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https://www.readbyqxmd.com/read/29163766/epigallocatechin-3-gallate-egcg-up-regulates-mir-15b-expression-thus-attenuating-store-operated-calcium-entry-soce-into-murine-cd4-t-cells-and-human-leukaemic-t-cell-lymphoblasts
#1
Shaqiu Zhang, Tamer Al-Maghout, Rosi Bissinger, Ni Zeng, Lisann Pelzl, Madhuri S Salker, Anchun Cheng, Yogesh Singh, Florian Lang
CD4(+) T cells are key elements in immune responses and inflammation. Activation of T cell receptors in CD4(+) T cells triggers cytosolic Ca(2+) release with subsequent store operated Ca(2+) entry (SOCE), which is accomplished by the pore forming Ca(2+) release activated Ca(2+) (CRAC) channel Orai1 and its regulator stromal cell-interaction molecule 2 (STIM2). Green tea polyphenol epigallocatechin-3-gallate (EGCG) acts as a potent anti-inflammatory and anti-oxidant agent for various types of cells including immune cells...
October 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/29158810/phosphorylated-protein-kinase-c-zeta-lambda-expression-in-colorectal-adenocarcinoma-and-its-correlation-with-clinicopathologic-characteristics-and-prognosis
#2
Min-Kyung Yeo, Ji Yeon Kim, In-Ock Seong, Jin-Man Kim, Kyung-Hee Kim
Background: Protein kinase C zeta/lambda (PKCζ/λ) is a family of protein kinase enzymes that contributes to cell proliferation and regulation, which are important for cancer development. PKCζ/λ has been shown to be an important regulator of tumorigenesis in intestinal cancer. The phosphorylated form of PKCζ/λ, p-PKCζ/λ, is suggested as an active form of PKCζ/λ. However, p-PKCζ/λ expression and its clinicopathologic implication in colorectal adenocarcinoma (CRAC) are unclear. Methods: Seven whole-tissue sections of malignant polyps containing both non-neoplastic and neoplastic mucosa, 11 adenomas with low-grade dysplasia, and 173 CRACs were examined by immunohistochemistry and western blot assay for p-PKCζ/λ protein expression...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/29155098/orai1-mutations-abolishing-store-operated-ca-2-entry-cause-anhidrotic-ectodermal-dysplasia-with-immunodeficiency-eda-id
#3
Jayson Lian, Mario Cuk, Sascha Kahlfuss, Lina Kozhaya, Martin Vaeth, Frédéric Rieux-Laucat, Capucine Picard, Melina J Benson, Antonia Jakovcevic, Karmen Bilic, Iva Martinac, Peter Stathopulos, Imre Kacskovics, Thomas Vraetz, Carsten Speckmann, Stephan Ehl, Thomas Issekutz, Derya Unutmaz, Stefan Feske
BACKGROUND: Store-operated Ca(2+) entry (SOCE) through Ca(2+) release-activated Ca(2+) (CRAC) channels is an essential signaling pathway in many cell types. CRAC channels are formed by ORAI1, ORAI2 and ORAI3 proteins and activated by stromal interaction molecule 1 (STIM1) and STIM2. Mutations in ORAI1 and STIM1 genes that abolish SOCE cause a combined immunodeficiency (CID) syndrome that is accompanied by autoimmunity and non-immunological symptoms. OBJECTIVE: Molecular and immunological analysis of patients with CID, anhidrosis and ectodermal dysplasia of unknown etiology...
November 15, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29112302/tmd1-domain-and-crac-motif-determine-the-association-and-disassociation-of-mxirt1-with-detergent-resistant-membranes
#4
Song Tan, Peng Zhang, Wei Xiao, Bing Feng, Lan-You Chen, Shuang Li, Peng Li, Wei-Zhong Zhao, Xiao-Ting Qi, Li-Ping Yin
Iron is essential for most living organisms. The iron-regulated transporter1 (IRT1) plays a major role in iron uptake in roots, and its trafficking from endoplasmic reticulum (ER) to plasma membrane (PM) is tightly coordinated with changes in iron environment. However, studies on IRT1 response are limited. Here, we report that Malus xiaojinesis IRT1 (MxIRT1) associates with detergent-resistant membranes (DRMs, a biochemical counterpart of PM microdomains), whereas the PM microdomains are known platforms for signal transduction in the PM...
November 7, 2017: Traffic
https://www.readbyqxmd.com/read/29071121/binding-to-rna-regulates-set1-function
#5
Pierre Luciano, Jongcheol Jeon, Abdessamad El-Kaoutari, Drice Challal, Amandine Bonnet, Mara Barucco, Tito Candelli, Frederic Jourquin, Pascale Lesage, Jaehoon Kim, Domenico Libri, Vincent Géli
The Set1 family of histone H3 lysine 4 (H3K4) methyltransferases is highly conserved from yeast to human. Here we show that the Set1 complex (Set1C) directly binds RNA in vitro through the regions that comprise the double RNA recognition motifs (dRRM) and N-SET domain within Set1 and its subunit Spp1. To investigate the functional relevance of RNA binding, we performed UV RNA crosslinking (CRAC) for Set1 and RNA polymerase II in parallel with ChIP-seq experiments. Set1 binds nascent transcripts through its dRRM...
2017: Cell Discovery
https://www.readbyqxmd.com/read/29051200/human-mettl16-is-a-n-6-methyladenosine-m-6-a-methyltransferase-that-targets-pre-mrnas-and-various-non-coding-rnas
#6
Ahmed S Warda, Jens Kretschmer, Philipp Hackert, Christof Lenz, Henning Urlaub, Claudia Höbartner, Katherine E Sloan, Markus T Bohnsack
N(6)-methyladenosine (m(6)A) is a highly dynamic RNA modification that has recently emerged as a key regulator of gene expression. While many m(6)A modifications are installed by the METTL3-METTL14 complex, others appear to be introduced independently, implying that additional human m(6)A methyltransferases remain to be identified. Using crosslinking and analysis of cDNA (CRAC), we reveal that the putative human m(6)A "writer" protein METTL16 binds to the U6 snRNA and other ncRNAs as well as numerous lncRNAs and pre-mRNAs...
November 2017: EMBO Reports
https://www.readbyqxmd.com/read/29030115/store-operated-ca-2-entry-controls-clonal-expansion-of-t-cells-through-metabolic-reprogramming
#7
Martin Vaeth, Mate Maus, Stefan Klein-Hessling, Elizaveta Freinkman, Jun Yang, Miriam Eckstein, Scott Cameron, Stuart E Turvey, Edgar Serfling, Friederike Berberich-Siebelt, Richard Possemato, Stefan Feske
Store-operated Ca(2+) entry (SOCE) is the main Ca(2+) influx pathway in lymphocytes and is essential for T cell function and adaptive immunity. SOCE is mediated by Ca(2+) release-activated Ca(2+) (CRAC) channels that are activated by stromal interaction molecule (STIM) 1 and STIM2. SOCE regulates many Ca(2+)-dependent signaling molecules, including calcineurin, and inhibition of SOCE or calcineurin impairs antigen-dependent T cell proliferation. We here report that SOCE and calcineurin regulate cell cycle entry of quiescent T cells by controlling glycolysis and oxidative phosphorylation...
October 17, 2017: Immunity
https://www.readbyqxmd.com/read/29019677/scalaradial-is-a-potent-inhibitor-of-transient-receptor-potential-melastatin-2-trpm2-ion-channels
#8
John G Starkus, Peter Poerzgen, Kristine Layugan, Kelly Galbraith Kawabata, Jun-Ichi Goto, Sayuri Suzuki, George Myers, Michelle Kelly, Reinhold Penner, Andrea Fleig, F David Horgen
TRPM2 is a Ca(2+)-permeable, nonselective cation channel that plays a role in oxidant-induced cell death, insulin secretion, and cytokine release. Few TRPM2 inhibitors have been reported, which hampers the validation of TRPM2 as a drug target. While screening our in-house marine-derived chemical library, we identified scalaradial and 12-deacetylscalaradial as the active components within an extract of an undescribed species of Cacospongia (class Demospongiae, family Thorectidae) that strongly inhibited TRPM2-mediated Ca(2+) influx in TRPM2-overexpressing HEK293 cells...
October 27, 2017: Journal of Natural Products
https://www.readbyqxmd.com/read/28900926/immunological-disorders-regulation-of-ca-2-signaling-in-t-lymphocytes
#9
Sonal Srikanth, Jin Seok Woo, Zuoming Sun, Yousang Gwack
Engagement of T cell receptors (TCRs) with cognate antigens triggers cascades of signaling pathways in helper T cells. TCR signaling is essential for the effector function of helper T cells including proliferation, differentiation, and cytokine production. It also modulates effector T cell fate by inducing cell death, anergy (nonresponsiveness), exhaustion, and generation of regulatory T cells. One of the main axes of TCR signaling is the Ca(2+)-calcineurin-nuclear factor of activated T cells (NFAT) signaling pathway...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28900914/stim-trp-pathways-and-microdomain-organization-contribution-of-trpc1-in-store-operated-ca-2-entry-impact-on-ca-2-signaling-and-cell-function
#10
Hwei Ling Ong, Indu S Ambudkar
Store-operated calcium entry (SOCE) is a ubiquitous Ca(2+) entry pathway that is activated in response to depletion of ER-Ca(2+) stores and critically controls the regulation of physiological functions in a wide variety of cell types. The transient receptor potential canonical (TRPC) channels (TRPCs 1-7), which are activated by stimuli leading to PIP2 hydrolysis, were first identified as molecular components of SOCE channels. While TRPC1 was associated with SOCE and regulation of function in several cell types, none of the TRPC members displayed I CRAC, the store-operated current identified in lymphocytes and mast cells...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28900912/the-stim-orai-pathway-light-operated-ca-2-entry-through-engineered-crac-channels
#11
Guolin Ma, Shufan Wen, Yun Huang, Yubin Zhou
Ca(2+) signals regulate a plethora of cellular functions that include muscle contraction, heart beating, hormone secretion, lymphocyte activation, gene expression, and metabolism. To study the impact of Ca(2+) signals on biological processes, pharmacological tools and caged compounds have been commonly applied to induce fluctuations of intracellular Ca(2+) concentrations. These conventional approaches, nonetheless, lack rapid reversibility and high spatiotemporal resolution. To overcome these disadvantages, we and others have devised a series of photoactivatable genetically encoded Ca(2+) actuators (GECAs) by installing light sensitivities into a bona fide highly selective Ca(2+) channel, the Ca(2+) release-activated Ca(2+) (CRAC) channel...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28900908/the-stim-orai-pathway-orai-the-pore-forming-subunit-of-the-crac-channel
#12
Aparna Gudlur, Patrick G Hogan
This chapter focuses on the Orai proteins, Orai1-Orai3, with special emphasis on Orai1, in humans and other mammals, and on the definitive evidence that Orai is the pore subunit of the CRAC channel. It begins by reviewing briefly the defining characteristics of the CRAC channel, then discusses the studies that implicated Orai as part of the store-operated Ca(2+) entry pathway and as the CRAC channel pore subunit, and finally examines ongoing work that is providing insights into CRAC channel structure and gating...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28863821/relevance-of-carc-and-crac-cholesterol-recognition-motifs-in-the-nicotinic-acetylcholine-receptor-and-other-membrane-bound-receptors
#13
Coralie Di Scala, Carlos J Baier, Luke S Evans, Philip T F Williamson, Jacques Fantini, Francisco J Barrantes
Cholesterol is a ubiquitous neutral lipid, which finely tunes the activity of a wide range of membrane proteins, including neurotransmitter and hormone receptors and ion channels. Given the scarcity of available X-ray crystallographic structures and the even fewer in which cholesterol sites have been directly visualized, application of in silico computational methods remains a valid alternative for the detection and thermodynamic characterization of cholesterol-specific sites in functionally important membrane proteins...
2017: Current Topics in Membranes
https://www.readbyqxmd.com/read/28851859/regulation-of-orai1-stim1-mediated-icrac-by-intracellular-ph
#14
D Gavriliouk, N R Scrimgeour, S Grigoryev, L Ma, F H Zhou, G J Barritt, G Y Rychkov
Ca(2+) release activated Ca(2+) (CRAC) channels composed of two cellular proteins, Ca(2+)-sensing stromal interaction molecule 1 (STIM1) and pore-forming Orai1, are the main mediators of the Ca(2+) entry pathway activated in response to depletion of intracellular Ca(2+) stores. Previously it has been shown that the amplitude of CRAC current (ICRAC) strongly depends on extracellular and intracellular pH. Here we investigate the intracellular pH (pHi) dependence of ICRAC mediated by Orai1 and STIM1ectopically expressed in HEK293 cells...
August 29, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28839199/the-conserved-tyrosine-residue-940-plays-a-key-structural-role-in-membrane-interaction-of-bordetella-adenylate-cyclase-toxin
#15
Jiri Masin, Jana Roderova, Adriana Osickova, Petr Novak, Ladislav Bumba, Radovan Fiser, Peter Sebo, Radim Osicka
The adenylate cyclase toxin-hemolysin (CyaA, ACT or AC-Hly) translocates its adenylate cyclase (AC) enzyme domain into target cells in a step that depends on membrane cholesterol content. We thus examined what role in toxin activities is played by the five putative cholesterol recognition amino acid consensus (CRAC) motifs predicted in CyaA hemolysin moiety. CRAC-disrupting phenylalanine substitutions had no impact on toxin activities and these were not inhibited by free cholesterol, showing that the putative CRAC motifs are not involved in cholesterol binding...
August 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28748221/rna-substrate-length-as-an-indicator-of-exosome-interactions-in-vivo
#16
Clémentine Delan-Forino, Claudia Schneider, David Tollervey
Background: The exosome complex plays key roles in RNA processing and degradation in Eukaryotes and Archaea. Outstanding structural studies identified multiple pathways for RNA substrates into the exosome in vitro, but identifying the pathway followed by individual RNA species in vivo remains challenging. Methods: We attempted to address this question using RNase protection. In vivo RNA-protein crosslinking (CRAC) was applied to the exosome component Rrp44/Dis3, which has both endonuclease and exonuclease activity...
2017: Wellcome Open Research
https://www.readbyqxmd.com/read/28716825/efficiency-and-safety-of-crac-inhibitors-in-human-rheumatoid-arthritis-xenograft-models
#17
Shuang Liu, Hitoshi Hasegawa, Erika Takemasa, Yasuyuki Suzuki, Keizou Oka, Takeshi Kiyoi, Hiroyuki Takeda, Tomio Ogasawara, Tatsuya Sawasaki, Masaki Yasukawa, Kazutaka Maeyama
Store-operated Ca(2+) release-activated Ca(2+) (CRAC) channels are involved in the pathogenesis of rheumatoid arthritis (RA) and have been studied as therapeutic targets in the management of RA. We investigated the efficacy and safety of CRAC inhibitors, including a neutralizing Ab (hCRACM1-IgG) and YM-58483, in the treatment of RA. Patient-derived T cell and B cell activity was suppressed by hCRACM1-IgG as well as YM-58483. Systemically constant, s.c. infused CRAC inhibitors showed anti-inflammatory activity in a human-NOD/SCID xenograft RA model as well as protective effects against the destruction of cartilage and bone...
September 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28694529/the-production-of-fibroblast-growth-factor-23-is-controlled-by-tgf-%C3%AE-2
#18
Martina Feger, Philipp Hase, Bingbing Zhang, Frank Hirche, Philipp Glosse, Florian Lang, Michael Föller
Transforming growth factor-β (TGF-β) is a cytokine produced by many cell types and implicated in cell growth, differentiation, apoptosis, and inflammation. It stimulates store-operated calcium entry (SOCE) through the calcium release-activated calcium (CRAC) channel Orai1/Stim1 in endometrial Ishikawa cells. Bone cells generate fibroblast growth factor (FGF) 23, which inhibits renal phosphate reabsorption and 1,25(OH)2D3 formation in concert with its co-receptor Klotho. Moreover, Klotho and FGF23 counteract aging and age-related clinical conditions...
July 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28575120/structural-basis-for-5-ets-recognition-by-utp4-at-the-early-stages-of-ribosome-biogenesis
#19
Fabiola R Calviño, Markus Kornprobst, Géza Schermann, Fabienne Birkle, Klemens Wild, Tamas Fischer, Ed Hurt, Yasar Luqman Ahmed, Irmgard Sinning
Eukaryotic ribosome biogenesis begins with the co-transcriptional assembly of the 90S pre-ribosome. The 'U three protein' (UTP) complexes and snoRNP particles arrange around the nascent pre-ribosomal RNA chaperoning its folding and further maturation. The earliest event in this hierarchical process is the binding of the UTP-A complex to the 5'-end of the pre-ribosomal RNA (5'-ETS). This oligomeric complex predominantly consists of β-propeller and α-solenoidal proteins. Here we present the structure of the Utp4 subunit from the thermophilic fungus Chaetomium thermophilum at 2...
2017: PloS One
https://www.readbyqxmd.com/read/28564609/sequential-steps-of-crac-channel-activation
#20
Raz Palty, Zhu Fu, Ehud Y Isacoff
Interaction between the endoplasmic reticulum protein STIM1 and the plasma membrane channel ORAI1 generates calcium signals that are central for diverse cellular functions. How STIM1 binds and activates ORAI1 remains poorly understood. Using electrophysiological, optical, and biochemical techniques, we examined the effects of mutations in the STIM1-ORAI1 activating region (SOAR) of STIM1. We find that SOAR mutants that are deficient in binding to resting ORAI1 channels are able to bind to and boost activation of partially activated ORAI1 channels...
May 30, 2017: Cell Reports
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