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Copa mutations

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https://www.readbyqxmd.com/read/29196126/oncogenic-kit-signalling-on-the-golgi-is-suppressed-by-blocking-secretory-trafficking-with-m-copa-in-gastrointestinal-stromal-tumours
#1
Yuuki Obata, Keita Horikawa, Isamu Shiina, Tsuyoshi Takahashi, Takatsugu Murata, Yasutaka Tasaki, Kyohei Suzuki, Keita Yonekura, Hiroyasu Esumi, Toshirou Nishida, Ryo Abe
Most gastrointestinal stromal tumours (GISTs) are caused by constitutively active mutations in Kit tyrosine kinase. The drug imatinib, a specific Kit inhibitor, improves the prognosis of metastatic GIST patients, but these patients become resistant to the drug by acquiring secondary mutations in the Kit kinase domain. We recently reported that a Kit mutant causes oncogenic signals only on the Golgi apparatus in GISTs. In this study, we show that in GIST, 2-methylcoprophilinamide (M-COPA, also known as "AMF-26"), an inhibitor of biosynthetic protein trafficking from the endoplasmic reticulum (ER) to the Golgi, suppresses Kit autophosphorylation at Y703/Y721/Y730/Y936, resulting in blockade of oncogenic signalling...
November 28, 2017: Cancer Letters
https://www.readbyqxmd.com/read/29137621/copa-syndrome-in-an-icelandic-family-caused-by-a-recurrent-missense-mutation-in-copa
#2
Brynjar O Jensson, Sif Hansdottir, Gudny A Arnadottir, Gerald Sulem, Ragnar P Kristjansson, Asmundur Oddsson, Stefania Benonisdottir, Hakon Jonsson, Agnar Helgason, Jona Saemundsdottir, Olafur T Magnusson, Gisli Masson, Gudmundur A Thorisson, Adalbjorg Jonasdottir, Aslaug Jonasdottir, Asgeir Sigurdsson, Ingileif Jonsdottir, Vigdis Petursdottir, Jon R Kristinsson, Daniel F Gudbjartsson, Unnur Thorsteinsdottir, Reynir Arngrimsson, Patrick Sulem, Gunnar Gudmundsson, Kari Stefansson
BACKGROUND: Rare missense mutations in the gene encoding coatomer subunit alpha (COPA) have recently been shown to cause autoimmune interstitial lung, joint and kidney disease, also known as COPA syndrome, under a dominant mode of inheritance. CASE PRESENTATION: Here we describe an Icelandic family with three affected individuals over two generations with a rare clinical presentation of lung and joint disease and a histological diagnosis of follicular bronchiolitis...
November 14, 2017: BMC Medical Genetics
https://www.readbyqxmd.com/read/29030294/type-i-interferon-pathway-activation-in-copa-syndrome
#3
Stefano Volpi, Jessica Tsui, Marcello Mariani, Claudia Pastorino, Roberta Caorsi, Oliviero Sacco, Angelo Ravelli, Anthony K Shum, Marco Gattorno, Paolo Picco
Mutations of the COPA gene cause an immune dysregulatory disease characterised by polyarticular arthritis and progressive interstitial lung disease with pulmonary haemorrhages. We report the case of a young girl that presented at age 3 with polyarticular arthritis, chronic cough and high titer rheumatoid factor. Radiologic imaging showed interstitial lung disease with tree-in-a-bud nodules and air-filled cysts. Targeted genetic analysis of COPA gene showed the reported c.698G>A mutation. The patient was lost to follow up for 3years during which therapy was discontinued with the development of joint damage and deformities...
October 10, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28904385/rapid-discovery-of-de-novo-deleterious-mutations-in-cattle-enhances-the-value-of-livestock-as-model-species
#4
E Bourneuf, P Otz, H Pausch, V Jagannathan, P Michot, C Grohs, G Piton, S Ammermüller, M-C Deloche, S Fritz, H Leclerc, C Péchoux, A Boukadiri, C Hozé, R Saintilan, F Créchet, M Mosca, D Segelke, F Guillaume, S Bouet, A Baur, A Vasilescu, L Genestout, A Thomas, A Allais-Bonnet, D Rocha, M-A Colle, C Klopp, D Esquerré, C Wurmser, K Flisikowski, H Schwarzenbacher, J Burgstaller, M Brügmann, E Dietschi, N Rudolph, M Freick, S Barbey, G Fayolle, C Danchin-Burge, L Schibler, B Bed'Hom, B J Hayes, H D Daetwyler, R Fries, D Boichard, D Pin, C Drögemüller, A Capitan
In humans, the clinical and molecular characterization of sporadic syndromes is often hindered by the small number of patients and the difficulty in developing animal models for severe dominant conditions. Here we show that the availability of large data sets of whole-genome sequences, high-density SNP chip genotypes and extensive recording of phenotype offers an unprecedented opportunity to quickly dissect the genetic architecture of severe dominant conditions in livestock. We report on the identification of seven dominant de novo mutations in CHD7, COL1A1, COL2A1, COPA, and MITF and exploit the structure of cattle populations to describe their clinical consequences and map modifier loci...
September 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28403213/m-copa-suppresses-endolysosomal-kit-akt-oncogenic-signalling-through-inhibiting-the-secretory-pathway-in-neoplastic-mast-cells
#5
Yasushi Hara, Yuuki Obata, Keita Horikawa, Yasutaka Tasaki, Kyohei Suzuki, Takatsugu Murata, Isamu Shiina, Ryo Abe
Gain-of-function mutations in Kit receptor tyrosine kinase result in the development of a variety of cancers, such as mast cell tumours, gastrointestinal stromal tumours (GISTs), acute myeloid leukemia, and melanomas. The drug imatinib, a selective inhibitor of Kit, is used for treatment of mutant Kit-positive cancers. However, mutations in the Kit kinase domain, which are frequently found in neoplastic mast cells, confer an imatinib resistance, and cancers expressing the mutants can proliferate in the presence of imatinib...
2017: PloS One
https://www.readbyqxmd.com/read/28293558/the-copper-efflux-regulator-cuer-is-subject-to-atp-dependent-proteolysis-in-escherichia-coli
#6
Lisa-Marie Bittner, Alexander Kraus, Sina Schäkermann, Franz Narberhaus
The trace element copper serves as cofactor for many enzymes but is toxic at elevated concentrations. In bacteria, the intracellular copper level is maintained by copper efflux systems including the Cue system controlled by the transcription factor CueR. CueR, a member of the MerR family, forms homodimers, and binds monovalent copper ions with high affinity. It activates transcription of the copper tolerance genes copA and cueO via a conserved DNA-distortion mechanism. The mechanism how CueR-induced transcription is turned off is not fully understood...
2017: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/27862834/transcriptional-response-of-erwinia-amylovora-upon-copper-shock-in-vivo-role-of-the-copa-gene
#7
Begoña Águila-Clares, Luisa F Castiblanco, José Manuel Quesada, Ramón Penyalver, Juan Carbonell, María M López, Ester Marco-Noales, George W Sundin
Fire blight is a devastating plant disease caused by the bacterium Erwinia amylovora and its control frequently is based on the use of copper-based compounds, for which the mechanisms of action are not well known. Consequently, here we investigate the response of E. amylovora to copper shock by a whole genome microarray approach. Transcriptional analyses showed that, in the presence of copper, 23 genes were increased in expression; these genes were classified mainly into the transport and stress functional categories...
November 14, 2016: Molecular Plant Pathology
https://www.readbyqxmd.com/read/27642173/using-rna-seq-snp-data-to-reveal-potential-causal-mutations-related-to-pig-production-traits-and-rna-editing
#8
A M Martínez-Montes, A Fernández, D Pérez-Montarelo, E Alves, R M Benítez, Y Nuñez, C Óvilo, N Ibañez-Escriche, J M Folch, A I Fernández
RNA-Seq technology is widely used in quantitative gene expression studies and identification of non-annotated transcripts. However this technology also can be used for polymorphism detection and RNA editing in transcribed regions in an efficient and cost-effective way. This study used SNP data from an RNA-Seq assay to identify genes and mutations underlying production trait variations in an experimental pig population. The hypothalamic and hepatic transcriptomes of nine extreme animals for growth and fatness from an (Iberian × Landrace) × Landrace backcross were analyzed by RNA-Seq methodology, and SNP calling was conducted...
April 2017: Animal Genetics
https://www.readbyqxmd.com/read/27436848/prognostic-role-of-tumor-pik3ca-mutation-in-colorectal-cancer-a-systematic-review-and-meta-analysis
#9
REVIEW
Z B Mei, C Y Duan, C B Li, L Cui, S Ogino
BACKGROUND: Somatic mutations in the phosphatidylinositol-4,5-bisphosphate 3-kinase/AKT pathway play a vital role in carcinogenesis. Approximately 15%-20% of colorectal cancers (CRCs) harbor activating mutations in PIK3CA, making it one of the most frequently mutated genes in CRC. We thus carried out a systematic review and meta-analysis investigating the prognostic significance of PIK3CA mutations in CRC. MATERIALS AND METHODS: Electronic databases were searched from inception through May 2015...
October 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/27402006/virological-efficacy-of-pi-monotherapy-for-hiv-1-in-clinical-practice
#10
Kate El Bouzidi, Dami Collier, Eleni Nastouli, Andrew J Copas, Robert F Miller, Ravindra K Gupta
BACKGROUND: Clinical trials of PI monotherapy indicate that most participants maintain viral suppression and emergent protease resistance is rare. However, outcomes among patients receiving PI monotherapy for clinical reasons, such as toxicity or adherence issues, are less well studied. METHODS: An observational study of patients attending an HIV treatment centre in London, UK, who had received PI monotherapy between 2004 and 2013, was conducted using prospectively collected clinical data and genotypic resistance reports...
November 2016: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/27048656/copa-syndrome-a-novel-autosomal-dominant-immune-dysregulatory-disease
#11
REVIEW
Timothy J Vece, Levi B Watkin, Sarah Nicholas, Debra Canter, Michael C Braun, R Paul Guillerman, Karen W Eldin, Grant Bertolet, Scott McKinley, Marietta de Guzman, Lisa Forbes, Ivan Chinn, Jordan S Orange
Inherently defective immunity typically results in either ineffective host defense, immune regulation, or both. As a category of primary immunodeficiency diseases, those that impair immune regulation can lead to autoimmunity and/or autoinflammation. In this review we focus on one of the most recently discovered primary immunodeficiencies that leads to immune dysregulation: "Copa syndrome". Copa syndrome is named for the gene mutated in the disease, which encodes the alpha subunit of the coatomer complex-I that, in aggregate, is devoted to transiting molecular cargo from the Golgi complex to the endoplasmic reticulum (ER)...
May 2016: Journal of Clinical Immunology
https://www.readbyqxmd.com/read/26929132/dissection-of-the-sensor-domain-of-the-copper-responsive-histidine-kinase-cors-from-myxococcus-xanthus
#12
María Celestina Sánchez-Sutil, Francisco Javier Marcos-Torres, Juana Pérez, María Ruiz-González, Elena García-Bravo, Marina Martínez-Cayuela, Nuria Gómez-Santos, Aurelio Moraleda-Muñoz, José Muñoz-Dorado
Myxococcus xanthus CorSR is a two-component system responsible for maintaining the response of this bacterium to copper. In the presence of this metal it upregulates, among others, the genes encoding the multicopper oxidase CuoA and the P1B -ATPase CopA. Dissection of the periplasmic sensor domain of the histidine kinase CorS by the analysis of a series of in-frame deletion mutants generated in this portion of the protein has revealed that copper sensing requires a region of 28 residues in the N terminus and another region of nine residues in the C terminus...
June 2016: Environmental Microbiology Reports
https://www.readbyqxmd.com/read/26262888/novel-monogenic-diseases-causing-human-autoimmunity
#13
REVIEW
Isabelle Melki, Yanick J Crow
Fuelled by the on-going sequencing revolution, the last two years have seen a number of exciting discoveries relating to monogenic disorders predisposing to autoimmunity that provide new insights into the function of the human immune system. Here we discuss a selection of these diseases due to mutations in PRKCD, CTLA4, STAT3, IFIH1, TMEM173 and COPA.
December 2015: Current Opinion in Immunology
https://www.readbyqxmd.com/read/26196376/newly-recognized-mendelian-disorders-with-rheumatic-manifestations
#14
REVIEW
Adriana Almeida de Jesus, Raphaela Goldbach-Mansky
PURPOSE OF REVIEW: We review newly discovered monogenic immune-dysregulatory disorders that were reported in Pubmed over the last year. RECENT FINDINGS: Fourteen novel monogenic immune-dysregulatory disorders that present with innate and acquired/adaptive immune dysregulation and inflammatory clinical phenotypes were identified. These include autosomal-dominant gain-of function mutations in viral innate immune sensors or their adaptors, TMEM173/STING IFIH1/MDA5 and DDX58/RIG-I that cause complex clinical syndromes distinct from IL-1-mediated diseases and present with a chronic type I interferon (IFN Type I) signature in peripheral blood...
September 2015: Current Opinion in Rheumatology
https://www.readbyqxmd.com/read/26042826/dominant-red-coat-color-in-holstein-cattle-is-associated-with-a-missense-mutation-in-the-coatomer-protein-complex-subunit-alpha-copa-gene
#15
Ben Dorshorst, Corneliu Henegar, Xiaoping Liao, Markus Sällman Almén, Carl-Johan Rubin, Shosuke Ito, Kazumasa Wakamatsu, Paul Stothard, Brian Van Doormaal, Graham Plastow, Gregory S Barsh, Leif Andersson
Coat color in Holstein dairy cattle is primarily controlled by the melanocortin 1 receptor (MC1R) gene, a central determinant of black (eumelanin) vs. red/brown pheomelanin synthesis across animal species. The major MC1R alleles in Holsteins are Dominant Black (MC1RD) and Recessive Red (MC1Re). A novel form of dominant red coat color was first observed in an animal born in 1980. The mutation underlying this phenotype was named Dominant Red and is epistatic to the constitutively activated MC1RD. Here we show that a missense mutation in the coatomer protein complex, subunit alpha (COPA), a gene with previously no known role in pigmentation synthesis, is completely associated with Dominant Red in Holstein dairy cattle...
2015: PloS One
https://www.readbyqxmd.com/read/26013484/the-copyaz-operon-functions-in-copper-efflux-biofilm-formation-genetic-transformation-and-stress-tolerance-in-streptococcus-mutans
#16
Kamna Singh, Dilani B Senadheera, Céline M Lévesque, Dennis G Cvitkovitch
UNLABELLED: In bacteria, copper homeostasis is closely monitored to ensure proper cellular functions while avoiding cell damage. Most Gram-positive bacteria utilize the copYABZ operon for copper homeostasis, where copA and copB encode copper-transporting P-type ATPases, whereas copY and copZ regulate the expression of the cop operon. Streptococcus mutans is a biofilm-forming oral pathogen that harbors a putative copper-transporting copYAZ operon. Here, we characterized the role of copYAZ operon in the physiology of S...
August 1, 2015: Journal of Bacteriology
https://www.readbyqxmd.com/read/25894502/copa-mutations-impair-er-golgi-transport-and-cause-hereditary-autoimmune-mediated-lung-disease-and-arthritis
#17
Levi B Watkin, Birthe Jessen, Wojciech Wiszniewski, Timothy J Vece, Max Jan, Youbao Sha, Maike Thamsen, Regie L P Santos-Cortez, Kwanghyuk Lee, Tomasz Gambin, Lisa R Forbes, Christopher S Law, Asbjørg Stray-Pedersen, Mickie H Cheng, Emily M Mace, Mark S Anderson, Dongfang Liu, Ling Fung Tang, Sarah K Nicholas, Karen Nahmod, George Makedonas, Debra L Canter, Pui-Yan Kwok, John Hicks, Kirk D Jones, Samantha Penney, Shalini N Jhangiani, Michael D Rosenblum, Sharon D Dell, Michael R Waterfield, Feroz R Papa, Donna M Muzny, Noah Zaitlen, Suzanne M Leal, Claudia Gonzaga-Jauregui, Eric Boerwinkle, N Tony Eissa, Richard A Gibbs, James R Lupski, Jordan S Orange, Anthony K Shum
Unbiased genetic studies have uncovered surprising molecular mechanisms in human cellular immunity and autoimmunity. We performed whole-exome sequencing and targeted sequencing in five families with an apparent mendelian syndrome of autoimmunity characterized by high-titer autoantibodies, inflammatory arthritis and interstitial lung disease. We identified four unique deleterious variants in the COPA gene (encoding coatomer subunit α) affecting the same functional domain. Hypothesizing that mutant COPA leads to defective intracellular transport via coat protein complex I (COPI), we show that COPA variants impair binding to proteins targeted for retrograde Golgi-to-ER transport...
June 2015: Nature Genetics
https://www.readbyqxmd.com/read/25547901/should-tyrosine-kinase-inhibitors-be-considered-for-advanced-non-small-cell-lung-cancer-patients-with-wild-type-egfr-two-systematic-reviews-and-meta-analyses-of-randomized-trials
#18
REVIEW
Claire L Vale, Sarah Burdett, David J Fisher, Neal Navani, Mahesh K B Parmar, Andrew J Copas, Jayne F Tierney
Guidance concerning tyrosine kinase inhibitors (TKIs) for patients with wild type epidermal growth factor receptor (EGFR) and advanced non-small-cell lung cancer (NSCLC) after first-line treatment is unclear. We assessed the effect of TKIs as second-line therapy and maintenance therapy after first-line chemotherapy in two systematic reviews and meta-analyses, focusing on patients without EGFR mutations. Systematic searches were completed and data extracted from eligible randomized controlled trials. Three analytical approaches were used to maximize available data...
May 2015: Clinical Lung Cancer
https://www.readbyqxmd.com/read/25092032/role-of-an-archaeal-pita-transporter-in-the-copper-and-arsenic-resistance-of-metallosphaera-sedula-an-extreme-thermoacidophile
#19
Samuel McCarthy, Chenbing Ai, Garrett Wheaton, Rahul Tevatia, Valerie Eckrich, Robert Kelly, Paul Blum
Thermoacidophilic archaea, such as Metallosphaera sedula, are lithoautotrophs that occupy metal-rich environments. In previous studies, an M. sedula mutant lacking the primary copper efflux transporter, CopA, became copper sensitive. In contrast, the basis for supranormal copper resistance remained unclear in the spontaneous M. sedula mutant, CuR1. Here, transcriptomic analysis of copper-shocked cultures indicated that CuR1 had a unique regulatory response to metal challenge corresponding to the upregulation of 55 genes...
October 2014: Journal of Bacteriology
https://www.readbyqxmd.com/read/25030084/a-copper-responsive-gene-cluster-is-required-for-copper-homeostasis-and-contributes-to-oxidative-resistance-in-deinococcus-radiodurans-r1
#20
Zhongchao Zhao, Zhengfu Zhou, Liang Li, Xianyi Xian, Xiubin Ke, Ming Chen, Yuxiu Zhang
Excess copper is toxic to organisms, and therefore, copper homeostasis is important for the limitation of its cellular levels. However, copper homeostasis has not been studied to date in the bacteria Deinococcus radiodurans R1, which exhibits extreme resistance to various environmental stresses. We have identified a copper-responsive gene cluster that encodes CopA, which is a copper-transporting P1-type ATPase, CopZ, which is a copper metallochaperone, and CsoR, which is a copper-sensing repressor. Copper induces the transcription of genes in this cluster...
October 2014: Molecular BioSystems
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