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https://www.readbyqxmd.com/read/28250121/porcine-deltacoronavirus-nsp5-antagonizes-type-i-interferon-signaling-by-cleaving-stat2
#1
Xinyu Zhu, Dang Wang, Junwei Zhou, Ting Pan, Jiyao Chen, Yuting Yang, Mengting Lv, Xu Ye, Guiqing Peng, Liurong Fang, Shaobo Xiao
Porcine deltacoronavirus (PDCoV) is an emerging swine enteropathogenic coronavirus. The first outbreak of PDCoV was announced from the United States in 2014, followed by reports in Asia. The nonstructural protein nsp5 is a 3C-like protease of coronavirus and our previous study showed that PDCoV nsp5 inhibits type I interferon (IFN) production. In this study, we found that PDCoV nsp5 significantly inhibited IFN-stimulated response element (ISRE) promoter activity and transcription of IFN-stimulated genes (ISGs), suggesting that PDCoV nsp5 also suppresses IFN signaling...
March 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28244869/yod1-traf6-association-balances-p62-dependent-il-1-signaling-to-nf-%C3%AE%C2%BAb
#2
Gisela Schimmack, Kenji Schorpp, Kerstin Kutzner, Torben Gehring, Jara Kerstin Brenke, Kamyar Hadian, Daniel Krappmann
The ubiquitin ligase TRAF6 is a key regulator of canonical IκB kinase (IKK)/NF-κB signaling in response to interleukin-1 (IL-1) stimulation. Here, we identified the deubiquitinating enzyme YOD1 (OTUD2) as a novel interactor of TRAF6 in human cells. YOD1 binds to the C-terminal TRAF homology domain of TRAF6 that also serves as the interaction surface for the adaptor p62/Sequestosome-1, which is required for IL-1 signaling to NF-κB. We show that YOD1 competes with p62 for TRAF6 association and abolishes the sequestration of TRAF6 to cytosolic p62 aggregates by a non-catalytic mechanism...
February 28, 2017: ELife
https://www.readbyqxmd.com/read/28202068/the-dna-damage-response-promotes-polyomavirus-jc-infection-by-nucleus-to-cytoplasm-nf-kappab-activation
#3
Martyn K White, Anna Bellizzi, Gabriele Ibba, Valeria Pietropaolo, Anna T Palamara, Hassen S Wollebo
BACKGROUND: Infection of glial cells by human neurotropic polyomavirus JC (JCV), the causative agent of the CNS demyelinating disease progressive multifocal leukoencephalopathy (PML), rapidly inflicts damage to cellular DNA. This activates DNA damage response (DDR) signaling including induction of expression of DNA repair factor Rad51. We previously reported that Rad51 co-operates with the transcription factor NF-κB p65 to activate JCV early transcription. Thus Rad51 induction by JCV infection may provide positive feedback for viral activation early in JCV infection...
February 15, 2017: Virology Journal
https://www.readbyqxmd.com/read/28192730/inducible-turnover-of-optineurin-regulates-t-cell-activation
#4
Angela Montecalvo, Simon C Watkins, Jordan Orange, Lawrence P Kane
Optineurin (Optn) is an adaptor protein with homology to NF-κB essential modulator (NEMO), the regulatory subunit of the IκB kinase (IKK) complex. Dysregulation of Optn has been linked to neurodegenerative, autoimmune and bone diseases. Optn shares a high degree of homology with NEMO, but is not part of the same high-molecular weight complex containing IKKα and IKKβ. Despite its homology with NEMO and the fact that it has been the subject of extensive study in several cell types, there are no published studies addressing the role of Optn during T cell activation...
May 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28185954/wip1-directly-dephosphorylates-nlk-and-increases-wnt-activity-during-germ-cell-development
#5
Seung-Ju Cho, Bok-Sik Cha, Ok-Seon Kwon, Jisun Lim, Dong-Myung Shin, Dong Wook Han, Tohru Ishitani, Eek-Hoon Jho, Albert J Fornace, Hyuk-Jin Cha
Mice null for wild-type p53-induced phosphatase 1 (WIP1) display defects in testis development and spermatogenesis, resulting in reduced fertility. However, the molecular mechanism underlying these abnormalities in the testis remains uncharacterized. We report that the phosphatase activity of WIP1 increases Wnt activity through Nemo-like kinase (NLK). WIP1 directly interacted with NLK, which is highly homologous to p38 MAPK, a WIP1 substrate, and dephosphorylated its activation site. The WIP1-mediated inhibition of NLK activity markedly decreased the phosphorylation of lymphoid enhancer-binding factor 1 (LEF1), enhancing its interaction with β-catenin...
April 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28095323/pattern-recognitions-receptors-in-immunodeficiency-disorders
#6
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/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/27979972/phosphorylation-by-nlk-inhibits-yap-14-3-3-interactions-and-induces-its-nuclear-localization
#8
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/27956705/arfgap-domain-containing-protein-2-adap2-integrates-upstream-and-downstream-modules-of-rig-i-signaling-and-facilitates-type-i-interferon-production
#9
Pradeep Bist, Susana Soo-Yeon Kim, Niyas Kudukil Pulloor, Kathleen McCaffrey, Sajith Kumar Nair, Yiliu Liu, Rongtuan Lin, Manoj N Krishnan
Transcription of type I interferon genes 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-interferon regulatory factor 3 (IRF3) kinase-transcription factor module. However, how the 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...
March 15, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/27929056/gsk-3%C3%AE-controls-nf-kappab-activity-via-ikk%C3%AE-nemo
#10
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/27903773/nlk-mediated-phosphorylation-of-hdac1-negatively-regulates-wnt-signaling
#11
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
#12
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/27875771/nemo-like-kinase-1-nlk1-and-paraxial-protocadherin-papc-cooperatively-control-xenopus-gastrulation-through-regulation-of-wnt-planar-cell-polarity-pcp-signaling
#13
Rahul Kumar, Anja Ciprianidis, Susanne Theiß, Herbert Steinbeißer, Lilian T Kaufmann
The Wnt/planar cell polarity (PCP) pathway directs cell migration during vertebrate gastrulation and is essential for proper embryonic development. Paraxial protocadherin (PAPC, Gene Symbol pcdh8.2) is an important activator of Wnt/PCP signaling during Xenopus gastrulation, but how PAPC activity is controlled is incompletely understood. Here we show that Nemo-like kinase 1 (Nlk1), an atypical mitogen-activated protein (MAP) kinase, physically associates with the C-terminus of PAPC. This interaction mutually stabilizes both proteins by inhibiting polyubiquitination...
October 28, 2016: Differentiation; Research in Biological Diversity
https://www.readbyqxmd.com/read/27806760/-the-crosstalk-between-canonical-and-noncanonical-wnt-signaling-pathway-in-osteoblast-differentiation-of-periodontal-ligament-stem-cells-in-inflammatory-microenvironments
#14
N Liu, H G Shi, W Zhang, B Gu
Objective: To investigate the crosstalk between canonical Wnt/β-catenin and noncanonical Wnt/Ca(2+) pathway in osteoblast differentiation process of periodontal ligament stem cell (PDLSC) in inflammatory microenvironments. Methods: PDLSCs were obtained from human healthy individuals(H-PDLSC) and patients with periodontitis(P-PDLSC). The H/P-PDLSCs were transfected with β-catenin siRNA. Cell morphology was observed under fluorescent microscope and transfection efficiency was easured by Western blotting after transfection of PDLSC...
November 9, 2016: Zhonghua Kou Qiang Yi Xue za Zhi, Zhonghua Kouqiang Yixue Zazhi, Chinese Journal of Stomatology
https://www.readbyqxmd.com/read/27777308/molecular-determinants-of-scaffold-induced-linear-ubiquitinylation-of-b-cell-lymphoma-leukemia-10-bcl10-during-t-cell-receptor-and-oncogenic-caspase-recruitment-domain-containing-protein-11-card11-signaling
#15
Yong-Kang Yang, Chao Yang, Waipan Chan, Zhaoquan Wang, Katelynn E Deibel, Joel L Pomerantz
The activation of NF-κB downstream of T cell receptor (TCR) engagement is a key signaling step required for normal lymphocyte function during the adaptive immune response. During TCR signaling, the adaptor protein Bcl10 is inducibly recruited to the CARD11 scaffold protein as part of a multicomponent complex that induces IκB kinase (IKK) activity and NF-κB activation. Here, we show that a consequence of this recruitment is the TCR-induced conjugation of Bcl10 with linear-linked polyubiquitin chains to generate the signaling intermediate Lin(Ub)n-Bcl10, which is required for the association of Bcl10 with the NEMO subunit of the IKK complex...
December 9, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27764156/nemo-like-kinase-nlk-is-a-pathological-signaling-effector-in-the-mouse-heart
#16
Ruijie Liu, Hadi Khalil, Suh-Chin J Lin, Michelle A Sargent, Allen J York, Jeffery D Molkentin
Nemo-like kinase (NLK) is an evolutionary conserved serine/threonine protein kinase implicated in development, proliferation and apoptosis regulation. Here we identified NLK as a gene product induced in the hearts of mice subjected to pressure overload or myocardial infarction injury, suggesting a potential regulatory role with pathological stimulation to this organ. To examine the potential functional consequences of increased NLK levels, cardiac-specific transgenic mice with inducible expression of this gene product were generated, as well as cardiac-specific Nlk gene-deleted mice...
2016: PloS One
https://www.readbyqxmd.com/read/27717746/brain-and-muscle-aryl-hydrocarbon-receptor-nuclear-translocator-like-protein-1-cooperates-with-glycogen-synthase-kinase-3%C3%AE-to-regulate-osteogenesis-of-bone-marrow-mesenchymal-stem-cells-in-type-2-diabetes
#17
Xiaoguang Li, Na Liu, Yizhu Wang, Jinglong Liu, Haigang Shi, Zhenzhen Qu, Tingting Du, Bin Guo, Bin Gu
Type 2 diabetes mellitus (T2DM) is associated with inhibited osteogenesis of bone marrow mesenchymal stem cells (BMSCs). Brain and muscle ARNT-like protein 1 (BMAL1) has been linked to the T2DM-related bone remodeling, however, the specific mechanism is still unclear. Herein, we aimed to determine the role of BMAL1 in T2DM-induced suppression of BMSCs osteogenesis. Inhibited osteogenesis and BMAL1 expression were showed in diabetic BMSCs. And while β-catenin and T cell factor (TCF) expression were decreased, the glycogen synthase kinase-3β (GSK-3β) and nemo-like kinase (NLK) expression were increased in diabetic BMSCs...
January 15, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/27582100/lymphocyte-specific-deletion-of-ikk2-or-nemo-mediates-increase-of-intrarenal-th17-cells-and-accelerates-renal-damage-in-ischemia-reperfusion-injury-mouse-model
#18
Linlin Guo, Hannah Heejung Lee, María de Las Mercedes Noriega, Hans-Joachim Paust, Gunther Zahner, Friedrich Thaiss
Acute kidney injury (AKI) is associated with poor patient outcome and a global burden for end-stage renal disease. Ischemia-reperfusion injury (IRI) is one of the major causes of AKI, and experimental work has revealed many details of the inflammatory response in the kidney. Here, we investigated whether deletion of the NF-κB kinases IKK2 or NEMO in lymphocytes or systemic inhibition of IKK2 would cause different kidney inflammatory responses after IRI induction. Serum creatinine, BUN level and renal tubular injury score were significantly increased in CD4creIKK2f/f (CD4xIKK2Δ) and CD4creNEMOf/f (CD4xNEMOΔ) mice compared with CD4cre mice after IRI induction...
August 31, 2016: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/27577116/impact-of-mir-208-and-its-target-gene-nemo-like-kinase-on-the-protective-effect-of-ginsenoside-rb1-in-hypoxia-ischemia-injuried-cardiomyocytes
#19
Xu Yan, Jianxun Liu, Hongjin Wu, Yuna Liu, Sidao Zheng, Chengying Zhang, Cui Yang
BACKGROUND/AIMS: Ginsenoside Rb1 (GS-Rb1) is one of the most important active pharmacological extracts of the Traditional Chinese Medicine ginseng, with extensive evidence of its cardioprotective properties. Mir-208 has been shown to act as a biomarker of acute myocardial infarction in vivo studies including man. However the impact of miR-208 on the protective effect of GS-Rb1 in hypoxia/ischemia injured cardiomyocytes remains unclear. The current study aims to investigate the target gene of miR-208 and the impact on the protective effect of GS-Rb1 in hypoxia/ischemia (H/I) injuried cardiomyocytes...
2016: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/27560715/nemo-regulates-a-cell-death-switch-in-tnf-signaling-by-inhibiting-recruitment-of-ripk3-to-the-cell-death-inducing-complex-ii
#20
Alessandra Pescatore, Elio Esposito, Peter Draber, Henning Walczak, Matilde Valeria Ursini
Incontinentia Pigmenti (IP) is a rare X-linked disease characterized by early male lethality and multiple abnormalities in heterozygous females. IP is caused by NF-κB essential modulator (NEMO) mutations. The current mechanistic model suggests that NEMO functions as a crucial component mediating the recruitment of the IκB-kinase (IKK) complex to tumor necrosis factor receptor 1 (TNF-R1), thus allowing activation of the pro-survival NF-κB response. However, recent studies have suggested that gene activation and cell death inhibition are two independent activities of NEMO...
August 25, 2016: Cell Death & Disease
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