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https://www.readbyqxmd.com/read/29247407/zfyve16-regulates-the-proliferation-of-b-lymphoid-cells
#1
Xuemei Zhao, Donghe Li, Qingsong Qiu, Bo Jiao, Ruihong Zhang, Ping Liu, Ruibao Ren
Zfyve16 (a.k.a. endofin or endosome-associated FYVE-domain protein), a member of the FYVE-domain protein family, is involved in endosomal trafficking and in TGF-β, BMP, and EGFR signaling. The FYVE protein SARA regulates the TGF-β signaling pathway by recruiting Smad2/3 and accelerating their phosphorylation, thereby altering their susceptibility to TGF-β-mediated T cell suppression. Zfyve16 binds to Smad4 and their binding affects the formation of Smad2/3-Smad4 complex in TGF-β signaling. However, the in vivo function of Zfyve16 remains unknown...
December 16, 2017: Frontiers of Medicine
https://www.readbyqxmd.com/read/29243584/prediction-and-analysis-of-three-dimensional-structure-of-the-p7-transactivated-protein1-of-hepatitis-c-virus
#2
Mahmoud M Elhefnawi, Mohamed E Hasan, Amal Mahmoud, Yehia A Khidr, El-Sayed A El-Absawy, Alaa A Hemeida
BACKGROUND: The p7-transactivated protein of Hepatitis C virus is a small integral membrane protein of 127 amino acids, which is crucial for assembly and release of infectious virions. Ab initio and comparative modelling, is an essential tool to solve the problem of protein structure prediction and to comprehend the physicochemical fundemental of how proteins fold in nature. RESULTS: Only one domain (1-127) of p7 had been predicted using the systematic in silico approach, ThreaDom...
December 15, 2017: Infectious Disorders Drug Targets
https://www.readbyqxmd.com/read/29207637/wheat-germ-agglutinin-induced-paraptosis-like-cell-death-and-protective-autophagy-is-mediated-by-autophagy-linked-fyve-inhibition
#3
Tsung Lin Tsai, Hao Chen Wang, Chun Hua Hung, Peng Chan Lin, Yi San Lee, Helen H W Chen, Wu Chou Su
Wheat germ agglutinin (WGA) is a lectin that specifically binds cell surface glycoproteins and disrupts nuclear pore complex function through its interaction with POM121. Our data indicate WGA induces paraptosis-like cell death without caspase activation. We observed the main features of paraptosis, including cytoplasmic vacuolation, endoplasmic reticulum dilation and increased ER stress, and the unfolded protein response in WGA-treated cervical carcinoma cells. Conversion of microtubule-associated protein I light chain 3 (LC3-I) into LC3-II and punctuate formation suggestive of autophagy were observed in WGA-treated cells...
October 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/29163768/inhibitor-of-growth-protein-4-interacts-with-beclin-1-and-represses-autophagy
#4
Valentina Sica, José Manuel Bravo-San Pedro, Guo Chen, Guillermo Mariño, Sylvie Lachkar, Valentina Izzo, Maria Chiara Maiuri, Mireia Niso-Santano, Guido Kroemer
Beclin 1 (BECN1) is a multifunctional protein that activates the pro-autophagic class III phosphatidylinositol 3-kinase (PIK3C3, best known as VPS34), yet also interacts with multiple negative regulators. Here we report that BECN1 interacts with inhibitor of growth family member 4 (ING4), a tumor suppressor protein that is best known for its capacity to interact with the tumor suppressor protein p53 (TP53) and the acetyltransferase E1A binding protein p300 (EP300). Removal of TP53 or EP300 did not affect the BECN1/ING4 interaction, which however was lost upon culture of cells in autophagy-inducing, nutrient free conditions...
October 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/29089386/rufy3-is-an-adapter-protein-for-small-gtpases-that-activates-a-rac-guanine-nucleotide-exchange-factor-to-control-neuronal-polarity
#5
Atsuko Honda, Hiroshi Usui, Kenji Sakimura, Michihiro Igarashi
RUN and FYVE domain-containing 3 (Rufy3) is an adapter protein for small GTPase proteins and is bound to activated Rap2, a Ras family protein in the developing neuron. Previously, we reported the presence of a rapid cell polarity determination mechanism involving Rufy3, which is likely required for in vivo neuronal development. However, the molecular details of this mechanism are unclear. To this end, here we produced Rufy3 knockout (Rufy3-KO) mice to study the role of Rufy3 in more detail. Examining Rufy3-KO neurons, we found that Rufy3 is recruited via glycoprotein M6A (GPM6a) to detergent-resistant membrane domains, which are biochemically similar to lipid rafts...
October 31, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29084199/class-iii-phosphatidylinositol-3-oh-kinase-controls-epithelial-integrity-through-endosomal-lkb1-regulation
#6
Fergal O'Farrell, Viola Hélène Lobert, Marte Sneeggen, Ashish Jain, Nadja Sandra Katheder, Eva Maria Wenzel, Sebastian Wolfgang Schultz, Kia Wee Tan, Andreas Brech, Harald Stenmark, Tor Erik Rusten
The molecular mechanisms underlying the interdependence between intracellular trafficking and epithelial cell polarity are poorly understood. Here we show that inactivation of class III phosphatidylinositol-3-OH kinase (CIII-PI3K), which produces phosphatidylinositol-3-phosphate (PtdIns3P) on endosomes, disrupts epithelial organization. This is caused by dysregulation of endosomally localized Liver Kinase B1 (LKB1, also known as STK11), which shows delocalized and increased activity accompanied by dysplasia-like growth and invasive behaviour of cells provoked by JNK pathway activation...
October 30, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/29021535/the-autophagy-scaffold-protein-alfy-is-critical-for-the-granulocytic-differentiation-of-aml-cells
#7
Anna M Schläfli, Pauline Isakson, E Garattini, Anne Simonsen, Mario P Tschan
Acute myeloid leukemia (AML) is a malignancy of myeloid progenitor cells that are blocked in differentiation. Acute promyelocytic leukemia (APL) is a rare form of AML, which generally presents with a t(15;17) translocation causing expression of the fusion protein PML-RARA. Pharmacological doses of all-trans retinoic acid (ATRA) induce granulocytic differentiation of APL cells leading to cure rates of >80% if combined with conventional chemotherapy. Autophagy is a lysosomal degradation pathway for the removal of cytoplasmic content and recycling of macromolecules...
October 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28993463/pib2-and-ego-complex-are-both-required-for-activation-of-torc1
#8
Natalia V Varlakhanova, Michael Mihalevic, Kara A Bernstein, Marijn G J Ford
The TORC1 complex is a key regulator of cell growth and metabolism in Saccharomyces cerevisiae The vacuole-associated EGO Complex couples activation of TORC1 to the availability of amino acids, specifically glutamine and leucine. EGO Complex is also essential for reactivation of TORC1 following rapamycin-induced growth arrest and for its distribution on the vacuolar membrane. Pib2, a FYVE-containing PI3P-binding protein, is a newly-discovered and poorly characterized activator of TORC1. Here, we show that Pib2 is required for reactivation of TORC1 following rapamycin-induced growth arrest...
October 9, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28982592/human-amyloid-%C3%AE-peptide-and-tau-co-expression-impairs-behavior-and-causes-specific-gene-expression-changes-in-caenorhabditis-elegans
#9
Chenyin Wang, Valeria Saar, Ka Lai Leung, Liang Chen, Garry Wong
Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by the presence of extracellular amyloid plaques consisting of Amyloid-β peptide (Aβ) aggregates and neurofibrillary tangles formed by aggregation of hyperphosphorylated microtubule-associated protein tau. We generated a novel invertebrate model of AD by crossing Aβ1-42 (strain CL2355) with either pro-aggregating tau (strain BR5270) or anti-aggregating tau (strain BR5271) pan-neuronal expressing transgenic Caenorhabditis elegans...
October 2, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28906046/the-unique-n-terminal-zinc-finger-of-synaptotagmin-like-protein-4-reveals-fyve-structure
#10
Kazuhide Miyamoto, Arisa Nakatani, Kazuki Saito
Synaptotagmin-like protein 4 (Slp4), expressed in human platelets, is associated with dense granule release. Slp4 is comprised of the N-terminal zinc finger, Slp homology domain, and C2 domains. We synthesized a compact construct (the Slp4N peptide) corresponding to the Slp4 N-terminal zinc finger. Herein, we have determined the solution structure of the Slp4N peptide by nuclear magnetic resonance (NMR). Furthermore, experimental, chemical modification of Cys residues revealed that the Slp4N peptide binds two zinc atoms to mediate proper folding...
September 14, 2017: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/28819237/disruption-of-the-plant-specific-cfs1-gene-impairs-autophagosome-turnover-and-triggers-eds1-dependent-cell-death
#11
Arpaporn Sutipatanasomboon, Stefanie Herberth, Ellen G Alwood, Heidrun Häweker, Britta Müller, Mojgan Shahriari, Anke Y Zienert, Birger Marin, Silke Robatzek, Gerrit J K Praefcke, Kathryn R Ayscough, Martin Hülskamp, Swen Schellmann
Cell death, autophagy and endosomal sorting contribute to many physiological, developmental and immunological processes in plants. They are mechanistically interconnected and interdependent, but the molecular basis of their mutual regulation has only begun to emerge in plants. Here, we describe the identification and molecular characterization of CELL DEATH RELATED ENDOSOMAL FYVE/SYLF PROTEIN 1 (CFS1). The CFS1 protein interacts with the ENDOSOMAL SORTING COMPLEX REQUIRED FOR TRANSPORT I (ESCRT-I) component ELCH (ELC) and is localized at ESCRT-I-positive late endosomes likely through its PI3P and actin binding SH3YL1 Ysc84/Lsb4p Lsb3p plant FYVE (SYLF) domain...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28813193/local-detection-of-ptdins3p-at-autophagosome-biogenesis-membrane-platforms
#12
Anna Chiara Nascimbeni, Patrice Codogno, Etienne Morel
Phosphatidylinositol 3-phosphate (PtdIns3P) is a key player of membrane trafficking regulation, mostly synthesized by the PIK3C3 lipid kinase. The presence of PtdIns3P on endosomes has been demonstrated; however, the role and dynamics of the pool of PtdIns3P dedicated to macroautophagy/autophagy remains elusive. Here we addressed this question by studying the mobilization of PtdIns3P in time and space during autophagosome biogenesis. We compared different dyes known to specifically detect PtdIns3P by fluorescence microscopy analysis, based on PtdIns3P-binding FYVE and PX domains, and show that these transfected dyes induce defects in endosomal dynamics as well as artificial and sustained autophagosome formation...
September 2, 2017: Autophagy
https://www.readbyqxmd.com/read/28757133/corrigendum-to-autophagy-linked-fyve-containing-protein-wdfy3-interacts-with-traf6-and-modulates-rankl-induced-osteoclastogenesis-j-autoimmun-73c-2016-73-84
#13
Dennis J Wu, Ran Gu, Ritu Sarin, Regina Zavodovskaya, Chia-Pei Chen, Blaine A Christiansen, Konstantinos S Zarbalis, Iannis E Adamopoulos
No abstract text is available yet for this article.
November 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28723271/development-of-three-orthogonal-assays-suitable-for-the-identification-and-qualification-of-pikfyve-inhibitors
#14
Kylie Fogarty, Mohammed Kashem, Andras Bauer, Alexandra Bernardino, Debra Brennan, Brian Cook, Neil Farrow, Teresa Molinaro, Richard Nelson
FYVE-type zinc finger-containing phosphoinositide kinase (PIKfyve) catalyzes the formation of phosphatidylinositol 3,5-bisphosphate (PI(3,5)P2) from phosphatidylinositol 3-phosphate (PI(3)P). PIKfyve has been implicated in multiple cellular processes, and its role in the regulation of toll-like receptor (TLR) pathways and the production of proinflammatory cytokines has sparked interest in developing small-molecule PIKfyve inhibitors as potential therapeutics to treat autoimmune and inflammatory diseases. We developed three orthogonal assays to identify and qualify small-molecule inhibitors of PIKfyve: (1) a purified component microfluidic enzyme assay that measures the conversion of fluorescently labeled PI(3)P to PI(3,5)P2 by purified recombinant full-length human 6His-PIKfyve (rPIKfyve); (2) an intracellular protein stabilization assay using the kinase domain of PIKfyve expressed in HEK293 cells; and (3) a cell-based functional assay that measures the production of interleukin (IL)-12p70 in human peripheral blood mononuclear cells stimulated with TLR agonists lipopolysaccharide and R848...
July 2017: Assay and Drug Development Technologies
https://www.readbyqxmd.com/read/28706153/inhibitor-of-growth-protein-4-interacts-with-beclin-1-and-represses-autophagy
#15
Valentina Sica, José Manuel Bravo-San Pedro, Guo Chen, Guillermo Mariño, Sylvie Lachkar, Valentina Izzo, Maria Chiara Maiuri, Mireia Niso-Santano, Guido Kroemer
Beclin 1 (BECN1) is a multifunctional protein that activates the pro-autophagic class III phosphatidylinositol 3-kinase (PIK3C3, best known as VPS34), yet also interacts with multiple negative regulators. Here we report that BECN1 interacts with inhibitor of growth family member 4 (ING4), a tumor suppressor protein that is best known for its capacity to interact with the tumor suppressor protein p53 (TP53) and the acetyltransferase E1A binding protein p300 (EP300). Removal of TP53 or EP300 did not affect the BECN1/ING4 interaction, which however was lost upon culture of cells in autophagy-inducing, nutrient free conditions...
July 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28588446/purkinje-cell-degeneration-and-motor-coordination-deficits-in-a-new-mouse-model-of-autosomal-recessive-spastic-ataxia-of-charlevoix-saguenay
#16
Man Ding, Chao Weng, Shanghua Fan, Qian Cao, Zuneng Lu
Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is an early-onset neurodegenerative disorder. In 2007, a novel locus, SAX2, which is located on chromosome 17p13 and contains 3 genes, ankyrin repeat and FYVE domain-containing 1 (ANKFY1), β-arrestin 2 (ARRB2) and kinesin family member 1C (KIF1C), was linked to ARSACS. We generated Ankfy1 heterozygous (Ankfy1/+) mice to establish an animal model and examine the pathophysiological basis of ARSACS. The transgenic mice displayed an abnormal gait with progressive motor and cerebellar nerve dysfunction that was highly reminiscent of ARSACS...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28587322/novel-variant-in-the-fgd1-gene-causing-aarskog-scott-syndrome
#17
Yihua Ge, Niu Li, Zhigang Wang, Jian Wang, Haiqing Cai
Aarskog-Scott syndrome (ASS) is a rare, X-linked recessive inherited disorder. Affected individuals may develop short stature and exhibit distinctive skeletal and genital development. Mutations in the FYVE, rhogef and pleckstrin homology domain-containing protein 1 (FGD1) gene, located within the Xp11.21 region, are responsible for the occurrence of ASS. Since it is rare and complex, it can take a long time to obtain a definitive clinical diagnosis unless clinicians are familiar with the disease. In the present study, whole-exome sequencing (WES) was performed to screen for causal variants in a Chinese pediatric patient who exhibited a number of clinical symptoms of ASS, including short stature, facial abnormalities, stubby metacarpals and swollen testis...
June 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28483912/an-in-vitro-torc1-kinase-assay-that-recapitulates-the-gtr-independent-glutamine-responsive-torc1-activation-mechanism-on-yeast-vacuoles
#18
Mirai Tanigawa, Tatsuya Maeda
Evolutionarily conserved target of rapamycin (TOR) complex 1 (TORC1) responds to nutrients, especially amino acids, to promote cell growth. In the yeast Saccharomyces cerevisiae, various nitrogen sources activate TORC1 with different efficiencies, although the mechanism remains elusive. Leucine, and perhaps other amino acids, was reported to activate TORC1 via the heterodimeric small GTPases Gtr1-Gtr2, the orthologues of the mammalian Rag GTPases. More recently, an alternative Gtr-independent TORC1 activation mechanism that may respond to glutamine was reported, although its molecular mechanism is not clear...
July 15, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28406455/subcellular-localization-of-arabidopsis-pathogenesis-related-1-pr1-protein
#19
Tamara Pečenková, Roman Pleskot, Viktor Žárský
The Arabidopsisthaliana pathogenesis-related 1 (PR1) is an important defense protein, so far it has only been detected in extracellular space and its subcellular sorting and transport remain unexplained. Using a green fluorescent protein (GFP) tagged full length, as well as a C-terminus truncated version of PR1, we observed that when expressed ectopically in Nicotiana benthamiana leaves, PR1 co-localizes only partially with Golgi markers, and much more prominently with the late endosome (LE)/multivesicular body (MVB) FYVE marker...
April 13, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28381171/identification-and-validation-of-a-novel-autophagy-gene-expression-signature-for-human-bladder-cancer-patients
#20
Sanaa Eissa, Marwa Matboli, Nahla Awad, Yousif Kotb
We sought to identify and validate a novel urinary autophagy transcript signature in patients with bladder cancer and evaluate its clinical utility. We performed an initial screening for seven autophagy transcript-based panel (autophagy-related protein 12 (ATG12); WD repeat domain, phosphoinositide interacting 2 (WIPI2); FYVE and coiled-coil domain-containing protein 1 (FYCO1); microtubule-associated protein light chain (MAPLC3); RB1-inducible coiled-coil 1 (RB1CC1); tachylectin-II-like beta-propeller domain 1 (TECPR1); and Unc-51-like kinase (ULK1)) that was identified based on bioinformatics analysis followed by SYBR Green-based polymerase chain reaction array validation in paired tissue and urine samples...
April 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
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