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https://www.readbyqxmd.com/read/28095323/pattern-recognitions-receptors-in-immunodeficiency-disorders
#1
Esameil Mortaz, Ian M Adcock, Payam Tabarsi, Ilad Alavi Darazam, Masoud Movassaghi, Johan Garssen, Hamidreza Jamaati, Aliakbar Velayati
Pattern recognition receptors (PRRs) recognize common microbial or host-derived macromolecules and have important roles in early activation and response of the immune system. Initiation of the innate immune response starts with the recognition of microbial structures called pathogen associated molecular patterns (PAMPs). Recognition of PAMPs is performed by germline-encoded receptors expressed mainly on immune cells termed pattern recognition receptors (PRRs). Several classes of pattern recognition receptors (PRRs) are involved in the pathogenesis of diseases, including Toll-like receptors (TLRs), C-type lectin receptors (CLRs), and Nod-like receptors (NLRs)...
January 14, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28052234/exploring-polyubiquitin-as-a-flexible-multiple-ligand-binding-platform
#2
David Fushman
Linear (head-to-tail linked) polyubiquitin chains play a key role in the regulation of NF-κB signaling. In this issue of Structure, Lin et al. (2017) shed light on how linear tri-ubiquitin binds to ABIN2, a molecule that shares ubiquitin-binding properties of NEMO, the key activator of NF-κB.
January 3, 2017: Structure
https://www.readbyqxmd.com/read/28035815/binding-site-configurations-probe-the-structure-and-dynamics-of-the-zinc-finger-of-nemo-nf-%C3%AE%C2%BAb-essential-modulator
#3
Ryan C Godwin, Ryan L Melvin, William H Gmeiner, Freddie R Salsbury
Zinc-finger proteins are regulators of critical signaling pathways for various cellular functions, including apoptosis and oncogenesis. Here, we investigate how binding site protonation states and zinc coordination influence protein structure, dynamics, and ultimately function, as these pivotal regulatory proteins are increasingly important for protein engineering and therapeutic discovery. To better understand the thermodynamics and dynamics of the zinc finger of NEMO (NF-κB essential modulator), as well as the role of zinc, we present results of 20 μs molecular dynamics trajectories, 5 μs for each of four active site configurations...
January 13, 2017: Biochemistry
https://www.readbyqxmd.com/read/28035784/enhancing-the-cell-permeability-and-metabolic-stability-of-peptidyl-drugs-by-reversible-bicyclization
#4
Ziqing Qian, Curran A Rhodes, Lucas C McCroskey, Jin Wen, George Appiah-Kubi, David J Wang, Denis C Guttridge, Dehua Pei
Therapeutic applications of peptides are currently limited by their proteolytic instability and impermeability to the cell membrane. A general, reversible bicyclization strategy is now reported to increase both the proteolytic stability and cell permeability of peptidyl drugs. A peptide drug is fused with a short cell-penetrating motif and converted into a conformationally constrained bicyclic structure through the formation of a pair of disulfide bonds. The resulting bicyclic peptide has greatly enhanced proteolytic stability as well as cell-permeability...
December 30, 2016: Angewandte Chemie
https://www.readbyqxmd.com/read/28034494/fighting-nemo-effect-of-17%C3%AE-ethinylestradiol-ee2-on-aggressive-behavior-and-social-hierarchy-of-the-false-clown-anemonefish-amphiprion-ocellaris
#5
Te-Hao Chen, Chun-Yu Hsieh
Aggressive behavior is crucial for maintaining social hierarchy in anemonefish. Endocrine disrupting chemicals such as EE2 may affect fish social hierarchy via disrupting their aggression. In this study, we aimed to characterize the effects of 17α-ethinylestradiol (EE2) on aggressive behavior and social hierarchy in the false clown anemonefish (Amphiprion ocellaris). In the laboratory experiment, juvenile anemonefish were randomly distributed to separated tanks to form small colonies of three individuals and were fed with EE2-dosed diet (100ng/g food) or a control diet for 90d...
December 26, 2016: Marine Pollution Bulletin
https://www.readbyqxmd.com/read/28011329/functional-role-of-ccl5-rantes-for-hcc-progression-during-chronic-liver-disease
#6
Antje Mohs, Nadine Kuttkat, Johanna Reißing, Henning Wolfgang Zimmermann, Roland Sonntag, Amanda Proudfoot, Sameh A Youssef, Alain de Bruin, Francisco Javier Cubero, Christian Trautwein
BACKGROUND & AIMS: During liver inflammation, triggering fibrogenesis and carcinogenesis immune cells play a pivotal role. In the present study we investigated the role of CCL5 in human and in murine models of chronic liver inflammation leading to HCC development. METHODS: CCL5 expression and its receptors were studied in well-defined patients with chronic liver disease (CLD) and in two murine inflammation based HCC models. The role of CCL5 in inflammation, fibrosis, tumor initiation and progression was analyzed in different cell populations of NEMO(Δhepa)/CCL5(-/-) animals and after bone marrow transplantation (BMT)...
December 20, 2016: Journal of Hepatology
https://www.readbyqxmd.com/read/28003306/microrna-221-enhances-mycn-via-targeting-nemo-like-kinase-and-functions-as-an-oncogene-related-to-poor-prognosis-in-neuroblastoma
#7
Xiao-Yan He, Zheng-Lan Tan, Qin Mou, Fang-Jie Liu, Shan Liu, Chao-Wen Yu, Jin Zhu, Lin-Ya Lv, Jun Zhang, Shan Wang, Liming Bao, Bin Peng, Hui Zhao, Lin Zou
PURPOSE: MYCN is one of the most well-characterized genetic markers of neuroblastoma (NB). However, the mechanisms as to how MYCN mediate NB tumorigenesis is not fully clear. Increasing evidence has confirmed that the dysregulation of miRNAs is involved in MYCN-mediated NB tumorigenesis, supporting their potential as therapeutic targets for NB. Though miR-221 has been reported as one of the upregulated miRNAs, the interplay between miR-221 and MYCN-mediated NB progression remains largely elusive...
December 21, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27984784/porcine-deltacoronavirus-nsp5-inhibits-interferon-%C3%AE-production-through-the-cleavage-of-nemo
#8
Xinyu Zhu, Liurong Fang, Dang Wang, Yuting Yang, Jiyao Chen, Xu Ye, Mohamed Frahat Foda, Shaobo Xiao
Porcine deltacoronavirus (PDCoV) causes acute enteric disease and mortality in seronegative neonatal piglets. Previously we have demonstrated that PDCoV infection suppresses the production of interferon-beta (IFN-β), while the detailed mechanisms are poorly understood. Here, we demonstrate that nonstructural protein 5 (nsp5) of PDCoV, the 3C-like protease, significantly inhibits Sendai virus (SEV)-induced IFN-β production by targeting the NF-κB essential modulator (NEMO), confirmed by the diminished function of NEMO cleaved by PDCoV...
December 13, 2016: Virology
https://www.readbyqxmd.com/read/27979976/yap-needs-nemo-to-guide-a-hippo
#9
Alexander Hergovich
No abstract text is available yet for this article.
January 2017: EMBO Reports
https://www.readbyqxmd.com/read/27979972/phosphorylation-by-nlk-inhibits-yap-14-3-3-interactions-and-induces-its-nuclear-localization
#10
Sungho Moon, Wantae Kim, Soyoung Kim, Youngeun Kim, Yonghee Song, Oleksii Bilousov, Jiyoung Kim, Taebok Lee, Boksik Cha, Minseong Kim, Hanjun Kim, Vladimir L Katanaev, Eek-Hoon Jho
Hippo signaling controls organ size by regulating cell proliferation and apoptosis. Yes-associated protein (YAP) is a key downstream effector of Hippo signaling, and LATS-mediated phosphorylation of YAP at Ser127 inhibits its nuclear localization and transcriptional activity. Here, we report that Nemo-like kinase (NLK) phosphorylates YAP at Ser128 both in vitro and in vivo, which blocks interaction with 14-3-3 and enhances its nuclear localization. Depletion of NLK increases YAP phosphorylation at Ser127 and reduces YAP-mediated reporter activity...
January 2017: EMBO Reports
https://www.readbyqxmd.com/read/27975995/preliminary-results-on-basil-grown-in-the-nemo-s-garden%C3%A2
#11
L Pistelli, G Flamini, R Ascrizzi, L Pistelli, C Giuliani, C Cervelli, B Ruffoni, E Princi, S Gamberini, L Gamberini, G Fontanesi
No abstract text is available yet for this article.
December 2016: Planta Medica
https://www.readbyqxmd.com/read/27956761/nemo-binding-domain-peptide-attenuates-lipopolysaccharide-induced-acute-lung-injury-by-inhibiting-the-nf-%C3%AE%C2%BAb-signaling-pathway
#12
Jianhua Huang, Li Li, Weifeng Yuan, Linxin Zheng, Zhenhui Guo, Wenjie Huang
The aim of the present study is to investigate the protective effects and relevant mechanisms exerted by NEMO-binding domain peptide (NBD) against lipopolysaccharide- (LPS-) induced acute lung injury (ALI) in mice. The ALI model was induced by intratracheally administered atomized LPS (5 mg/kg) to BABL/c mice. Half an hour before LPS administration, we treated the mice with increasing concentrations of intratracheally administered NBD or saline aerosol. Two hours after LPS administration, each group of mice was sacrificed...
2016: Mediators of Inflammation
https://www.readbyqxmd.com/read/27956705/arfgap-domain-containing-protein-2-adap2-integrates-upstream-and-downstream-modules-of-rig-i-signaling-and-facilitates-type-i-interferon-production
#13
Pradeep Bist, Soo Yeon Kim, Niyas Kudukil Pulloor, Kathleen McCaffrey, Sajith Kumar Nair, Yiliu Liu, Rongtuan Lin, Manoj N Krishnan
: Transcription of Type I interferon during RNA virus infection requires signal communication between several Pattern recognition receptor (PRR)-adaptor complexes located at distinct subcellular membranous compartments and a central cytoplasmic TBK1-IRF3 kinase-transcription factor module. However, how cell integrates signal transduction through spatially distinct modules of antiviral signaling pathways is less defined. RIG-I is a major cytosolic PRR involved in the control of several RNA viruses...
December 12, 2016: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/27929056/gsk-3%C3%AE-controls-nf-kappab-activity-via-ikk%C3%AE-nemo
#14
Senad Medunjanin, Lisa Schleithoff, Christian Fiegehenn, Soenke Weinert, Werner Zuschratter, Ruediger C Braun-Dullaeus
The NF-κB signaling pathway is central for the innate immune response and its deregulation is found in multiple disorders such as autoimmune, chronic inflammatory and metabolic diseases. IKKγ/NEMO is essential for NF-κB activation and NEMO dysfunction in humans has been linked to so-called progeria syndromes, which are characterized by advanced ageing due to age-dependent inflammatory diseases. It has been suggested that glycogen synthase kinase-3β (GSK-3β) participates in NF-κB regulation but the exact mechanism remained incompletely understood...
December 8, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27911943/enhanced-in-planta-fitness-through-adaptive-mutations-in-efpr-a-dual-regulator-of-virulence-and-metabolic-functions-in-the-plant-pathogen-ralstonia-solanacearum
#15
Anthony Perrier, Rémi Peyraud, David Rengel, Xavier Barlet, Emmanuel Lucasson, Jérôme Gouzy, Nemo Peeters, Stéphane Genin, Alice Guidot
Experimental evolution of the plant pathogen Ralstonia solanacearum, where bacteria were maintained on plant lineages for more than 300 generations, revealed that several independent single mutations in the efpR gene from populations propagated on beans were associated with fitness gain on bean. In the present work, novel allelic efpR variants were isolated from populations propagated on other plant species, thus suggesting that mutations in efpR were not solely associated to a fitness gain on bean, but also on additional hosts...
December 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27903798/lubac-modulates-lmp1-activation-of-nf%C3%AE%C2%BAb-and-irf7
#16
Ling Wang, Yujia Wang, Juan Zhao, Junping Ren, Kenton H Hall, Jonathan P Moorman, Zhi Q Yao, Shunbin Ning
: Recently, Linear Ubiquitin Assembly Complex (LUBAC)-mediated linear ubiquitination has come into focus due to its emerging role in activation of NFκB in different biological contexts. However, the role of LUBAC in LMP1 signaling leading to NFκB and IRF7 activation has not been investigated. We have shown here that RNF31, the key component of LUBAC complex, interacts with LMP1 and IRF7 in EBV-transformed cells, and that LUBAC stimualtes linear ubiquitination of NEMO and IRF7. Consequently, LUBAC is required for LMP1 signaling to full activation of NFκB, but inhibits LMP1-stimulated IRF7 transcriptional activity...
November 30, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27903773/nlk-mediated-phosphorylation-of-hdac1-negatively-regulates-wnt-signaling
#17
Katarzyna Chmielarska Masoumi, Renée Daams, Wondossen Sime, Valentina Siino, Hengning Ke, Fredrik Levander, Ramin Massoumi
The Wnt signaling pathway is essential in regulating various cellular processes. Different mechanisms of inhibition for Wnt signaling have been proposed. Besides β-catenin degradation through the proteasome, nemo-like kinase (NLK) is another molecule that is known to negatively regulate Wnt signaling. However, the mechanism by which NLK mediates the inhibition of Wnt signaling was not known. In the present study, we used primary embryonic fibroblast cells isolated from NLK-deficient mice and showed that these cells proliferate faster and have a shorter cell cycle than wild-type cells...
January 15, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/27895463/lentivirus-mediated-knockdown-of-nlk-inhibits-small-cell-lung-cancer-growth-and-metastasis
#18
Mutian Lv, Yaming Li, Xin Tian, Shundong Dai, Jing Sun, Guojiang Jin, Shenyi Jiang
Nemo-like kinase (NLK), an evolutionarily conserved serine/threonine kinase, has been recognized as a critical regulator of various cancers. In this study, we investigated the role of NLK in human small-cell lung cancer (SCLC), which is the most aggressive form of lung cancer. NLK expression was evaluated by quantitative real-time polymerase chain reaction in 20 paired fresh SCLC tissue samples and found to be noticeably elevated in tumor tissues. Lentivirus-mediated RNAi efficiently suppressed NLK expression in NCI-H446 cells, resulting in a significant reduction in cell viability and proliferation in vitro...
2016: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/27893701/the-signaling-adaptor-traf1-negatively-regulates-toll-like-receptor-signaling-and-this-underlies-its-role-in-rheumatic-disease
#19
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...
January 2017: Nature Immunology
https://www.readbyqxmd.com/read/27881655/porcine-reproductive-and-respiratory-syndrome-virus-nsp1%C3%AE-inhibits-nf-%C3%AE%C2%BAb-activation-by-targeting-the-linear-ubiquitin-chain-assembly-complex
#20
Huiyuan Jing, Liurong Fang, Zhen Ding, Dang Wang, Wenqi Hao, Li Gao, Wenting Ke, Huanchun Chen, Shaobo Xiao
: Linear ubiquitination, a newly discovered posttranslational modification, is catalyzed by the linear ubiquitin chain assembly complex (LUBAC), which is composed of three subunits: one catalytic subunit HOIP and two accessory molecules, HOIL-1L and SHARPIN. Accumulating evidence suggests that linear ubiquitination plays a crucial role in innate immune signaling and especially in the activation of the NF-κB pathway by conjugating linear polyubiquitin chains to NF-κB essential modulator (NEMO, also called IKKγ), the regulatory subunit of the IKK complex...
February 1, 2017: Journal of Virology
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