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https://www.readbyqxmd.com/read/29233925/a20-regulates-the-dna-damage-response-and-mediates-tumor-cell-resistance-to-dna-damaging-therapy
#1
Chuanzhen Yang, Weicheng Zang, Zefang Tang, Yapeng Ji, Ruidan Xu, Yongfeng Yang, Aiping Luo, Bin Hu, Zemin Zhang, Zhihua Liu, Xiaofeng Zheng
A competent DNA damage response (DDR) helps prevent cancer, but once cancer has arisen DDR can blunt the efficacy of chemotherapy and radiotherapy which cause lethal DNA breakage in cancer cells. Thus, blocking DDR may improve the efficacy of these modalities. Here we report a new DDR mechanism that interfaces with inflammatory signaling and might be blocked to improve anticancer outcomes. Specifically, we report that the ubiquitin-editing enzyme A20 binds and inhibits the E3 ubiquitin ligase RNF168, which is responsible for regulating histone H2A turnover critical for proper DNA repair...
December 12, 2017: Cancer Research
https://www.readbyqxmd.com/read/29212706/phosphorylation-of-the-e3-ubiquitin-protein-ligase-itch-diminishes-binding-to-its-cognate-e2-ubiquitin-ligase
#2
Jessica M Perex, Tsan S Xiao, Derek W Abbott
Heightened and extended inflammation underlies the pathogenesis of many disorders, including inflammatory bowel disease, sepsis, and inflammatory arthritis. Ubiquitin networks help dictate the strength and duration of inflammatory signaling. In innate immunity, the itchy E3 ubiquitin protein ligase (ITCH-)-A20 ubiquitin--editing complex inhibits receptor-interacting Ser/Thr kinase (RIPK) activation by removing K63-Lys-63-linked polyubiquitinated chains from key proteins in the nuclear factor kappa B (NF-κB) signaling pathway...
December 6, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29203883/abin-1-regulates-ripk1-activation-by-linking-met1-ubiquitylation-with-lys63-deubiquitylation-in-tnf-rsc
#3
Slawomir A Dziedzic, Zhenyi Su, Vica Jean Barrett, Ayaz Najafov, Adnan K Mookhtiar, Palak Amin, Heling Pan, Li Sun, Hong Zhu, Averil Ma, Derek W Abbott, Junying Yuan
Ubiquitylation of the TNFR1 signalling complex (TNF-RSC) controls the activation of RIPK1, a kinase critically involved in mediating multiple TNFα-activated deleterious events. However, the molecular mechanism that coordinates different types of ubiquitylation modification to regulate the activation of RIPK1 kinase remains unclear. Here, we show that ABIN-1/NAF-1, a ubiquitin-binding protein, is recruited rapidly into TNF-RSC in a manner dependent on the Met1-ubiquitylating complex LUBAC to regulate the recruitment of A20 to control Lys63 deubiquitylation of RIPK1...
December 4, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/29202455/a-simple-clinically-relevant-therapeutic-vaccine-shows-long-term-protection-in-an-aggressive-delayed-treatment-b-lymphoma-model
#4
Pallab Pradhan, Jardin Leleux, Jiaying Liu, Krishnendu Roy
Despite initial remission after successful treatments, B lymphoma patients often encounter relapses and resistance causing high mortality. Thus, there is a need to develop therapies that prevent relapse by providing long-term protection and, ultimately, lead to functional cure. In this study, our goal was to develop a simple, clinically relevant, and easily translatable therapeutic vaccine that provides durable immune protection against aggressive B cell lymphoma and identify critical immune biomarkers that are predictive of long-term survival...
November 16, 2017: JCI Insight
https://www.readbyqxmd.com/read/29202196/effects-of-dlc1-deficiency-on-endothelial-cell-contact-growth-inhibition-and-angiosarcoma-progression
#5
David Sánchez-Martín, Atsushi Otsuka, Kenji Kabashima, Taekyu Ha, Dunrui Wang, Xiaolan Qian, Douglas R Lowy, Giovanna Tosato
Background: Deleted in Liver Cancer 1 (DLC1) is a tumor suppressor gene frequently deleted in cancer. However, DLC1 is not known to be deleted in angiosarcoma, an aggressive malignancy of endothelial cell derivation. Additionally, the physiologic functions of DLC1 protein in endothelial cells are poorly defined. Methods: We investigated the effects of shRNA-induced DLC1 depletion in endothelial cells. Cell growth was measured by 3H thymidine incorporation, IncuCyte imaging, and population doublings; cell death by cell cycle analysis; gene expression by Affimetrix arrays and quantitative polymerase chain reaction; NF-κB activity by reporter assays; and protein levels by immunoblotting and immunofluorescence staining...
November 30, 2017: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/29194659/a-stress-associated-protein-atsap13-from-arabidopsis-thaliana-provides-tolerance-to-multiple-abiotic-stresses
#6
Anirudha Dixit, Parul Tomar, Evan Vaine, Hesham Abdullah, Samuel Hazen, Om Parkash Dhankher
Members of Stress Associated Protein (SAP) family in plants have been shown to impart tolerance to multiple abiotic stresses, however, their mode of action in providing tolerance to multiple abiotic stresses is largely unknown. There are 14 SAP genes in Arabidopsis thaliana containing A20, AN1, and Cys2-His2 zinc finger domains. AtSAP13, a member of the SAP family, carries two AN1 zinc finger domains and an additional Cys2-His2 domain. AtSAP13 transcripts showed upregulation in response to Cd, ABA and salt stresses...
November 30, 2017: Plant, Cell & Environment
https://www.readbyqxmd.com/read/29191940/loss-of-cellular-flice-inhibitory-protein-promotes-acute-cholestatic-liver-injury-and-inflammation-from-bile-duct-ligation
#7
Nadine Gehrke, Michael Nagel, Beate Katharina Straub, Marcus A Wörns, Marcus Schuchmann, Peter R Galle, Jörn M Schattenberg
BACKGROUND: Cholestatic liver injury results from impaired bile flow or metabolism and promotes hepatic inflammation and fibrogenesis. Toxic bile acids that accumulate in cholestasis induce apoptosis and contribute to early cholestatic liver injury, which is amplified by accompanying inflammation. Aim of the current study was to evaluate the role of the anti-apoptotic caspase 8-homologue cellular FLICE-inhibitory (cFLIP) protein during acute cholestatic liver injury. METHODS: Transgenic mice exhibiting hepatocyte-specific deletion of cFLIP (cFLIP-/-) were utilized for in vivo and in vitro analysis of cholestatic liver injury using bile duct ligation (BDL) and the addition of bile acids ex vivo...
November 30, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/29190981/a20-enhances-the-radiosensitivity-of-hepatocellular-carcinoma-cells-to-60co-%C3%AE-ionizing-radiation
#8
Rui Liu, Dongli Zhao, Xiaozhi Zhang, Suxia Han, Yunyi Yang, Jinlu Ma, Du Meng
The radioresistance of hepatocellular carcinoma (HCC) cells is a critical obstacle for effectively applying radiotherapy (RT) in HCC treatment. NF-κB, an important transcription factor, can influence critical cell fate decisions by promoting cell survival or anti-apoptosis in response to cell-stress, e.g. chemotherapies or ionizing radiation (IR). A20, also named as tumor necrosis factor α induced protein 3 (TNFAIP3), is a dominant negative regulator of NF-κB pathway and its functions in HCC are largely unknown...
November 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/29188749/bleeding-during-veno-venous-ecmo-cannot-reliably-be-predicted-by-rotational-thrombelastometry-rotem%C3%A2
#9
Christina Hellmann, Axel Schmutz, Johannes Kalbhenn
INTRODUCTION: Veno-venous extracorporeal membrane oxygenation (vvECMO) used for respiratory support is associated with clinical bleeding in at least one third of patients. Mechanisms promoting bleeding, like acquired von Willebrand syndrome, cannot be identified by routine coagulation tests. This study was performed to evaluate rotational Thrombelastography (ROTEM™) for specific results predicting bleeding events during vvECMO. METHODS: Five hundred and thirty-four ROTEM™ analyses of 57 patients over 574 days have been evaluated...
November 1, 2017: Perfusion
https://www.readbyqxmd.com/read/29179211/molecular-mechanism-of-mir-136-5p-targeting-nf-%C3%AE%C2%BAb-a20-in-the-il-17-mediated-inflammatory-response-after-spinal-cord-injury
#10
Jichen He, Jinmin Zhao, Xiaoming Peng, Xiongzhi Shi, Shaohui Zong, Gaofeng Zeng
BACKGROUND/AIMS: The pathophysiology of spinal cord injury (SCI) results in serious damage to the human body via an increase in the secondary biological processes imposed by activated astrocytes. Abnormal expression of microRNAs after SCI has become a potential research focus. However, the underlying mechanisms are poorly understood. METHODS: SCI models were established in rats using Allen's method, and the BBB scoring method was employed to assess locomotor function...
November 28, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29175599/multimodal-imaging-for-a-theranostic-approach-in-a-murine-model-of-b-cell-lymphoma-with-engineered-nanoparticles
#11
Enza Torino, Luigi Auletta, Donatella Vecchione, Francesca Maria Orlandella, Giuliana Salvatore, Enrico Iaccino, Dario Fiorenza, Annamaria Grimaldi, Annamaria Sandomenico, Sandra Albanese, Daniela Sarnataro, Matteo Gramanzini, Camillo Palmieri, Giuseppe Scala, Ileana Quinto, Paolo Netti, Marco Salvatore, Adelaide Greco
Nanoparticles (NPs) are a promising tool for in vivo multimodality imaging and theranostic applications. Hyaluronic acid (HA)-based NPs have numerous active groups that make them ideal as tumor-targeted carriers. The B-lymphoma neoplastic cells express on their surfaces a clone-specific immunoglobulin receptor (Ig-BCR). The peptide A20-36 (pA20-36) selectively binds to the Ig-BCR of A20 lymphoma cells. In this work, we demonstrated the ability of core-shell chitosan-HA-NPs decorated with pA20-36 to specifically target A20 cells and reduce the tumor burden in a murine xenograft model...
November 22, 2017: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/29175508/tnf%C3%AE-induces-tolerant-production-of-cxc-chemokines-in-colorectal-cancer-hct116-cells-via-a20-inhibition-of-erk-signaling
#12
Xin Zhou, Dongjian An, Xueting Liu, Manli Jiang, Chuang Yuan, Jinyue Hu
Ubiquitin editing enzyme A20 functions as a tumor suppressor in various cancer. However, the mechanism for A20 regulation of cancer progress is not fully understood. In this study, we found that in human colorectal cancer HCT116 cells, TNFα induced a tolerant production of CXC chemokines, including CXCL1, 2, and 8 in a dose and time dependent manner. TNFα pre-treatment of HCT116 cells down-regulated the chemokine production induced by TNFα re-treatment. TNFα induced the phosphorylation of MAPKs ERK, JNK, P38 and NF-κB P65, but only ERK inhibition decreased TNFα-induced chemokine production...
November 23, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/29173772/clinical-characteristics-and-sequence-complexity-of-anaplastic-lymphoma-kinase-gene-fusions-in-chinese-lung-cancer-patients
#13
Hong-Xia Tian, Xu-Chao Zhang, Jin-Ji Yang, Wei-Bang Guo, Zhi-Hong Chen, Zhen Wang, Yi-Long Wu
OBJECTIVES: To investigate the clinical characteristics of anaplastic lymphoma kinase (ALK) rearrangements and sequence complexity of the ALK fusion gene in Chinese lung cancer patients. METHODS: We prospectively screened ALK rearrangements in 1474 lung cancer specimens, including 1387 cases of non-small cell lung cancer (NSCLC), 54 cases of small cell lung cancer (SCLC), and 33 cases of cancer with lung metastasis from other organs by both standard polymerase chain reaction (PCR) and rapid amplification of cDNA ends (RACE)-coupled PCR...
December 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/29162874/information-processing-in-the-nf-%C3%AE%C2%BAb-pathway
#14
Karolina Tudelska, Joanna Markiewicz, Marek Kochańczyk, Maciej Czerkies, Wiktor Prus, Zbigniew Korwek, Ali Abdi, Sławomir Błoński, Bogdan Kaźmierczak, Tomasz Lipniacki
The NF-κB pathway is known to transmit merely 1 bit of information about stimulus level. We combined experimentation with mathematical modeling to elucidate how information about TNF concentration is turned into a binary decision. Using Kolmogorov-Smirnov distance, we quantified the cell's ability to discern 8 TNF concentrations at each step of the NF-κB pathway, to find that input discernibility decreases as signal propagates along the pathway. Discernibility of low TNF concentrations is restricted by noise at the TNF receptor level, whereas discernibility of high TNF concentrations it is restricted by saturation/depletion of downstream signaling components...
November 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29154209/external-signals-regulate-germinal-center-fate-determining-transcription-factors-in-the-a20-lymphoma-cell-line
#15
Juan Feng, Xin Liu, Xingya Ni, Hai Qi
Due to the apoptosis-prone nature of primary germinal center B (GCB) cells, it remains a huge challenge to dissect signals that guide their differentiation towards memory B cells and plasma cells in vitro. Here we show that the murine lymphoma cell line A20 resembles primary GCB cells in expression of GC-specific surface markers and the master transcription factor BCL6 and may serve as a useful system to model certain GCB cell behaviors in vitro. Using these cells, we found that both CD40 and B cell receptor (BCR) signaling are able to drive BCL6 downregulation, which is a prerequisite of post-GC B-cell differentiation...
November 16, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/29144391/antimicrobial-peptide-epinecidin-1-modulates-myd88-protein-levels-via-the-proteasome-degradation-pathway
#16
Bor-Chyuan Su, Jyh-Yih Chen
The cationic antimicrobial peptide epinecidin-1 was identified from Epinephelus coioides and possesses multiple biological functions, including antibacterial, antifungal, anti-tumor, and immunomodulatory effects. In addition, epinecidin-1 suppresses lipopolysaccharide (LPS)-induced inflammation by neutralizing LPS and ameliorating LPS/Toll-like receptor (TLR)-4 internalization. However, it is unclear whether the actions of epinecidin-1 depend on the regulation of TLR adaptor protein MyD88 or endogenous TLR signaling antagonists, which include A20, interleukin-1 receptor associated kinase (IRAK)-M, and suppressor of cytokine signaling (SOCS)-1...
November 16, 2017: Marine Drugs
https://www.readbyqxmd.com/read/29143862/a20-prevents-obesity-induced-development-of-cardiac-dysfunction
#17
Wenjing Xu, Cheng Wang, Minglu Liang, Long Chen, Qin Fu, Fengxiao Zhang, Yan Wang, Dan Huang, Kai Huang
Obesity and an increased free fatty acid (FFA) level are tightly linked, leading to aberrant oxidative stress, inflammation, apoptosis, and progression to cardiovascular disorders. A20 is a ubiquitin-modifying enzyme that plays a significant role in the negative regulation of inflammatory response. Here, we study the role of A20 in obesity-induced heart injury and explore the underlying mechanisms. A20 expression was first increased in mouse hearts after 4 weeks of a high-fat diet (HFD) and then was gradually decreased in the following 20 weeks...
November 16, 2017: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/29129932/the-vaccinia-virus-dna-polymerase-structure-provides-insights-into-the-mode-of-processivity-factor-binding
#18
Nicolas Tarbouriech, Corinne Ducournau, Stephanie Hutin, Philippe J Mas, Petr Man, Eric Forest, Darren J Hart, Christophe N Peyrefitte, Wim P Burmeister, Frédéric Iseni
Vaccinia virus (VACV), the prototype member of the Poxviridae, replicates in the cytoplasm of an infected cell. The catalytic subunit of the DNA polymerase E9 binds the heterodimeric processivity factor A20/D4 to form the functional polymerase holoenzyme. Here we present the crystal structure of full-length E9 at 2.7 Å resolution that permits identification of important poxvirus-specific structural insertions. One insertion in the palm domain interacts with C-terminal residues of A20 and thus serves as the processivity factor-binding site...
November 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/29125463/pharmacological-augmentation-of-nicotinamide-phosphoribosyltransferase-nampt-protects-against-paclitaxel-induced-peripheral-neuropathy
#19
Peter M LoCoco, April L Risinger, Hudson R Smith, Teresa S Chavera, Kelly A Berg, William P Clarke
Chemotherapy-induced peripheral neuropathy (CIPN) arises from collateral damage to peripheral afferent sensory neurons by anticancer pharmacotherapy, leading to debilitating neuropathic pain. No effective treatment for CIPN exists, short of dose-reduction which worsens cancer prognosis. Here we report that stimulation of nicotinamide phosphoribosyltransferase (NAMPT) produced robust neuroprotection in an aggressive CIPN model utilizing the frontline anticancer drug, paclitaxel (PTX). Daily treatment of rats with the first-in-class NAMPT stimulator, P7C3-A20, prevented behavioral and histologic indicators of peripheral neuropathy, stimulated tissue NAD recovery, improved general health, and abolished attrition produced by a near maximum-tolerated dose of PTX...
November 10, 2017: ELife
https://www.readbyqxmd.com/read/29122948/microrna-regulation-of-type-2-innate-lymphoid-cell-homeostasis-and-function-in-allergic-inflammation
#20
Priti B Singh, Heather H Pua, Hannah C Happ, Christoph Schneider, Jakob von Moltke, Richard M Locksley, Dirk Baumjohann, K Mark Ansel
MicroRNAs (miRNAs) exert powerful effects on immunity through coordinate regulation of multiple target genes in a wide variety of cells. Type 2 innate lymphoid cells (ILC2s) are tissue sentinel mediators of allergic inflammation. We established the physiological requirements for miRNAs in ILC2 homeostasis and immune function and compared the global miRNA repertoire of resting and activated ILC2s and T helper type 2 (TH2) cells. After exposure to the natural allergen papain, mice selectively lacking the miR-17∼92 cluster in ILC2s displayed reduced lung inflammation...
November 9, 2017: Journal of Experimental Medicine
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