for astrocyte-mediated Tat neurotoxicity. However, the underlying molecular mechanisms are not known. In this study, we showed that Tat expression or GFAP expression led to formation of GFAP aggregates and induction of unfolded protein response (UPR) and endoplasmic reticulum (ER) stress in astrocytes...
October 21, 2016: Journal of Biological Chemistry
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