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Adaptor protein 1

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https://www.readbyqxmd.com/read/27909244/cd4-down-regulation-by-hiv-1-nef-reveals-distinct-roles-for-%C3%AE-1-and-%C3%AE-2-subunits-of-ap-1-complex-in-protein-trafficking
#1
Lucas A Tavares, Eulália M L da Silva, Mara E da Silva-Januário, Yunan C Januário, Julianne V de Cavalho, Érika S Czernisz, Gonzalo A Mardones, Luis L P daSilva
The HIV accessory protein Nef is a major determinant of viral pathogenesis that facilitates viral particle release, prevents viral antigen presentation and increases infectivity of new virus particles. These functions of Nef involve its ability to remove specific host proteins from the surface of infected cells, including the CD4 receptor. Nef binds to the adaptor protein 2 (AP-2) and CD4 in clathrin-coated pits, forcing CD4 internalization and subsequent target to lysosomes. Herein, we report that this lysosomal targeting requires a variant of the AP-1 comprising the isoform 2 of γ-adaptin...
December 1, 2016: Journal of Cell Science
https://www.readbyqxmd.com/read/27893701/the-signaling-adaptor-traf1-negatively-regulates-toll-like-receptor-signaling-and-this-underlies-its-role-in-rheumatic-disease
#2
Ali A Abdul-Sater, Maria I Edilova, Derek L Clouthier, Achire Mbanwi, Elisabeth Kremmer, Tania H Watts
TRAF1 is a signaling adaptor known for its role in tumor necrosis factor receptor-induced cell survival. Here we show that monocytes from healthy human subjects with a rheumatoid arthritis-associated single-nucleotide polymorphism (SNP) in the TRAF1 gene express less TRAF1 protein but greater amounts of inflammatory cytokines in response to lipopolysaccharide (LPS). The TRAF1 MATH domain binds directly to three components of the linear ubiquitination (LUBAC) complex, SHARPIN, HOIP and HOIL-1, to interfere with the recruitment and linear ubiquitination of NEMO...
November 28, 2016: Nature Immunology
https://www.readbyqxmd.com/read/27889498/bloc-2-subunit-hps6-deficiency-affects-the-tubulation-and-secretion-of-von-willebrand-factor-from-mouse-endothelial-cells
#3
Jing Ma, Zhe Zhang, Lin Yang, Janos Kriston-Vizi, Daniel F Cutler, Wei Li
Hermansky-Pudlak syndrome (HPS) is a recessive disorder with bleeding diathesis, which has been linked to platelet granule defects. Both platelet granules and endothelial Weibel-Palade bodies (WPBs) are members of lysosome-related organelles (LROs) whose formation is regulated by HPS protein associated complexes such as BLOC (biogenesis of lysosome organelles complex) -1, -2, -3, AP-3 (adaptor protein complex-3) and HOPS (homotypic fusion and protein sorting complex). Von Willebrand factor (VWF) is critical to hemostasis, which is stored in a highly-multimerized form as tubules in the WPBs...
October 21, 2016: Journal of Genetics and Genomics, Yi Chuan Xue Bao
https://www.readbyqxmd.com/read/27889060/autosomal-recessive-mutations-in-ap3b2-adaptor-related-protein-complex-3-beta-2-subunit-cause-an-early-onset-epileptic-encephalopathy-with-optic-atrophy
#4
Mirna Assoum, Christophe Philippe, Bertrand Isidor, Laurence Perrin, Periklis Makrythanasis, Neal Sondheimer, Caroline Paris, Jessica Douglas, Gaetan Lesca, Stylianos Antonarakis, Hanan Hamamy, Thibaud Jouan, Yannis Duffourd, Stéphane Auvin, Aline Saunier, Amber Begtrup, Catherine Nowak, Nicolas Chatron, Dorothée Ville, Kamiar Mireskandari, Paolo Milani, Philippe Jonveaux, Guylène Lemeur, Mathieu Milh, Masano Amamoto, Mitsuhiro Kato, Mitsuko Nakashima, Noriko Miyake, Naomichi Matsumoto, Amira Masri, Christel Thauvin-Robinet, Jean-Baptiste Rivière, Laurence Faivre, Julien Thevenon
Early-onset epileptic encephalopathy (EOEE) represents a heterogeneous group of severe disorders characterized by seizures, interictal epileptiform activity with a disorganized electroencephalography background, developmental regression or retardation, and onset before 1 year of age. Among a cohort of 57 individuals with epileptic encephalopathy, we ascertained two unrelated affected individuals with EOEE associated with developmental impairment and autosomal-recessive variants in AP3B2 by means of whole-exome sequencing...
November 16, 2016: American Journal of Human Genetics
https://www.readbyqxmd.com/read/27883876/comprehensive-genomic-profiling-of-central-giant-cell-lesions-identifies-clinically-relevant-genomic-alterations
#5
Brett Bezak, Heidi Lehrke, Julia Elvin, Laurie Gay, David Schembri-Wismayer, Christopher Viozzi
PURPOSE: Comprehensive genomic profiling (CGP) can simultaneously detect clinically relevant genomic alterations (CRGAs) in hundreds of cancer-related genes and direct treatment toward patient-specific therapy options for many tumors. This pilot study aimed to use CGP to describe CRGAs present in central giant cell lesions (CGCLs) to characterize any possible underlying genomic drivers of CGCLs. MATERIALS AND METHODS: With institutional review board approval, electronic medical records were searched for patients with histologically confirmed CGCLs who underwent biopsy at Mayo Clinic from 2000 through 2014...
November 1, 2016: Journal of Oral and Maxillofacial Surgery
https://www.readbyqxmd.com/read/27876844/the-n-terminal-loop-of-irak-4-death-domain-regulates-ordered-assembly-of-the-myddosome-signalling-scaffold
#6
Anthony C G Dossang, Precious G Motshwene, Yang Yang, Martyn F Symmons, Clare E Bryant, Satty Borman, Julie George, Alexander N R Weber, Nicholas J Gay
Activation of Toll-like receptors induces dimerization and the recruitment of the death domain (DD) adaptor protein MyD88 into an oligomeric post receptor complex termed the Myddosome. The Myddosome is a hub for inflammatory and oncogenic signaling and has a hierarchical arrangement with 6-8 MyD88 molecules assembling with exactly 4 of IRAK-4 and 4 of IRAK-2. Here we show that a conserved motif in IRAK-4 (Ser8-X-X-X-Arg12) is autophosphorylated and that the phosphorylated DD is unable to form Myddosomes. Furthermore a mutant DD with the phospho-mimetic residue Asp at this position is impaired in both signalling and Myddosome assembly...
November 23, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27864235/l5-ldl-from-st-elevation-myocardial-infarction-patients-induces-il-1%C3%AE-production-via-lox-1-and-nlrp3-inflammasome-activation-in-macrophages
#7
Tzu-Ching Yang, Po-Yuan Chang, Shao-Chun Lu
L5-LDL, the most electronegative LDL associated with major cardiovascular risks, significantly rises in patients with ST-segment elevation myocardial infarction (STEMI). The inflammatory nature of atherosclerotic vascular diseases has prompted us to investigate whether L5-LDL induces the production of inflammatory cytokines, especially vascular ischemia-related interleukin (IL)-1β in the pathogenesis of STEMI. Clinical data showed that plasma levels of L5-LDL and IL-1β were higher in the STEMI patients than in the controls (p < 0...
November 18, 2016: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/27863839/antihyperuricemic-effect-of-liquiritigenin-in-potassium-oxonate-induced-hyperuricemic-rats
#8
Long Hongyan, Wu Suling, Zhu Weina, Zhang Yajie, Ruan Jie
The aim is to investigate the anti-hyperuricemic and renal protective effects of liquiritigenin in potassium oxonate-induced hyperuricemic rats. Hyperuricemia in rats was induced were induced with potassium oxonate (250mg/kg) intragastrically for 7 days, and liquiritigenin (20, 40mg/kg) and allopurinol (5mg/kg) were daily administrated to the rats orally 1h after the potassium oxonate exposure. Liquiritigenin significantly reversed the elevated productions of uric acid in serum and urine and pro-inflammation cytokines in serum and kidney, which shown that liquiritigenin has renal protective effects...
November 15, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27863378/aberrant-localization-of-apoptosis-protease-activating-factor-1-in-lipid-raft-sub-domains-of-diffuse-large-b-cell-lymphomas
#9
Jayshree L Hirpara, Thomas Loh, Siok Bian Ng, Wee Joo Chng, Shazib Pervaiz
Resistance to chemotherapy remains a challenge in the clinical management of diffuse B cell lymphomas despite aggressive chemotherapy such as CHOP and monoclonal CD20. Here we provide evidence that the apoptosome adaptor protein, Apaf-1, is mislocalized in primary cells derived from patients with diffuse large B cell lymphomas (DLBCL). Whereas, the total expression of Apaf-1 did not change, its sub-cellular localization was significantly different in DLBCL, compared to T cell lymphomas as well as cells derived from reactive lymphadenopathy biopsies...
November 14, 2016: Oncotarget
https://www.readbyqxmd.com/read/27852860/nes-masking-regulates-hiv-1-rev-trafficking-and-viral-rna-nuclear-export
#10
Ryan T Behrens, Mounavya Aligeti, Ginger M Pocock, Christina A Higgins, Nathan M Sherer
: HIV-1's Rev protein forms a homooligomeric adaptor complex linking viral RNAs to the cellular CRM1/Ran-GTP nuclear export machinery through the activity of Rev's prototypical leucine-rich nuclear export signal (NES). In this study we used a functional fluorescently-tagged Rev fusion protein as a platform to study the effects of modulating Rev NES identity, number, position, or strength on Rev subcellular trafficking, viral RNA nuclear export, and infectious virion production. We found Rev activity to be remarkably tolerant of diverse NES sequences including supraphysiological NES (SNES) peptides that otherwise arrest CRM1 transport complexes at nuclear pores...
November 16, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27835873/proteomic-identification-of-the-oncoprotein-stat3-as-a-target-of-a-novel-skp1-inhibitor
#11
Xin Cheng, Yong-Qiang Liu, Gui-Zhen Wang, Li-Na Yang, Yong-Zhi Lu, Xin-Chun Li, Bo Zhou, Li-Wei Qu, Xiao-Lu Wang, Yong-Xian Cheng, Jinsong Liu, Sheng-Ce Tao, Guang-Biao Zhou
The S phase kinase-associated protein 1 (Skp1), an adaptor protein of the Skp1-Cul1-F-box protein complex, binds the ubiquitin E3 ligase Skp2 and is critical to its biological functions. Targeting of Skp1 by a small compound 6-O-angeloylplenolin (6-OAP) results in dissociation and degradation of Skp2 and mitotic arrest of lung cancer cells. Here, by using a proteome microarray containing 16,368 proteins and a biotinylated 6-OAP, we identified 99 proteins that could bind 6-OAP, with Skp1 and STAT3 sitting at the central position of the 6-OAP interactome...
November 7, 2016: Oncotarget
https://www.readbyqxmd.com/read/27833610/tcr-triggering-induces-the-formation-of-lck-rack1-actinin-1-multiprotein-network-affecting-lck-redistribution
#12
Ondřej Ballek, Jan Valečka, Martina Dobešová, Adéla Broučková, Jasper Manning, Pavel Řehulka, Jiří Stulík, Dominik Filipp
The initiation of T-cell signaling is critically dependent on the function of the member of Src family tyrosine kinases, Lck. Upon T-cell antigen receptor (TCR) triggering, Lck kinase activity induces the nucleation of signal-transducing hubs that regulate the formation of complex signaling network and cytoskeletal rearrangement. In addition, the delivery of Lck function requires rapid and targeted membrane redistribution, but the mechanism underpinning this process is largely unknown. To gain insight into this process, we considered previously described proteins that could assist in this process via their capacity to interact with kinases and regulate their intracellular translocations...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27823962/the-transient-receptor-potential-ankyrin-1-mediates-mechanical-hyperalgesia-induced-by-the-activation-of-b1-receptor-in-mice
#13
Flavia Carla Meotti, Cláudia Pinto Figueiredo, Marianne Manjavachi, João B Calixto
The kinin receptor B1 and the transient receptor potential ankyrin 1 (TRPA1) work as initiators and gatekeepers of nociception and inflammation. This study reports that the nociceptive transmission induced by activation of B1 receptor is dependent on TRPA1 ion channel. The mechanical hyperalgesia was induced by intrathecal (i.t.) injection of B1 agonist des-Arginine(9)-bradykinin (DABK) or TRPA1 agonist cinnamaldehyde and was evaluated by the withdrawal response after von Frey Hair application in the hind paw...
November 4, 2016: Biochemical Pharmacology
https://www.readbyqxmd.com/read/27821666/duck-tembusu-virus-nonstructural-protein-1-antagonizes-ifn-%C3%AE-signaling-pathways-by-targeting-visa
#14
Junyong Wang, Cao-Qi Lei, Yanhong Ji, Hongbo Zhou, Yujie Ren, Qianqian Peng, Yan Zeng, Yane Jia, Jinying Ge, Bo Zhong, Yu Li, Jianzhong Wei, Hong-Bing Shu, Qiyun Zhu
Duck Tembusu virus (DTMUV) is an emergent infectious pathogen that has caused severe disease in ducks and huge economic losses to the poultry industry in China since 2009. Previously, we showed that DTMUV inhibits IFN-β induction early in infection; however, the mechanisms of the inhibition of innate immune responses remain poorly understood. In this study, we screened DTMUV-encoded structural and nonstructural proteins using reporter assays and found that DTMUV NS1 markedly suppressed virus-triggered IFN-β expression by inhibiting retinoic acid-inducible gene I-like receptor signaling...
November 7, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27820851/appl1-mediating-leptin-signaling-contributes-to-proliferation-and-migration-of-cancer-cells
#15
Youming Ding, Yingkang Cao, Bin Wang, Lei Wang, Yemin Zhang, Deling Zhang, Xiaoyan Chen, Mingxin Li, Changhua Wang
Leptin has been implicated in tumorigenesis and tumor progression, particularly in obese patients. As a multifunctional adaptor protein, APPL1 (containing pleckstrin homology domain, phosphotyrosine binding domain, and a leucine zipper motif 1) plays a critical role in regulating adiponectin and insulin signaling pathways. Currently, high APPL1 level has been suggested to be related to metastases and progression of some types of cancer. However, the intercourse between leptin signaling pathway and APPL1 remains poorly understood...
2016: PloS One
https://www.readbyqxmd.com/read/27820798/dpp8-and-dpp9-inhibition-induces-pro-caspase-1-dependent-monocyte-and-macrophage-pyroptosis
#16
Marian C Okondo, Darren C Johnson, Ramya Sridharan, Eun Bin Go, Ashley J Chui, Mitchell S Wang, Sarah E Poplawski, Wengen Wu, Yuxin Liu, Jack H Lai, David G Sanford, Michael O Arciprete, Todd R Golub, William W Bachovchin, Daniel A Bachovchin
Val-boroPro (Talabostat, PT-100), a nonselective inhibitor of post-proline cleaving serine proteases, stimulates mammalian immune systems through an unknown mechanism of action. Despite this lack of mechanistic understanding, Val-boroPro has attracted substantial interest as a potential anticancer agent, reaching phase 3 trials in humans. Here we show that Val-boroPro stimulates the immune system by triggering a proinflammatory form of cell death in monocytes and macrophages known as pyroptosis. We demonstrate that the inhibition of two serine proteases, DPP8 and DPP9, activates the pro-protein form of caspase-1 independent of the inflammasome adaptor ASC...
November 7, 2016: Nature Chemical Biology
https://www.readbyqxmd.com/read/27819682/ripk1-inhibits-zbp1-driven-necroptosis-during-development
#17
Kim Newton, Katherine E Wickliffe, Allie Maltzman, Debra L Dugger, Andreas Strasser, Victoria C Pham, Jennie R Lill, Merone Roose-Girma, Søren Warming, Margaret Solon, Hai Ngu, Joshua D Webster, Vishva M Dixit
Receptor-interacting protein kinase 1 (RIPK1) promotes cell survival-mice lacking RIPK1 die perinatally, exhibiting aberrant caspase-8-dependent apoptosis and mixed lineage kinase-like (MLKL)-dependent necroptosis. However, mice expressing catalytically inactive RIPK1 are viable, and an ill-defined pro-survival function for the RIPK1 scaffold has therefore been proposed. Here we show that the RIP homotypic interaction motif (RHIM) in RIPK1 prevents the RHIM-containing adaptor protein ZBP1 (Z-DNA binding protein 1; also known as DAI or DLM1) from activating RIPK3 upstream of MLKL...
December 1, 2016: Nature
https://www.readbyqxmd.com/read/27813153/traf6-mediates-suppression-of-osteoclastogenesis-and-prevention-of-ovariectomy-induced-bone-loss-by-a-novel-prenylflavonoid
#18
E M Tan, L Li, I R Indran, N Chew, E L Yong
Given the limitations of current therapeutic options for postmenopausal osteoporosis, there is a need for alternatives with minimal adverse effects. In this study, we evaluated the effects of icaritin (ICT), a natural prenylflavonoid, on osteoclastogenesis both in vitro and in an ovariectomized (OVX)-rat model, and investigated its underlying molecular mechanism(s) of action. ICT inhibited osteoclast formation in two osteoclast precursor models, RAW 264.7 mouse monocyte cell line and human PBMC. ICT also inhibited sealing zone and resorption pit formation in a dose-dependent manner...
November 4, 2016: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/27807832/transcriptome-and-proteome-analyses-of-tnfaip8-knockdown-cancer-cells-reveal-new-insights-into-molecular-determinants-of-cell-survival-and-tumor-progression
#19
Timothy F Day, Rajshree R Mewani, Joshua Starr, Xin Li, Debyani Chakravarty, Habtom Ressom, Xiaojun Zou, Ofer Eidelman, Harvey B Pollard, Meera Srivastava, Usha N Kasid
Tumor necrosis factor-α-inducible protein 8 (TNFAIP8) is the first discovered oncogenic and an anti-apoptotic member of a conserved TNFAIP8 or TIPE family of proteins. TNFAIP8 mRNA is induced by NF-kB, and overexpression of TNFAIP8 has been correlated with poor prognosis in many cancers. Downregulation of TNFAIP8 expression has been associated with decreased pulmonary colonization of human tumor cells, and enhanced sensitivities of tumor xenografts to radiation and docetaxel. Here we have investigated the effects of depletion of TNFAIP8 on the mRNA, microRNA and protein expression profiles in prostate and breast cancers and melanoma...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27807399/electric-stimulation-of-the-vagus-nerve-reduced-mouse-neuroinflammation-induced-by-lipopolysaccharide
#20
G Meneses, M Bautista, A Florentino, G Díaz, G Acero, H Besedovsky, D Meneses, A Fleury, A Del Rey, G Gevorkian, G Fragoso, E Sciutto
BACKGROUND: Neuroinflammation (NI) is a key feature in the pathogenesis and progression of infectious and non-infectious neuropathologies, and its amelioration usually improves the patient outcome. Peripheral inflammation may promote NI through microglia and astrocytes activation, an increased expression of inflammatory mediators and vascular permeability that may lead to neurodegeneration. Several anti-inflammatory strategies have been proposed to control peripheral inflammation. Among them, electrical stimulation of the vagus nerve (VNS) recently emerged as an alternative to effectively attenuate peripheral inflammation in a variety of pathological conditions with few side effects...
2016: Journal of Inflammation
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