keyword
MENU ▼
Read by QxMD icon Read
search

Cgas

keyword
https://www.readbyqxmd.com/read/28214358/the-n-terminus-of-cgas-de-oligomerizes-the-cgas-dna-complex-and-lifts-the-dna-size-restriction-of-core-cgas-activity
#1
Arum Lee, Eun-Byeol Park, Janghyun Lee, Byong-Seok Choi, Suk-Jo Kang
Cyclic GMP-AMP synthase (cGAS) is a DNA-sensing enzyme in the innate immune system. Recent studies using core-cGAS lacking the N-terminus investigated the mechanism for binding of double-stranded (ds) DNA and synthesis of 2',3'-cGAMP, a secondary messenger that ultimately induces type I interferons. However, the function of the N-terminus of cGAS remains largely unknown. Here, we found that the N-terminus enhanced the activity of core-cGAS in vivo. Importantly, the catalytic activity of core-cGAS decreased as the length of dsDNA increased, but the diminished activity was restored by addition of the N-terminus...
February 18, 2017: FEBS Letters
https://www.readbyqxmd.com/read/28202760/restriction-of-hcmv-replication-by-isg15-a-host-effector-regulated-by-cgas-sting-dsdna-sensing
#2
Christopher Bianco, Ian Mohr
Accumulation of the interferon-stimulated gene (ISG) 15 protein product, which is reversibly conjugated to numerous polypeptide targets, impacts the proteome and physiology of uninfected and infected cells. While many viruses, including human cytomegalovirus (HCMV) blunt host antiviral defenses by limiting ISG expression, the overall abundance of ISG15 monomer and protein conjugates rises in HCMV-infected cells. However, the molecular signals underlying ISG15 accumulation and whether the ISG15 polypeptide itself influences HCMV infection biology remain unknown...
February 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28194029/ifi16-and-cgas-cooperate-in-the-activation-of-sting-during-dna-sensing-in-human-keratinocytes
#3
Jessica F Almine, Craig A J O'Hare, Gillian Dunphy, Ismar R Haga, Rangeetha J Naik, Abdelmadjid Atrih, Dympna J Connolly, Jordan Taylor, Ian R Kelsall, Andrew G Bowie, Philippa M Beard, Leonie Unterholzner
Many human cells can sense the presence of exogenous DNA during infection though the cytosolic DNA receptor cyclic GMP-AMP synthase (cGAS), which produces the second messenger cyclic GMP-AMP (cGAMP). Other putative DNA receptors have been described, but whether their functions are redundant, tissue-specific or integrated in the cGAS-cGAMP pathway is unclear. Here we show that interferon-γ inducible protein 16 (IFI16) cooperates with cGAS during DNA sensing in human keratinocytes, as both cGAS and IFI16 are required for the full activation of an innate immune response to exogenous DNA and DNA viruses...
February 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/28186168/ifi16-is-required-for-dna-sensing-in-human-macrophages-by-promoting-production-and-function-of-cgamp
#4
K L Jønsson, A Laustsen, C Krapp, K A Skipper, K Thavachelvam, D Hotter, J H Egedal, M Kjolby, P Mohammadi, T Prabakaran, L K Sørensen, C Sun, S B Jensen, C K Holm, R J Lebbink, M Johannsen, M Nyegaard, J G Mikkelsen, F Kirchhoff, S R Paludan, M R Jakobsen
Innate immune activation by macrophages is an essential part of host defence against infection. Cytosolic recognition of microbial DNA in macrophages leads to induction of interferons and cytokines through activation of cyclic GMP-AMP synthase (cGAS) and stimulator of interferon genes (STING). Other host factors, including interferon-gamma inducible factor 16 (IFI16), have been proposed to contribute to immune activation by DNA. However, their relation to the cGAS-STING pathway is not clear. Here, we show that IFI16 functions in the cGAS-STING pathway on two distinct levels...
February 10, 2017: Nature Communications
https://www.readbyqxmd.com/read/28181006/cyclic-dinucleotides-in-the-scope-of-the-mammalian-immune-system
#5
Arun K Mankan, Martina Müller, Gregor Witte, Veit Hornung
First discovered in prokaryotes and more recently in eukaryotes, cyclic dinucleotides (CDNs) constitute a unique branch of second messenger signaling systems. Within prokaryotes CDNs regulate a wide array of different biological processes, whereas in the vertebrate system CDN signaling is largely dedicated to activation of the innate immune system. In this book chapter we summarize the occurrence and signaling pathways of these small-molecule second messengers, most importantly in the scope of the mammalian immune system...
February 9, 2017: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/28154575/the-analysis-of-physiological-variations-in-m2-generation-of-solanum-melongena-l-mutagenized-by-ethyl-methane-sulfonate
#6
Xiao Xi-Ou, Lin Wenqiu, Li Wei, Gao Xiaoming, Lv Lingling, Ma Feiyue, Liu Yuge
The eggplant was mutagenized with ethyl methane sulfonate (EMS) to enhance its genetic variability in our previous paper. In this article, we further analyzed the phenotype of M2 generation of mutant eggplants. A total of 325 independent M2 families were investigated for phenotypic variation. In addition to the visible phenotypic variation, chlorogenic acid (CGA) concentrations were analyzed in 26 fruits of mutants with High Performance Liquid Chromatography assay. Seventeen fruits exhibited significantly higher concentrations of CGAs than those in wild-type...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28137885/cgas-is-essential-for-the-antitumor-effect-of-immune-checkpoint-blockade
#7
Hua Wang, Shuiqing Hu, Xiang Chen, Heping Shi, Chuo Chen, Lijun Sun, Zhijian J Chen
cGMP-AMP (cGAMP) synthase (cGAS) is a cytosolic DNA sensor that activates innate immune responses. cGAS catalyzes the synthesis of cGAMP, which functions as a second messenger that binds and activates the adaptor protein STING to induce type I interferons (IFNs) and other immune modulatory molecules. Here we show that cGAS is indispensable for the antitumor effect of immune checkpoint blockade in mice. Wild-type, but not cGAS-deficient, mice exhibited slower growth of B16 melanomas in response to a PD-L1 antibody treatment...
January 30, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28132838/human-cytomegalovirus-tegument-protein-ul82-inhibits-sting-mediated-signaling-to-evade-antiviral-immunity
#8
Yu-Zhi Fu, Shan Su, Yi-Qun Gao, Pei-Pei Wang, Zhe-Fu Huang, Ming-Ming Hu, Wei-Wei Luo, Shu Li, Min-Hua Luo, Yan-Yi Wang, Hong-Bing Shu
Recognition of human cytomegalovirus (HCMV) DNA by the cytosolic sensor cGAS initiates STING-dependent innate antiviral responses. HCMV can antagonize host immune responses to promote latency infection. However, it is unknown whether and how HCMV targets the cGAS-STING axis for immune evasion. Here we identified the HCMV tegument protein UL82 as a negative regulator of STING-dependent antiviral responses. UL82 interacted with STING and impaired STING-mediated signaling via two mechanisms. UL82 inhibited the translocation of STING from the ER to perinuclear microsomes by disrupting the STING-iRhom2-TRAPβ translocation complex...
February 8, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28113112/interplay-between-hiv-1-innate-sensing-and-restriction-in-mucosal-dendritic-cells-balancing-defense-and-viral-transmission
#9
REVIEW
Nina Hertoghs, Teunis B H Geijtenbeek, Carla M S Ribeiro
Innate sensing of HIV-1 by dendritic cells (DCs) initiates cell-intrinsic signalling programs that direct virus restriction and antiviral defenses. These responses include the production of type I interferon (IFN) and a large number of IFN-stimulated genes (ISGs) with a broad spectrum of antiviral effector functions. Initial interactions of HIV-1 at the mucosal surfaces with DC-expressed innate immune factors including cGAS, TRIM5α and SAMHD1 are predictive of viraemia, inflammation and disease pathogenesis...
January 20, 2017: Current Opinion in Virology
https://www.readbyqxmd.com/read/28105693/epigenetic-regulation-of-wnt-%C3%AE-catenin-signal-associated-genes-in-gastric-neoplasia-of-the-fundic-gland-chief-cell-predominant-type
#10
Takashi Murakami, Hiroyuki Mitomi, Takashi Yao, Tsuyoshi Saito, Tomoyoshi Shibuya, Sumio Watanabe
Gastric neoplasia of the fundic gland (chief cell-predominant) type (GNCCP) is a rare variant of gastric tumor. This tumor is associated with activation of the Wnt/β-catenin signaling pathway; however, the mechanisms underlying this activation remain unknown. To elucidate potential roles of Wnt/β-catenin signal-associated gene methylation in GNCCP, we performed β-catenin immunostaining and methylation-specific polymerase chain reaction (PCR) for their associated genes, including SFRPs, APC, AXIN2, and MCC, in 26 GNCCPs [i...
January 20, 2017: Pathology International
https://www.readbyqxmd.com/read/28100608/herpes-simplex-virus-type-1-ul24-abrogates-dna-sensing-signal-pathway-by-inhibiting-nf-%C3%AE%C2%BAb-activation
#11
Haiyan Xu, Chenhe Su, Angela Pearson, Christopher H Mody, Chunfu Zheng
: Cyclic GMP-AMP synthase (cGAS) is a newly identified DNA sensor that recognizes foreign DNA, including the genome of herpes simplex virus 1 (HSV-1). Upon binding of viral DNA, cGAS produces cyclic GMP-AMP, which interacts with and activates stimulator of interferon genes (STING) to trigger the transcription of anti-viral genes such as type I interferons and production of inflammatory cytokines. HSV-1 UL24 is widely conserved among the herpesviruses family and is essential for efficient viral replication...
January 18, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28095500/senp7-potentiates-cgas-activation-by-relieving-sumo-mediated-inhibition-of-cytosolic-dna-sensing
#12
Ye Cui, Huansha Yu, Xin Zheng, Rui Peng, Qiang Wang, Yi Zhou, Rui Wang, Jiehua Wang, Bo Qu, Nan Shen, Qiang Guo, Xing Liu, Chen Wang
Cyclic GMP-AMP (cGAMP) synthase (cGAS, a.k.a. MB21D1), a cytosolic DNA sensor, catalyzes formation of the second messenger 2'3'-cGAMP that activates the stimulator of interferon genes (STING) signaling. How the cGAS activity is modulated remains largely unknown. Here, we demonstrate that sentrin/SUMO-specific protease 7 (SENP7) interacted with and potentiated cGAS activation. The small ubiquitin-like modifier (SUMO) was conjugated onto the lysine residues 335, 372 and 382 of cGAS, which suppressed its DNA-binding, oligomerization and nucleotidyl-transferase activities...
January 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28088707/dna-sensing-and-immune-responses-in-cancer-therapy
#13
REVIEW
Jian Qiao, Haidong Tang, Yang-Xin Fu
The identification of critical DNA sensors and their pathways has led to revealing the central role of DNA sensing in immune system. It has been initially demonstrated that DNA sensing and immune responses have high impacts on the development and prevention of infection and inflammatory. In addition to toll-like receptor pathways, there is now also emerging evidence that cytosolic enzyme cyclic GMP-AMP synthase (cGAS) is essential for the recognition of not only pathogen-derived DNA but also tumor DNA for innate sensing...
January 12, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28087918/-research-progress-on-the-role-of-tank-binding-kinase-1-in-anti-virus-innate-immune-response
#14
Xue Wang, Yuchuan Zhang, Wei Chen
The innate immune response against viral infection is mainly relies on type I interferon, the production of which is mediated by TANK-binding kinase 1 (TBK1). It is revealed that the downstream TBK1 is activated by viral nucleic acid sensors RIG-I, cGAS and TLR3. The activity of TBK1 is complexly and precisely regulated by different type of protein modifications, including phosphorylation, ubiquitination and Sumolylation. This article focuses on the role of TBK1 in anti-viral innate immunity and the regulatory mechanism for the TBK1 activation...
May 25, 2016: Zhejiang da Xue Xue Bao. Yi Xue Ban, Journal of Zhejiang University. Medical Sciences
https://www.readbyqxmd.com/read/28077645/herpes-simplex-virus-1-abrogates-cgas-sting-mediated-cytosolic-dna-sensing-pathway-via-its-virion-host-shutoff-protein-ul41
#15
Chenhe Su, Chunfu Zheng
: Cyclic GMP-AMP synthase (cGAS) is a key DNA sensor capable of detecting microbial DNA and activating the adaptor protein stimulator of interferon genes (STING), leading to interferon (IFN) production and host antiviral responses. Cells exhibited reduced type I IFN production in response to cytosolic DNA in the absence of cGAS. Although cGAS/STING-mediated DNA-sensing signal is crucial for host defense against many viruses, especial for DNA viruses, few viral components have been identified to specifically target this signaling pathway...
January 11, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28073693/crosstalk-between-cytoplasmic-rig-i-and-sting-sensing-pathways
#16
REVIEW
Alessandra Zevini, David Olagnier, John Hiscott
Detection of evolutionarily conserved molecules on microbial pathogens by host immune sensors represents the initial trigger of the immune response against infection. Cytosolic receptors sense viral and intracellular bacterial genomes, as well as nucleic acids produced during replication. Once activated, these sensors trigger multiple signaling cascades, converging on the production of type I interferons and proinflammatory cytokines. Although distinct classes of receptors are responsible for the RNA and DNA sensing, the downstream signaling components are physically and functionally interconnected...
January 7, 2017: Trends in Immunology
https://www.readbyqxmd.com/read/28069950/chronic-innate-immune-activation-of-tbk1-suppresses-mtorc1-activity-and-dysregulates-cellular-metabolism
#17
Maroof Hasan, Vijay K Gonugunta, Nicole Dobbs, Aktar Ali, Guillermo Palchik, Maria A Calvaruso, Ralph J DeBerardinis, Nan Yan
Three-prime repair exonuclease 1 knockout (Trex1(-/-)) mice suffer from systemic inflammation caused largely by chronic activation of the cyclic GMP-AMP synthase-stimulator of interferon genes-TANK-binding kinase-interferon regulatory factor 3 (cGAS-STING-TBK1-IRF3) signaling pathway. We showed previously that Trex1-deficient cells have reduced mammalian target of rapamycin complex 1 (mTORC1) activity, although the underlying mechanism is unclear. Here, we performed detailed metabolic analysis in Trex1(-/-) mice and cells that revealed both cellular and systemic metabolic defects, including reduced mitochondrial respiration and increased glycolysis, energy expenditure, and fat metabolism...
January 24, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28041929/the-chlamydia-trachomatis-inclusion-membrane-protein-cpos-counteracts-sting-mediated-cellular-surveillance-and-suicide-programs
#18
Barbara S Sixt, Robert J Bastidas, Ryan Finethy, Ryan M Baxter, Victoria K Carpenter, Guido Kroemer, Jörn Coers, Raphael H Valdivia
Evading cell death is critical for Chlamydia to maintain a replicative niche, but the underlying mechanisms are unknown. We screened a library of Chlamydia mutants for modulators of cell death. Inactivation of the inclusion membrane protein CpoS (Chlamydia promoter of survival) induced rapid apoptotic and necrotic death in infected cells. The protection afforded by CpoS is limited to the inclusion in which it resides, indicating that it counteracts a spatially restricted pro-death signal. CpoS-deficient Chlamydia induced an exacerbated type I interferon response that required the host cGAS/STING/TBK1/IRF3 signaling pathway...
January 11, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28031360/herpes-simplex-virus-type-1-ubiquitin-specific-protease-ul36-abrogates-nf-%C3%AE%C2%BAb-activation-in-dna-sensing-signal-pathway
#19
Ruijie Ye, Chenhe Su, Haiyan Xu, Chunfu Zheng
: The DNA sensing pathway triggers innate immune responses against DNA virus infection and the NF-κB signaling plays a critical role in establishing the innate immunity. Here we report that the herpes simplex virus type 1 (HSV-1) ubiquitin-specific protease (UL36USP), which is a deubiquitinase (DUB), antagonizes the NF-κB activation, depending on its DUB activity. In this study, ectopically expressed UL36USP blocked promoter activation of interferon (IFN)-β and NF-κB induced by cyclic GMP-AMP synthase (cGAS) and stimulator of interferon genes (STING)...
December 28, 2016: Journal of Virology
https://www.readbyqxmd.com/read/28012692/mediation-of-coffee-induced-improvements-in-human-vascular-function-by-chlorogenic-acids-and-its-metabolites-two-randomized-controlled-crossover-intervention-trials
#20
Charlotte E Mills, Andreas Flury, Cynthia Marmet, Laura Poquet, Stefano F Rimoldi, Claudio Sartori, Emrush Rexhaj, Roman Brenner, Yves Allemann, Diane Zimmermann, Glenn R Gibson, Don S Mottram, Maria-Jose Oruna-Concha, Lucas Actis-Goretta, Jeremy P E Spencer
BACKGROUND & AIMS: Polyphenol intake has been linked to improvements in human vascular function, although data on hydroxycinnamates, such as chlorogenic acid (CGA) have not yet been studied. We aimed to investigate the impact of coffee intake rich in chlorogenic acid on human vascular function and whether CGAs are involved in potential effects. METHODS: Two acute randomized, controlled, cross-over human intervention trials were conducted. The impact of coffee intake, matched for caffeine but differing in CGA content (89, and 310 mg) on flow-mediated dilatation (FMD) was assessed in 15 healthy male subjects...
November 30, 2016: Clinical Nutrition: Official Journal of the European Society of Parenteral and Enteral Nutrition
keyword
keyword
12133
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"