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https://www.readbyqxmd.com/read/28192616/association-of-ormdl3-with-rhinovirus-induced-endoplasmic-reticulum-stress-and-type-i-interferon-responses-in-human-leukocytes
#1
Yi-Ping Liu, Victoria Rajamanikham, Marissa Baron, Sagar Patel, Sameer K Mathur, Elizabeth A Schwantes, Carole Ober, Daniel J Jackson, James E Gern, Robert F Lemanske, Judith A Smith
BACKGROUND: Children with risk alleles at the 17q21 genetic locus who wheeze during rhinovirus illnesses have a greatly increased likelihood of developing childhood asthma. In mice, overexpression of the 17q21 gene ORMDL3 leads to airway remodeling and hyper-responsiveness. However, the mechanisms by which ORMDL3 predisposes to asthma are unclear. Previous studies have suggested that ORMDL3 induces endoplasmic reticulum (ER) stress and production of the type I interferon (IFN) regulated chemokine CXCL10...
February 13, 2017: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28190459/mutations-in-inpp5k-cause-a-form-of-congenital-muscular-dystrophy-overlapping-marinesco-sj%C3%A3-gren-syndrome-and-dystroglycanopathy
#2
Daniel P S Osborn, Heather L Pond, Neda Mazaheri, Jeremy Dejardin, Christopher J Munn, Khaloob Mushref, Edmund S Cauley, Isabella Moroni, Maria Barbara Pasanisi, Elizabeth A Sellars, R Sean Hill, Jennifer N Partlow, Rebecca K Willaert, Jaipreet Bharj, Reza Azizi Malamiri, Hamid Galehdari, Gholamreza Shariati, Reza Maroofian, Marina Mora, Laura E Swan, Thomas Voit, Francesco J Conti, Yalda Jamshidi, M Chiara Manzini
Congenital muscular dystrophies display a wide phenotypic and genetic heterogeneity. The combination of clinical, biochemical, and molecular genetic findings must be considered to obtain the precise diagnosis and provide appropriate genetic counselling. Here we report five individuals from four families presenting with variable clinical features including muscular dystrophy with a reduction in dystroglycan glycosylation, short stature, intellectual disability, and cataracts, overlapping both the dystroglycanopathies and Marinesco-Sjögren syndrome...
February 1, 2017: American Journal of Human Genetics
https://www.readbyqxmd.com/read/28160139/erratum-to-e1a-mediated-inhibition-of-hspa5-suppresses-cell-migration-and-invasion-in-triple-negative-breast-cancer
#3
Hsin-An Chen, Yi-Wen Chang, Chi-Feng Tseng, Ching-Feng Chiu, Chih-Chen Hong, Weu Wang, Ming-Yang Wang, Michael Hsiao, Jui-Ti Ma, Chung-Hsing Chen, Shih-Sheng Jiang, Chih-Hsiung Wu, Mien-Chie Hung, Ming-Te Huang, Jen-Liang Su
No abstract text is available yet for this article.
February 3, 2017: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/28148733/dynamic-interaction-and-phospho-proteomics-reveal-lck-as-a-major-signaling-hub-of-cd147-in-t-cells
#4
Verena Supper, Ingrid Hartl, Cyril Boulègue, Anna Ohradanova-Repic, Hannes Stockinger
Numerous publications have addressed CD147 as a tumor marker and regulator of cytoskeleton, cell growth, stress response, or immune cell function; however, the molecular functionality of CD147 remains incompletely understood. Using affinity purification, mass spectrometry, and phosphopeptide enrichment of isotope-labeled peptides, we examined the dynamic of the CD147 microenvironment and the CD147-dependent phosphoproteome in the Jurkat T cell line upon treatment with T cell stimulating agents. We identified novel dynamic interaction partners of CD147 such as CD45, CD47, GNAI2, Lck, RAP1B, and VAT1 and, furthermore, found 76 CD147-dependent phosphorylation sites on 57 proteins...
February 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28130223/hspa5-regulates-ferroptotic-cell-death-in-cancer-cells
#5
Shan Zhu, Qiuhong Zhang, Xiaofang Sun, Herbert J Zeh, Michael T Lotze, Rui Kang, Daolin Tang
Ferroptosis is a form of regulated cell death driven by oxidative injury promoting lipid peroxidation, although detailed molecular regulators are largely unknown. Here we show that heat shock 70kDa protein 5 (HSPA5) negatively regulates ferroptosis in human pancreatic ductal adenocarcinoma (PDAC) cells. Mechanistically, activating transcription factor 4 (ATF4) resulted in the induction of HSPA5, which in turn bound glutathione peroxidase 4 (GPX4) and protected against GPX4 protein degradation and subsequent lipid peroxidation...
January 27, 2017: Cancer Research
https://www.readbyqxmd.com/read/28115289/profibrotic-ihg-1-complexes-with-renal-disease-associated-hspa5-and-trap1-in-mitochondria
#6
Una Bhreathnach, Brenda Griffin, Eoin Brennan, Leah Ewart, Debra Higgins, Madeline Murphy
The highly conserved mitochondrial protein induced in high glucose-1 (IHG-1) functions to maintain mitochondrial quality and is associated with the development of fibrosis in diabetic nephropathy. Towards identifying novel approaches to treating diabetic kidney disease, IHG-1-protein-protein interactions were investigated using epitope-tagged immunoprecipitation analyses followed by mass spectrometry. Here we show that IHG-1 is solely expressed in mitochondria and localised to the inner mitochondrial membrane, the region where mitochondrial reactive oxygen species are generated...
January 20, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28110670/galnt6-stabilizes-grp78-protein-by-o-glycosylation-and-enhances-its-activity-to-suppress-apoptosis-under-stress-condition
#7
Jiaying Lin, Suyoun Chung, Koji Ueda, Koichi Matsuda, Yusuke Nakamura, Jae-Hyun Park
We previously reported that overexpression of an O-type glycosyltransferase, GALNT6 (polypeptide N-acetylgalactosaminyltransferase 6) played critical roles in mammary carcinogenesis. To further investigate the biological function of GALNT6, we screened a substrate protein(s) of GALNT6 using a VVA (Vicia villosa agglutinin) lectin (specific to GalNAc-Ser/Thr) pull-down method followed by mass spectrometry analysis. Here we report GRP78 (glucose-regulated protein 78, also known as HSPA5, heat shock 70 kDa protein 5), which is highly expressed in cancer cells and indicated to play important roles in various cellular processes including ER (endoplasmic reticulum) stress and autophagy, as a novel substrate of GALNT6...
January 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/27892644/saliva-protein-biomarkers-to-detect-oral-squamous-cell-carcinoma-oscc
#8
R Nagler
In a recent study published in the Proceedings of the National Academy of Sciences of the U.S.A., Jau-Song Yu et al reported of their generated four-protein biomarker panel consisting of MMP1, KNG1, ANXA2, and HSPA5, as based on a risk-score scheme they established (Yu et al, 2016). This panel showed high sensitivity (87.5%) and specificity (80.5%) values in a test set to distinguish OSCC patients' saliva samples from non-OSCC patients' saliva samples. The risk score >0.4 detected 84% of the stage I OSCCs and a significant portion (42%) of the high-risk, visible, oral potentially-malignant disorders (OPMDs)...
November 28, 2016: Oral Diseases
https://www.readbyqxmd.com/read/27881906/genetic-and-immunohistochemical-analysis-of-hspa5-in-mouse-and-human-retinas
#9
Sumana R Chintalapudi, XiaoFei Wang, Huiling Li, Yin H Chan Lau, Robert W Williams, Monica M Jablonski
PURPOSE: Photoreceptor degenerative diseases are among the leading causes of vision loss. Although the causative genetic mutations are often known, mechanisms leading to photoreceptor degeneration remain poorly defined. We have previously demonstrated that the photoreceptor membrane-associated protein XAP-1 antigen is a product of the HSPA5 gene. In this study, we used systems genetic methods, statistical modeling, and immunostaining to identify and analyze candidate genes that modulate Hspa5 expression in the retina...
2016: Molecular Vision
https://www.readbyqxmd.com/read/27791469/new-anti-cancer-molecules-targeting-hspa5-bip-to-induce-endoplasmic-reticulum-stress-autophagy-and-apoptosis
#10
Michaël Cerezo, Stéphane Rocchi
Treatment of melanoma has significantly advanced over the last decade, with the development of targeted therapies against the MAPK pathway and immunotherapies to reactivate antitumor immunity. Unfortunately, currently more than 50% of patients are in treatment failure. Thus, identification of new common cellular vulnerability among melanoma cells is an urgent need and will help in the discovery of more efficient treatments against melanoma. We have focused our study on protein processing and have identified a new compound, HA15, targeting HSPA5/BiP, the master regulator of the unfolded protein response (UPR)...
January 2, 2017: Autophagy
https://www.readbyqxmd.com/read/27756316/integrins-are-not-essential-for-entry-of-coxsackievirus-a9-into-sw480-human-colon-adenocarcinoma-cells
#11
Outi Heikkilä, Pirjo Merilahti, Marika Hakanen, Eveliina Karelehto, Jonna Alanko, Maria Sukki, Saija Kiljunen, Petri Susi
BACKGROUND: Coxsackievirus A9 (CV-A9) is a pathogenic enterovirus type within the family Picornaviridae. CV-A9 infects A549 human epithelial lung carcinoma cells by attaching to the αVβ6 integrin receptor through a highly conserved Arg-Gly-Asp (RGD) motif, which is located at the exposed carboxy-terminus of the capsid protein VP1 detected in all studied clinical isolates. However, genetically-modified CV-A9 that lacks the RGD motif (CV-A9-RGDdel) has been shown to be infectious in some cell lines but not in A549, suggesting that RGD-mediated integrin binding is not always essential for efficient entry of CV-A9...
October 18, 2016: Virology Journal
https://www.readbyqxmd.com/read/27746171/characterization-of-cadmium-chloride-induced-bip-accumulation-in-xenopus-laevis-a6-kidney-epithelial-cells
#12
Cody S Shirriff, John J Heikkila
Endoplasmic reticulum (ER) stress can result in the accumulation of unfolded/misfolded protein in the ER lumen, which can trigger the unfolded protein response (UPR) resulting in the activation of various genes including immunoglobulin-binding protein (BiP; also known as glucose-regulated protein 78 or HSPA5). BiP, an ER heat shock protein 70 (HSP70) family member, binds to unfolded protein, inhibits their aggregation and re-folds them in an ATP-dependent manner. While cadmium, an environmental contaminant, was shown to induce the accumulation of HSP70 in vertebrate cells, less information is available regarding the effect of this metal on BiP accumulation or function...
January 2017: Comparative Biochemistry and Physiology. Toxicology & Pharmacology: CBP
https://www.readbyqxmd.com/read/27711126/integrated-left-ventricular-global-transcriptome-and-proteome-profiling-in-human-end-stage-dilated-cardiomyopathy
#13
Dilek Colak, Ayodele A Alaiya, Namik Kaya, Nzioka P Muiya, Olfat AlHarazi, Zakia Shinwari, Editha Andres, Nduna Dzimiri
AIMS: The disease pathways leading to idiopathic dilated cardiomyopathy (DCM) are still elusive. The present study investigated integrated global transcriptional and translational changes in human DCM for disease biomarker discovery. METHODS: We used identical myocardial tissues from five DCM hearts compared to five non-failing (NF) donor hearts for both transcriptome profiling using the ABI high-density oligonucleotide microarrays and proteome expression with One-Dimensional Nano Acquity liquid chromatography coupled with tandem mass spectrometry on the Synapt G2 system...
2016: PloS One
https://www.readbyqxmd.com/read/27684953/quantitative-proteomic-profiling-the-molecular-signatures-of-annexin-a5-in-lung-squamous-carcinoma-cells
#14
Bing Sun, Yuxin Bai, Liyuan Zhang, Linlin Gong, Xiaoyu Qi, Huizhen Li, Faming Wang, Xinming Chi, Yulin Jiang, Shujuan Shao
Lung cancer remains the leading cancer killer around the world. It's crucial to identify newer mechanism-based targets to effectively manage lung cancer. Annexin A5 (ANXA5) is a protein kinase C inhibitory protein and calcium dependent phospholipid-binding protein, which may act as an endogenous regulator of various pathophysiological processes. However, its molecular mechanism in lung cancer remains poorly understood. This study was designed to determine the mechanism of ANXA5 in lung cancer with a hope to obtain useful information to provide a new therapeutic target...
2016: PloS One
https://www.readbyqxmd.com/read/27663741/saliva-protein-biomarkers-to-detect-oral-squamous-cell-carcinoma-in-a-high-risk-population-in-taiwan
#15
Jau-Song Yu, Yi-Ting Chen, Wei-Fan Chiang, Yung-Chin Hsiao, Lichieh Julie Chu, Lai-Chu See, Chi-Sheng Wu, Hui-Tzu Tu, Hsiao-Wei Chen, Chia-Chun Chen, Wei-Chao Liao, Ya-Ting Chang, Chih-Ching Wu, Che-Yi Lin, Shyun-Yeu Liu, Shu-Ti Chiou, Shu-Li Chia, Kai-Ping Chang, Chih-Yen Chien, Su-Wei Chang, Chee-Jen Chang, John D Young, Chia C Pao, Yu-Sun Chang, Leland H Hartwell
Most cases of oral squamous cell carcinoma (OSCC) develop from visible oral potentially malignant disorders (OPMDs). The latter exhibit heterogeneous subtypes with different transformation potentials, complicating the early detection of OSCC during routine visual oral cancer screenings. To develop clinically applicable biomarkers, we collected saliva samples from 96 healthy controls, 103 low-risk OPMDs, 130 high-risk OPMDs, and 131 OSCC subjects. These individuals were enrolled in Taiwan's Oral Cancer Screening Program...
October 11, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27566407/proteomic-analysis-reveals-aberrant-expression-of-calr-and-hspa5-in-thyroid-tissues-of-graves-disease
#16
Shuai Meng, Wen Zhang, Li-Juan Guan, Fatuma-Said Muhali, Jiao-Zhen Zhou, Rong-Hua Song, Jian Xu, Jin-An Zhang
OBJECTIVES: To explore the proteomic changes in thyroid tissue from GD patients and find new biomarkers for the prevention, diagnosis as well as the treatment of GD. DESIGN AND METHODS: Group1 included five thyroid specimens of GD cases and 5 normal thyroid tissue samples which were removed surgically and collected. The proteins were extracted from these thyroid tissues and then the differentially expressed protein spots were identified by MALDI-TOF-MS. The interested proteins were further validated in more specimens (group2: 11 pathological thyroid specimens and 7 normal thyroid tissue samples)...
January 2017: Clinical Biochemistry
https://www.readbyqxmd.com/read/27560450/the-arginylation-branch-of-the-n-end-rule-pathway-positively-regulates-cellular-autophagic-flux-and-clearance-of-proteotoxic-proteins
#17
Yanxialei Jiang, Jeeyoung Lee, Jung Hoon Lee, Joon Won Lee, Ji Hyeon Kim, Won Hoon Choi, Young Dong Yoo, Hyunjoo Cha-Molstad, Bo Yeon Kim, Yong Tae Kwon, Sue Ah Noh, Kwang Pyo Kim, Min Jae Lee
The N-terminal amino acid of a protein is an essential determinant of ubiquitination and subsequent proteasomal degradation in the N-end rule pathway. Using para-chloroamphetamine (PCA), a specific inhibitor of the arginylation branch of the pathway (Arg/N-end rule pathway), we identified that blocking the Arg/N-end rule pathway significantly impaired the fusion of autophagosomes with lysosomes. Under ER stress, ATE1-encoded Arg-tRNA-protein transferases carry out the N-terminal arginylation of the ER heat shock protein HSPA5 that initially targets cargo proteins, along with SQSTM1, to the autophagosome...
November 2016: Autophagy
https://www.readbyqxmd.com/read/27420050/cellular-stress-and-p53-associated-apoptosis-by-juniperus-communis-l-berry-extract-treatment-in-the-human-sh-sy5y-neuroblastoma-cells
#18
Tiina A Lantto, Into Laakso, H J Damien Dorman, Timo Mauriala, Raimo Hiltunen, Sulev Kõks, Atso Raasmaja
Plant phenolics have shown to activate apoptotic cell death in different tumourigenic cell lines. In this study, we evaluated the effects of juniper berry extract (Juniperus communis L.) on p53 protein, gene expression and DNA fragmentation in human neuroblastoma SH-SY5Y cells. In addition, we analyzed the phenolic composition of the extract. We found that juniper berry extract activated cellular relocalization of p53 and DNA fragmentation-dependent cell death. Differentially expressed genes between treated and non-treated cells were evaluated with the cDNA-RDA (representational difference analysis) method at the early time point of apoptotic process when p53 started to be activated and no caspase activity was detected...
July 13, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27253232/molecular-mechanisms-of-toxicity-and-cell-damage-by-chemicals-in-a-human-pancreatic-beta-cell-line-1-1b4
#19
Srividya Vasu, Neville H McClenaghan, Peter R Flatt
OBJECTIVES: Mechanisms of toxicity and cell damage were investigated in novel clonal human pancreatic beta cell line, 1.1B4, after exposure to streptozotocin, alloxan, ninhydrin, and hydrogen peroxide. METHODS: Viability, DNA damage, insulin secretion/content, [Ca]i, and glucokinase/hexokinase, mRNA expression were measured by MTT assay, comet assay, radioimmunoassay, fluorometric imaging plate reader, enzyme-coupled photometry, and real-time polymerase chain reaction, respectively...
October 2016: Pancreas
https://www.readbyqxmd.com/read/27238082/compounds-triggering-er-stress-exert-anti-melanoma-effects-and-overcome-braf-inhibitor-resistance
#20
Michaël Cerezo, Abdelali Lehraiki, Antoine Millet, Florian Rouaud, Magali Plaisant, Emilie Jaune, Thomas Botton, Cyril Ronco, Patricia Abbe, Hella Amdouni, Thierry Passeron, Veronique Hofman, Baharia Mograbi, Anne-Sophie Dabert-Gay, Delphine Debayle, Damien Alcor, Nabil Rabhi, Jean-Sébastien Annicotte, Laurent Héliot, Mariano Gonzalez-Pisfil, Caroline Robert, Solange Moréra, Armelle Virougoux, Philippe Gual, Maruf M U Ali, Corine Bertolotto, Paul Hofman, Robert Ballotti, Rachid Benhida, Stéphane Rocchi
We have discovered and developed a series of molecules (thiazole benzenesulfonamides). HA15, the lead compound of this series, displayed anti-cancerous activity on all melanoma cells tested, including cells isolated from patients and cells that developed resistance to BRAF inhibitors. Our molecule displayed activity against other liquid and solid tumors. HA15 also exhibited strong efficacy in xenograft mouse models with melanoma cells either sensitive or resistant to BRAF inhibitors. Transcriptomic, proteomic, and biochemical studies identified the chaperone BiP/GRP78/HSPA5 as the specific target of HA15 and demonstrated that the interaction increases ER stress, leading to melanoma cell death by concomitant induction of autophagic and apoptotic mechanisms...
June 13, 2016: Cancer Cell
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