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coatomer protein

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https://www.readbyqxmd.com/read/28223711/identification-of-novel-cancer-therapeutic-targets-using-a-designed-and-pooled-shrna-library-screen
#1
David Oliver, Hao Ji, Piaomu Liu, Alexander Gasparian, Ellen Gardiner, Samuel Lee, Adrian Zenteno, Lillian O Perinskaya, Mengqian Chen, Phillip Buckhaults, Eugenia Broude, Michael D Wyatt, Homayoun Valafar, Edsel Peña, Michael Shtutman
Targeted cancer therapeutics aim to exploit tumor-specific, genetic vulnerabilities specifically affecting neoplastic cells without similarly affecting normal cells. Here we performed sequencing-based screening of an shRNA library on a panel of cancer cells of different origins as well as normal cells. The shRNA library was designed to target a subset of genes previously identified using a whole genome screening approach. This focused shRNA library was infected into cells followed by analysis of enrichment and depletion of the shRNAs over the course of cell proliferation...
February 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28126736/rna-editing-enzyme-adar2-is-a-mediator-of-neuropathic-pain-after-peripheral-nerve-injury
#2
Hitoshi Uchida, Shinji Matsumura, Shunpei Okada, Tsutomu Suzuki, Toshiaki Minami, Seiji Ito
Transcriptional and post-translational regulations are important in peripheral nerve injury-induced neuropathic pain, but little is known about the role of post-transcriptional modification. Our objective was to determine the possible effect of adenosine deaminase acting on RNA (ADAR) enzymes, which catalyze post-transcriptional RNA editing, in tactile allodynia, a hallmark of neuropathic pain. Seven days after L5 spinal nerve transection (SNT) in adult mice, we found an increase in ADAR2 expression and a decrease in ADAR3 expression in the injured, but not in the uninjured, dorsal root ganglions (DRGs)...
January 26, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28045387/crystal-structure-of-truncated-human-coatomer-protein-complex-subunit-%C3%AE-1-cop%C3%AE-1
#3
Sergey Lunev, Marije F W Semmelink, Jia Ling Xian, Kai Yu Ma, Anna J A Leenders, Alexander S S Dömling, Michael Shtutman, Matthew R Groves
The majority of modern anticancer approaches target DNA/protein targets involved in tumour-cell proliferation. Such approaches have a major drawback, as nonproliferating cancer cells remain unaffected and may cause relapse or remission. Human coatomer protein complex I (COPI) subunit ζ (Copζ), a component of the coat protein involved in cell apoptosis and intracellular trafficking, has recently been proposed as a potential anticancer drug target. Previous studies have shown that two different isoforms of the Copζ subunit exist in mammalian cells...
January 1, 2017: Acta Crystallographica. Section F, Structural Biology Communications
https://www.readbyqxmd.com/read/28041939/involvement-of-the-coatomer-protein-complex-i-in-the-intracellular-traffic-of-the-delta-opioid-receptor
#4
Étienne St-Louis, Jade Degrandmaison, Sébastien Grastilleur, Samuel Génier, Véronique Blais, Christine Lavoie, Jean-Luc Parent, Louis Gendron
The delta opioid receptor (DOPr) is known to be mainly expressed in intracellular compartments. It remains unknown why DOPr is barely exported to the cell surface, but it seems that a substantial proportion of the immature receptor is trapped within the endoplasmic reticulum (ER) and the Golgi network. In the present study, we performed LC-MS/MS analysis to identify putative protein partners involved in the retention of DOPr. Analysis of the proteins co-immunoprecipitating with Flag-DOPr in transfected HEK293 cells revealed the presence of numerous subunits of the coatomer protein complex I (COPI), a vesicle-coating complex involved in recycling resident proteins from the Golgi back to the ER...
December 30, 2016: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28025315/%C3%AE-2-cop-is-involved-in-early-secretory-traffic-in-arabidopsis-and-is-required-for-plant-growth
#5
Fátima Gimeno-Ferrer, Noelia Pastor-Cantizano, César Bernat-Silvestre, Pilar Selvi-Martínez, Francisco Vera-Sirera, Caiji Gao, Miguel Angel Perez-Amador, Liwen Jiang, Fernando Aniento, María Jesús Marcote
COP (coat protein) I-coated vesicles mediate intra-Golgi transport and retrograde transport from the Golgi to the endoplasmic reticulum. These vesicles form through the action of the small GTPase ADP-ribosylation factor 1 (ARF1) and the COPI heptameric protein complex (coatomer), which consists of seven subunits (α-, β-, β'-, γ-, δ-, ε- and ζ-COP). In contrast to mammals and yeast, several isoforms for coatomer subunits, with the exception of γ and δ, have been identified in Arabidopsis. To understand the role of COPI proteins in plant biology, we have identified and characterized a loss-of-function mutant of α2-COP, an Arabidopsis α-COP isoform...
December 26, 2016: Journal of Experimental Botany
https://www.readbyqxmd.com/read/28010187/components-of-the-snare-containing-regulon-are-co-regulated-in-root-cells-undergoing-defense
#6
Vincent P Klink, Keshav Sharma, Shankar R Pant, Brant McNeece, Prakash Niraula, Gary W Lawrence
The term regulon has been coined in the genetic model plant Arabidopsis thaliana, denoting a structural and physiological defense apparatus defined genetically through the identification of the penetration (pen) mutants. The regulon is composed partially by the soluble N-ethylmaleimide-sensitive fusion protein attachment protein receptor (SNARE) syntaxin PEN1. PEN1 has homology to a Saccharomyces cerevisae gene that regulates a Secretion (Sec) protein, Suppressor of Sec 1 (Sso1p). The regulon is also composed of the β-glucosidase (PEN2) and an ATP binding cassette (ABC) transporter (PEN3)...
December 23, 2016: Plant Signaling & Behavior
https://www.readbyqxmd.com/read/27986120/copb2-is-upregulated-in-prostate-cancer-and-regulates-pc-3-cell-proliferation-cell-cycle-and-apoptosis
#7
Yuanyuan Mi, Menglei Yu, Lifeng Zhang, Chuanyu Sun, Bingbing Wei, Weihong Ding, Yingfeng Zhu, Jianmin Tang, Guowei Xia, Lijie Zhu
BACKGROUND AND AIMS: Transport of membranes and proteins in eukaryotic cells is mediated by vesicular carriers. Coatomer complex I (COPI)-coated vesicles are involved in the transport between endoplasmic reticulum (ER) and Golgi complex. Several studies indicated that some subunits of COPI were correlated with the cell proliferation of malignant tumors. The present study focused on the function of coatomer protein complex subunit β 2 (COPB2), one of seven proteins in COPI, in prostate cancer (PCa)...
August 2016: Archives of Medical Research
https://www.readbyqxmd.com/read/27929413/exosome-proteome-of-u-87mg-glioblastoma-cells
#8
Sohyun Chun, Seunghyun Ahn, Chang-Hwan Yeom, Seyeon Park
Exosomes are small membrane vesicles between 30 and 100 nm in diameter secreted by many cell types, and are associated with a wide range of physiological and/or pathological processes. Exosomes containing proteins, lipids, mRNA, and microRNA contribute to cell-to-cell communication and cell-to-environment regulation, however, their biological functions are not yet fully understood. In this report, exosomes in the glioblastoma cell line, U-87MG, were isolated and the proteome was investigated. In addition, exosome proteome changes in U-87MG cells exposed to a low temperature were investigated to elucidate whether the exosome proteome could respond to an external stimulus...
December 6, 2016: Biology
https://www.readbyqxmd.com/read/27923433/circulating-anti-coatomer-protein-complex-subunit-epsilon-cope-autoantibodies-as-a-potential-biomarker-for-cardiovascular-and-cerebrovascular-events-in-patients-with-obstructive-sleep-apnea
#9
Takuma Matsumura, Jiro Terada, Taku Kinoshita, Yoriko Sakurai, Misuzu Yahaba, Ryogo Ema, Atsuko Amata, Seiichiro Sakao, Kengo Nagashima, Koichiro Tatsumi, Takaki Hiwasa
STUDY OBJECTIVES: Although moderate to severe obstructive sleep apnea (OSA) is an independent risk factor for severe arteriosclerotic diseases such as cardiovascular disease (CVD) and stroke, the development of atherosclerosis-related diseases cannot yet be predicted in OSA patients. In a pilot study, we identified autoantibodies against the coatomer protein complex, subunit epsilon [circulating anti-coatomer protein complex subunit epsilon autoantibody (COPE-Ab)], a cytosolic complex that mediates protein transport in the Golgi compartment, as a potential novel biomarker of atherosclerosis...
November 28, 2016: Journal of Clinical Sleep Medicine: JCSM: Official Publication of the American Academy of Sleep Medicine
https://www.readbyqxmd.com/read/27510922/autophagy-initiation-by-ulk-complex-assembly-on-er-tubulovesicular-regions-marked-by-atg9-vesicles
#10
Eleftherios Karanasios, Simon A Walker, Hanneke Okkenhaug, Maria Manifava, Eric Hummel, Hans Zimmermann, Qashif Ahmed, Marie-Charlotte Domart, Lucy Collinson, Nicholas T Ktistakis
Autophagosome formation requires sequential translocation of autophagy-specific proteins to membranes enriched in PI3P and connected to the ER. Preceding this, the earliest autophagy-specific structure forming de novo is a small punctum of the ULK1 complex. The provenance of this structure and its mode of formation are unknown. We show that the ULK1 structure emerges from regions, where ATG9 vesicles align with the ER and its formation requires ER exit and coatomer function. Super-resolution microscopy reveals that the ULK1 compartment consists of regularly assembled punctate elements that cluster in progressively larger spherical structures and associates uniquely with the early autophagy machinery...
August 11, 2016: Nature Communications
https://www.readbyqxmd.com/read/27476655/arcn1-mutations-cause-a-recognizable-craniofacial-syndrome-due-to-copi-mediated-transport-defects
#11
Kosuke Izumi, Maggie Brett, Eriko Nishi, Séverine Drunat, Ee-Shien Tan, Katsunori Fujiki, Sophie Lebon, Breana Cham, Koji Masuda, Michiko Arakawa, Adeline Jacquinet, Yusuke Yamazumi, Shu-Ting Chen, Alain Verloes, Yuki Okada, Yuki Katou, Tomohiko Nakamura, Tetsu Akiyama, Pierre Gressens, Roger Foo, Sandrine Passemard, Ene-Choo Tan, Vincent El Ghouzzi, Katsuhiko Shirahige
Cellular homeostasis is maintained by the highly organized cooperation of intracellular trafficking systems, including COPI, COPII, and clathrin complexes. COPI is a coatomer protein complex responsible for intracellular protein transport between the endoplasmic reticulum and the Golgi apparatus. The importance of such intracellular transport mechanisms is underscored by the various disorders, including skeletal disorders such as cranio-lenticulo-sutural dysplasia and osteogenesis imperfect, caused by mutations in the COPII coatomer complex...
August 4, 2016: American Journal of Human Genetics
https://www.readbyqxmd.com/read/27472951/structural-characterization-of-coatomer-in-its-cytosolic-state
#12
Shengliu Wang, Yujia Zhai, Xiaoyun Pang, Tongxin Niu, Yue-He Ding, Meng-Qiu Dong, Victor W Hsu, Zhe Sun, Fei Sun
Studies on coat protein I (COPI) have contributed to a basic understanding of how coat proteins generate vesicles to initiate intracellular transport. The core component of the COPI complex is coatomer, which is a multimeric complex that needs to be recruited from the cytosol to membrane in order to function in membrane bending and cargo sorting. Previous structural studies on the clathrin adaptors have found that membrane recruitment induces a large conformational change in promoting their role in cargo sorting...
August 2016: Protein & Cell
https://www.readbyqxmd.com/read/27413011/distinct-isoform-specific-complexes-of-tango1-cooperatively-facilitate-collagen-secretion-from-the-endoplasmic-reticulum
#13
Miharu Maeda, Kota Saito, Toshiaki Katada
Collagens synthesized within the endoplasmic reticulum (ER) are too large to fit in conventional COPII-coated transport vesicles; thus their export from the ER requires specialized factors. TANGO1 (L) is an integral membrane protein that binds to collagen and the coatomer of vesicles and is necessary for collagen secretion from the ER. Here we characterized the short isoform of TANGO1 (TANGO1S), lacking the collagen-binding domain, and found that it was independently required for collagen export from the ER...
September 1, 2016: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/27365400/discovery-proteomics-identifies-a-molecular-link-between-the-coatomer-protein-complex-i-and-androgen-receptor-dependent-transcription
#14
Jordy J Hsiao, Melinda M Smits, Brandon H Ng, Jinhee Lee, Michael E Wright
Aberrant androgen receptor (AR)-dependent transcription is a hallmark of human prostate cancers. At the molecular level, ligand-mediated AR activation is coordinated through spatial and temporal protein-protein interactions involving AR-interacting proteins, which we designate the "AR-interactome." Despite many years of research, the ligand-sensitive protein complexes involved in ligand-mediated AR activation in prostate tumor cells have not been clearly defined. Here, we describe the development, characterization, and utilization of a novel human LNCaP prostate tumor cell line, N-AR, which stably expresses wild-type AR tagged at its N terminus with the streptavidin-binding peptide epitope (streptavidin-binding peptide-tagged wild-type androgen receptor; SBP-AR)...
September 2, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27298352/%C3%AE-cop-contains-a-helix-c-terminal-to-its-longin-domain-key-to-copi-dynamics-and-function
#15
Eric C Arakel, Kora P Richter, Anne Clancy, Blanche Schwappach
Membrane recruitment of coatomer and formation of coat protein I (COPI)-coated vesicles is crucial to homeostasis in the early secretory pathway. The conformational dynamics of COPI during cargo capture and vesicle formation is incompletely understood. By scanning the length of δ-COP via functional complementation in yeast, we dissect the domains of the δ-COP subunit. We show that the μ-homology domain is dispensable for COPI function in the early secretory pathway, whereas the N-terminal longin domain is essential...
June 21, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27048656/copa-syndrome-a-novel-autosomal-dominant-immune-dysregulatory-disease
#16
EDITORIAL
Timothy J Vece, Levi B Watkin, Sarah K Nicholas, Debra Canter, Michael C Braun, Robert Paul Guillerman, Karen W Eldin, Grant Bertolet, Scott D McKinley, Marietta de Guzman, Lisa R 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/27039902/hypoxia-reduces-er-to-golgi-protein-trafficking-and-increases-cell-death-by-inhibiting-the-adaptive-unfolded-protein-response-in-mouse-beta-cells
#17
Mohammed Bensellam, Emma L Maxwell, Jeng Yie Chan, Jude Luzuriaga, Phillip K West, Jean-Christophe Jonas, Jenny E Gunton, D Ross Laybutt
AIMS/HYPOTHESIS: Hypoxia may contribute to beta cell failure in type 2 diabetes and islet transplantation. The adaptive unfolded protein response (UPR) is required for endoplasmic reticulum (ER) homeostasis. Here we investigated whether or not hypoxia regulates the UPR in beta cells and the role the adaptive UPR plays during hypoxic stress. METHODS: Mouse islets and MIN6 cells were exposed to various oxygen (O2) tensions. DNA-damage inducible transcript 3 (DDIT3), hypoxia-inducible transcription factor (HIF)1α and HSPA5 were knocked down using small interfering (si)RNA; Hspa5 was also overexpressed...
July 2016: Diabetologia
https://www.readbyqxmd.com/read/26999125/first-generation-antipsychotic-haloperidol-alters-the-functionality-of-the-late-endosomal-lysosomal-compartment-in-vitro
#18
Alberto Canfrán-Duque, Luis C Barrio, Milagros Lerma, Gema de la Peña, Jorge Serna, Oscar Pastor, Miguel A Lasunción, Rebeca Busto
First- and second-generation antipsychotics (FGAs and SGAs, respectively), have the ability to inhibit cholesterol biosynthesis and also to interrupt the intracellular cholesterol trafficking, interfering with low-density lipoprotein (LDL)-derived cholesterol egress from late endosomes/lysosomes. In the present work, we examined the effects of FGA haloperidol on the functionality of late endosomes/lysosomes in vitro. In HepG2 hepatocarcinoma cells incubated in the presence of 1,1'-dioctadecyl-3,3,3,3'-tetramethylindocarbocyanineperchlorate (DiI)-LDL, treatment with haloperidol caused the enlargement of organelles positive for late endosome markers lysosome-associated membrane protein 2 (LAMP-2) and LBPA (lysobisphosphatidic acid), which also showed increased content of both free-cholesterol and DiI derived from LDL...
March 18, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/26986486/%C3%AE-cop-as-a-component-of-transport-vesicles-for-hdl-apolipoprotein-mediated-cholesterol-exocytosis
#19
Weilie Ma, Margarita Lin, Hang Ding, Guorong Lin, Zhizhen Zhang
OBJECTIVE: HDL and its apolipoproteins protect against atherosclerotic disease partly by removing excess cholesterol from macrophage foam cells. But the underlying mechanisms of cholesterol clearance are still not well defined. We investigated roles of vesicle trafficking of coatomer β-COP in delivering cholesterol to the cell surface during apoA-1 and apoE-mediated lipid efflux from fibroblasts and THP-1 macrophages. METHODS: shRNA knockout, confocal and electron microscopy and biochemical analysis were used to investigate the roles of β-COP in apolipoprotein-mediated cholesterol efflux in fibroblasts and THP-1 macrophages...
2016: PloS One
https://www.readbyqxmd.com/read/26968245/change-of-uterine-histroph-proteins-during-follicular-and-luteal-phase-in-pigs
#20
Sang-Hee Lee, Eun-Ji Song, Yong Hwangbo, Seunghyung Lee, Choon-Keun Park
The aim of this study was to examine protein expression patterns of uterine histroph (UH) during the follicular phase (FP) and luteal phase (LP) in pigs. Forty-nine common proteins were identified from FP and LP samples; five were significantly down-regulated (>1.5-fold), while 15 were significantly up-regulated (>1.5-fold) in LPUH compared with FPUH (P<0.05). The 20 differentially-expressed proteins are involved in cell proliferation, cell responses, translation, transport, and metabolism and their molecular functions include nucleic acid binding, oxygen activity, enzymatic activity, growth activity, iron binding, and redox binding...
May 2016: Animal Reproduction Science
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