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https://www.readbyqxmd.com/read/28820388/blockade-of-the-lrp16-pkr-nf-%C3%AE%C2%BAb-signaling-axis-sensitizes-colorectal-carcinoma-cells-to-dna-damaging-cytotoxic-therapy
#1
Xiaolei Li, Zhiqiang Wu, Xiaojing An, Qian Mei, Miaomiao Bai, Leena Hanski, Xiang Li, Tero Ahola, Weidong Han
Acquired therapeutic resistance by tumors is a substantial impediment to reducing the morbidity and mortality that are attributable to human malignancies. The mechanisms responsible for the dramatic shift between chemosensitivity and chemoresistance in colorectal carcinoma have not been defined. Here, we report that LRP16 selectively interacts and activates double-stranded RNA-dependent kinase (PKR), and also acts as scaffolds to assist the formation of a ternary complex of PKR and IKKβ, prolonging the polymers of ADP-ribose (PAR)-dependent nuclear factor kappa B (NF-κB) transactivation caused by DNA-damaging agents and confers acquired chemoresistance...
August 18, 2017: ELife
https://www.readbyqxmd.com/read/28818618/ctenopharyngodon-idella-p53-mediates-between-nf-%C3%AE%C2%BAb-and-pkr-at-the-transcriptional-level
#2
Qingli Huang, Dingkun Xie, Huiling Mao, Haizhou Wang, Zhen Wu, Keyi Huang, Yiqi Wan, Qun Xu, Chengyu Hu
p53, NF-κB and PKR are well-known to be involved in antiviral response. Although p53 has been reported in fish, its role in the regulation of NF-κB and PKR is not well understood. Here, we cloned and characterized the full length of cDNA sequence of grass carp (Ctenopharyngodon idella) p53 (Cip53) and its promoter sequence. The full length cDNA of Cip53 was 1879 bp with an ORF of 1116 bp encoding a polypeptide of 371 amino acids. Phylogenetic tree analysis revealed that Cip53 shares high homology with Dario rerio p53 (Drp53)...
August 14, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28798082/long-dsrnas-promote-an-anti-viral-response-in-pacific-oyster-hampering-ostreid-herpesvirus-1-replication
#3
Marianna Pauletto, Amélie Segarra, Caroline Montagnani, Virgile Quillien, Nicole Faury, Jacqueline Le Grand, Philippe Miner, Bruno Petton, Yannick Labreuche, Elodie Fleury, Caroline Fabioux, Luca Bargelloni, Tristan Renault, Arnaud Huvet
Double stranded RNA-mediated genetic interference (RNAi) is a widely used reverse genetic tool for determining the loss-of-function phenotype of a gene. Here, the possible induction of an immune response by long dsRNA was tested in a marine bivalve, i.e. Crassostrea gigas, as well as the specific role of the subunit 2 of the nuclear factor κB inhibitor (IκB2). This gene is a candidate of particular interest for functional investigations in the context of massive mortality oyster events as Cg-IκB2 mRNA levels exhibited significant variation depending on the amount of ostreid herpesvirus 1 (OsHV-1) DNA detected...
August 10, 2017: Journal of Experimental Biology
https://www.readbyqxmd.com/read/28796255/pdi-is-an-essential-redox-sensitive-activator-of-perk-during-the-unfolded-protein-response-upr
#4
Philip Kranz, Fabian Neumann, Alexandra Wolf, Fabian Classen, Mosche Pompsch, Tobias Ocklenburg, Jennifer Baumann, Kirsten Janke, Melanie Baumann, Kirsten Goepelt, Helena Riffkin, Eric Metzen, Ulf Brockmeier
Endoplasmic reticulum (ER) stress leads to activation of the unfolded protein response (UPR) that results in transient suppression of protein translation to allow recovery but leads to cell death when stress cannot be resolved. Central to initiation of the UPR is the activation of the ER transmembrane kinase protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK). Here we report that the thiol oxidoreductase ERp57 and protein disulfide isomerase-A1 (PDI), which belong to the same family of luminal ER oxidoreductases, have strikingly opposing roles in the regulation of PERK function...
August 10, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28794024/highly-pathogenic-new-world-arenavirus-infection-activates-the-pattern-recognition-receptor-pkr-without-attenuating-virus-replication-in-human-cells
#5
Cheng Huang, Olga A Kolokoltsova, Elizabeth J Mateer, Takaaki Koma, Slobodan Paessler
The arenavirus family consists of several highly pathogenic viruses including the Old World (OW) arenavirus Lassa fever virus (LASV) and the New World (NW) Junín virus (JUNV) and Machupo virus (MACV). Host response to infection by these pathogenic arenaviruses is distinct in many aspects. NW JUNV and MACV infections readily induce an IFN response in human cells, while OW LASV infection usually triggers an undetectable or weak IFN response. JUNV induces IFN response through RIG-I, suggesting that the host non-self RNA sensor readily detects JUNV viral RNAs during infection and activates IFN response...
August 9, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28760986/pum1-is-a-biphasic-negative-regulator-of-innate-immunity-genes-by-suppressing-lgp2
#6
Yonghong Liu, Linlin Qu, Yuanyuan Liu, Bernard Roizman, Grace Guoying Zhou
PUM1 is an RNA binding protein shown to regulate the stability and function of mRNAs bearing a specific sequence. We report the following: (i) A key function of PUM1 is that of a repressor of key innate immunity genes by repressing the expression of LGP2. Thus, between 12 and 48 hours after transfection of human cells with siPUM1 RNA there was an initial (phase 1) upsurge of transcripts encoding LGP2, CXCL10, IL6, and PKR. This was followed 24 hours later (phase 2) by a significant accumulation of mRNAs encoding RIG-I, SP100, MDA5, IFIT1, PML, STING, and IFNβ...
August 15, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28748322/schisandrin-b-ameliorates-myocardial-ischemia-reperfusion-injury-through-attenuation-of-endoplasmic-reticulum-stress-induced-apoptosis
#7
Wei Zhang, Zhiqing Sun, Fanhua Meng
Schisandrin B (Sch B), an active composition isolated from the fruit of Schisandra chinensis, has been proved to possess antiinflammatory, antioxidant and anti-endoplasmic reticulum (ER) stress effects in many rodent tissues. However, the exact mechanism of cardioprotective effect of Sch B still needs more study. Here, we detected the effects of Sch B on myocardial ischemia/reperfusion (I/R) injury rats. I/R injury model in this study was established by left anterior descending coronary artery ligation for 40 min followed by 1 h of reperfusion...
July 26, 2017: Inflammation
https://www.readbyqxmd.com/read/28740342/hepatitis-c-virus-ns5a-region-mutation-in-chronic-hepatitis-c-genotype-1-patients-who-are-non-responders-to-two-or-more-treatments-and-its-relationship-with-response-to-a-new-treatment
#8
Paloma Muñoz de Rueda, José Manuel Fuentes Rodríguez, Rosa Quiles Pérez, Ana Gila Medina, Ana Belén Martín Álvarez, Jorge Casado Ruíz, Angeles Ruíz Extremera, Javier Salmerón
AIM: To determine the number of mutations in the NS5A region of the hepatitis C virus (HCV) and its relationship to the response to antiviral therapy in patients with chronic hepatitis C genotype 1 who are non-responders to two or more treatments. METHODS: Sequences within HCV NS5A [PKR binding domain (PKRBD) and the interferon-sensitivity-determining region (ISDR)] were analysed via direct sequencing in a selected cohort of 72 patients, with a total of 201 treatments [interferon-alpha (IFN-α), n = 49; IFN-α + ribavirin (RBV), n = 75; pegylated (peg) IFN-α + RBV, n = 47; first-generation direct-acting antivirals (DAAs), n = 13; and second-generation DAAs, n = 17]...
July 7, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28738780/distinct-herpesvirus-resistances-and-immune-responses-of-three-gynogenetic-clones-of-gibel-carp-revealed-by-comprehensive-transcriptomes
#9
Fan-Xiang Gao, Yang Wang, Qi-Ya Zhang, Cheng-Yan Mou, Zhi Li, Yuan-Sheng Deng, Li Zhou, Jian-Fang Gui
BACKGROUND: Gibel carp is an important aquaculture species in China, and a herpesvirus, called as Carassius auratus herpesvirus (CaHV), has hampered the aquaculture development. Diverse gynogenetic clones of gibel carp have been identified or created, and some of them have been used as aquaculture varieties, but their resistances to herpesvirus and the underlying mechanism remain unknown. RESULTS: To reveal their susceptibility differences, we firstly performed herpesvirus challenge experiments in three gynogenetic clones of gibel carp, including the leading variety clone A(+), candidate variety clone F and wild clone H...
July 24, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28724761/isg15-modulates-type-i-interferon-signaling-and-antiviral-response-during-hepatitis-e-virus-replication
#10
Harini Sooryanarain, Adam J Rogers, Dianjun Cao, Mary Etna R Haac, Yogesh A Karpe, Xiang-Jin Meng
Hepatitis E virus (HEV), a single-stranded positive-sense RNA virus, generally causes a self-limiting acute viral hepatitis, although chronic HEV infection has recently become a significant clinical problem in immunocompromised individuals especially in solid organ transplant recipients. Innate immunity, via type-I interferon (IFN) response, plays an important role during initial stages of a viral infection. ISG15, an IFN-induced ubiquitin-like protein, is known to have an immunomodulatory role, as well as can impart a direct antiviral effect against a wide spectrum of virus families...
July 19, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28724458/clinical-and-therapeutic-potential-of-protein-kinase-pkr-in-cancer-and-metabolism
#11
M B Garcia-Ortega, G J Lopez, G Jimenez, J A Garcia-Garcia, V Conde, H Boulaiz, E Carrillo, M Perán, J A Marchal, M A Garcia
The protein kinase R (PKR, also called EIF2AK2) is an interferon-inducible double-stranded RNA protein kinase with multiple effects on cells that plays an active part in the cellular response to numerous types of stress. PKR has been extensively studied and documented for its relevance as an antiviral agent and a cell growth regulator. Recently, the role of PKR related to metabolism, inflammatory processes, cancer and neurodegenerative diseases has gained interest. In this review, we summarise and discuss the involvement of PKR in several cancer signalling pathways and the dual role that this kinase plays in cancer disease...
July 20, 2017: Expert Reviews in Molecular Medicine
https://www.readbyqxmd.com/read/28703114/inhibition-of-perk-dependent-pro-adaptive-signaling-pathway-as-a-promising-approach-for-cancer-treatment
#12
Wioletta Rozpędek, Dariusz Pytel, Łukasz Dziki, Alicja Nowak, Adam Dziki, J Alan Diehl, Ireneusz Majsterek
Endoplasmic Reticulum (ER) is an organelle that is vital for cell growth and maintenance of homeostasis. Recent studies have reported that numerous human diseases, including cancer, are strictly connected to disruption of ER homeostasis. In order to counteract adverse intracellular conditions, cancer cells induce protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK)-dependent, pro-adaptive unfolded protein response (UPR) signaling branches. If ER stress is severe or prolonged, pro-adaptive signaling networks are insufficient, resulting in apoptotic cell death of cancer cells...
June 30, 2017: Polski Przeglad Chirurgiczny
https://www.readbyqxmd.com/read/28702377/dsrna-binding-domain-of-pkr-is-proteolytically-released-by-enterovirus-a71-to-facilitate-viral-replication
#13
Yu-Hsiu Chang, Kean Seng Lau, Rei-Lin Kuo, Jim-Tong Horng
Enterovirus 71 (EV-A71) causes hand, foot and mouth disease in young children and infants, but can also cause severe neurological complications or even death. The double-stranded RNA (dsRNA)-dependent protein kinase R (PKR), an interferon-induced antiviral protein, phosphorylates the regulatory α-subunit of the eukaryotic translation initiation factor 2 in response to viral infection, thereby blocking the translation of cellular and viral mRNA and promoting apoptosis. The cleavage of PKR after infection with poliovirus, a prototype enterovirus, has been reported by others, but the underlying mechanism of this cleavage and its role in viral replication remain unclear...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28688954/rifampicin-induced-injury-in-hepg2-cells-is-alleviated-by-tudca-via-increasing-bile-acid-transporters-expression-and-enhancing-the-nrf2-mediated-adaptive-response
#14
Weiping Zhang, Lihong Chen, Hui Feng, Wei Wang, Yi Cai, Fen Qi, Xiaofang Tao, Jun Liu, Yujun Shen, Xiaofei Ren, Xi Chen, Jianming Xu, Yuxian Shen
Bile acid transporters and the nuclear factor erythroid 2-related factor (Nrf-2)-mediated adaptive response play important roles in the development of drug-induced liver injury (DILI). However, little is known about the contribution of the adaptive response to rifampicin (RFP)-induced cell injury. In this study, we found RFP decreased the survival rate of HepG2 cells and increased the levels of lactate dehydrogenase (LDH), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (AKP), γ-glutamyl-transferase (γ-GT), total bilirubin (TBIL), direct bilirubin (DBIL), indirect bilirubin (IBIL), total bile acid (TBA) and adenosine triphosphate (ATP) in the cell culture supernatants in both a concentration- and a time-dependent manner...
July 6, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28688763/protective-function-of-slc30a10-induced-via-perk-atf4-pathway-against-1-methyl-4-phenylpyridinium
#15
Suzuna Go, Hisaka Kurita, Kazuki Yokoo, Masatoshi Inden, Taiho Kambe, Isao Hozumi
Solute carrier family 30 member 10 (SLC30A10) has been known as manganese transporter. It has been suggested that neurodegenerative diseases are related with cellular stress such as oxidative stress or endoplasmic reticulum (ER) stress. However, it remains unknown whether SLC30A10 is actually involved in several intracellular stress. We found that the level of Slc30a10 was increased in midbrain of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice. Therefore, we further investigated the role of SLC30A10 in the 1-methyl-4-phenylpiridium ion (MPP(+))-induced intracellular stress, and the molecular mechanism underlying SLC30A10 induction by MPP(+) treatment...
September 2, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28683312/an-ancient-pseudoknot-in-tnf-%C3%AE-pre-mrna-activates-pkr-inducing-eif2%C3%AE-phosphorylation-that-potently-enhances-splicing
#16
Lise Sarah Namer, Farhat Osman, Yona Banai, Benoît Masquida, Rodrigo Jung, Raymond Kaempfer
Tumor necrosis factor alpha (TNF-α) is expressed promptly during inflammatory responses. Efficient TNF-α mRNA splicing is achieved through a 3' UTR element that activates RNA-dependent eIF2α protein kinase (PKR). The TNF-α RNA activator, we show, folds into a pseudoknot conserved from teleost fish to humans, critical for PKR activation and mRNA splicing. The pseudoknot constrains the RNA into two double-helical stacks having parallel axes, permitting facile PKR dimerization and trans-autophosphorylation needed for kinase activation...
July 5, 2017: Cell Reports
https://www.readbyqxmd.com/read/28673044/ctenopharyngodon-idella-ikk%C3%AE-interacts-with-pkr-and-i%C3%AE%C2%BAb%C3%AE
#17
Haizhou Wang, Qun Xu, Xiaowen Xu, Yousheng Hu, Qunhao Hou, Youlin Zhu, Chengyu Hu
Inhibitor of nuclear factor kappa-B kinase β (IKKβ) is a subunit of the IKK complex. It can activate the NF-κB pathway through phosphorylating IκB in response to a wide range of stimuli. In the present study, an IKKβ gene from grass carp (Ctenopharyngodon idella; KT282114) was cloned and identified by homologous cloning and rapid-amplification of cDNA ends (RACE) technique. The complete CiIKKβ cDNA is 3428 bp in length, with the longest open reading frame (ORF) of 2337 bp encoding a polypeptide of 778 amino acids...
August 1, 2017: Acta Biochimica et Biophysica Sinica
https://www.readbyqxmd.com/read/28665481/the-pkr-regulatory-subunit-of-pka-is-involved-in-regulating-growth-sexual-and-asexual-development-and-pathogenesis-in-fusarium-graminearum
#18
Chaoqun Li, Yonghui Zhang, Huan Wang, Lingfeng Chen, Ju Zhang, Manli Sun, Jin-Rong Xu, Chenfang Wang
Fusarium graminearum is a causal agent of the wheat scab disease and a producer of deoxynivalenol (DON) mycotoxins. Treatment with exogenous cAMP increased its DON production. To better understand the role of the cAMP-PKA pathway in F. graminearum, in this study we functionally characterized the PKR gene encoding the regulatory subunit of PKA. Mutants deleted of PKR were viable but had severe defects in growth, conidiation, and plant infection. The pkr mutant produced compact colonies with shorter aerial hyphae that were increased in the number of nuclei in hyphal compartments...
June 30, 2017: Molecular Plant Pathology
https://www.readbyqxmd.com/read/28662438/foot-and-mouth-disease-virus-induces-lysosomal-degradation-of-host-protein-kinase-pkr-by-3c-proteinase-to-facilitate-virus-replication
#19
Chuntian Li, Zixiang Zhu, Xiaoli Du, Weijun Cao, Fan Yang, Xiangle Zhang, Huanhuan Feng, Dan Li, Keshan Zhang, Xiangtao Liu, Haixue Zheng
The interferon-induced double-strand RNA activated protein kinase (PKR) plays important roles in host defense against viral infection. Here we demonstrate the significant antiviral role of PKR against foot-and-mouth disease virus (FMDV) and report that FMDV infection inhibits PKR expression and activation in porcine kidney (PK-15) cells. The viral nonstructural protein 3C proteinase (3C(pro)) is identified to be responsible for this inhibition. However, it is independent of the well-known proteinase activity of 3C(pro) or 3C(pro)-induced shutoff of host protein synthesis...
September 2017: Virology
https://www.readbyqxmd.com/read/28648883/molecular-cloning-and-functional-analysis-of-tumor-necrosis-factor-receptor-associated-factor-6-traf6-in-crossastrea-gigas
#20
Fan Mao, Jun Li, Yuehuan Zhang, Zhiming Xiang, Yang Zhang, Ziniu Yu
Tumor necrosis factor receptor-associated factor 6 (TRAF6) has been demonstrated to be a key signaling molecule involved in adaptive and innate immunity. In this study, we obtained the full length CgTRAF6 cDNA and analyzed the characteristics of the ORF and the peptide sequence in Crassostrea gigas. The deduced protein sequence of CgTRAF6 includes a conserved C-terminal TRAF domain following the RING and the zinc finger domain. The TRAF domain is composed of coiled-coil TRAF-N and MATH (meprin and TRAF-C homology) subdomains...
June 23, 2017: Fish & Shellfish Immunology
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