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https://www.readbyqxmd.com/read/28636189/discovery-of-alkyl-bis-oxy-dibenzimidamide-derivatives-as-novel-protein-arginine-methyltransferase-1-prmt1-inhibitors
#1
Wei-Yao Zhang, Wen-Chao Lu, Hao Jiang, Zheng-Bing Lv, Yi-Qian Xie, Fu-Lin Lian, Zhong-Jie Liang, Yu-Xi Jiang, Da-Jin Wang, Cheng Luo, Jia Jin, Fei Ye
Protein arginine methylation, a post-translational modification critical for a variety of biological processes, is catalyzed by protein arginine N-methyltransferases (PRMTs). In particular, PRMT1 is responsible for over 85% of the arginine methylation in mammalian cells. Dysregulation of PRMT1 is involved in diverse pathological diseases including cancers. However, most current PRMT1inhibitors are lack of specificity, efficacy, and bioavailability. Herein, a series of alkyl bis(oxy)dibenzimidamide derivatives were identified as selective PRMT1 inhibitors...
June 21, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/28628091/the-btg2-prmt1-module-limits-pre-b-cell-expansion-by-regulating-the-cdk4-cyclin-d3-complex
#2
Elmar Dolezal, Simona Infantino, Friedel Drepper, Theresa Börsig, Aparajita Singh, Thomas Wossning, Gina J Fiala, Susana Minguet, Bettina Warscheid, David M Tarlinton, Hassan Jumaa, David Medgyesi, Michael Reth
Developing pre-B cells in the bone marrow alternate between proliferation and differentiation phases. We found that protein arginine methyl transferase 1 (PRMT1) and B cell translocation gene 2 (BTG2) are critical components of the pre-B cell differentiation program. The BTG2-PRMT1 module induced a cell-cycle arrest of pre-B cells that was accompanied by re-expression of Rag1 and Rag2 and the onset of immunoglobulin light chain gene rearrangements. We found that PRMT1 methylated cyclin-dependent kinase 4 (CDK4), thereby preventing the formation of a CDK4-Cyclin-D3 complex and cell cycle progression...
June 19, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28591869/alternative-splicing-of-cnot7-diversifies-ccr4-not-functions
#3
Clément Chapat, Kamel Chettab, Pierre Simonet, Peng Wang, Pierre De La Grange, Muriel Le Romancer, Laura Corbo
The CCR4-associated factor CAF1, also called CNOT7, is a catalytic subunit of the CCR4-NOT complex, which has been implicated in all aspects of the mRNA life cycle, from mRNA synthesis in the nucleus to degradation in the cytoplasm. In human cells, alternative splicing of the CNOT7 gene yields a second CNOT7 transcript leading to the formation of a shorter protein, CNOT7 variant 2 (CNOT7v2). Biochemical characterization indicates that CNOT7v2 interacts with CCR4-NOT subunits, although it does not bind to BTG proteins...
June 7, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28545085/splicing-factor-sf3b1k700e-mutant-dysregulates-erythroid-differentiation-via-aberrant-alternative-splicing-of-transcription-factor-tal1
#4
Shuiling Jin, Hairui Su, Ngoc-Tung Tran, Jing Song, Sydney S Lu, Ying Li, Suming Huang, Omar Abdel-Wahab, Yanyan Liu, Xinyang Zhao
More than 60% of myeloid dysplasia syndrome (MDS) contains mutations in genes encoding for splicing factors such as SF3B1, U2AF, SRSF2 and ZRSR2. Mutations in SF3B1 are associated with 80% cases of refractory anemia with ring sideroblast (RARS), a subtype of MDS. SF3B1K700E is the most frequently mutated site among mutations on SF3B1. Yet the molecular mechanisms on how mutations of splicing factors lead to defective erythropoiesis are not clear. SF3B1K700E mutant binds to an RNA binding protein, RBM15, stronger than the wild type SF3B1 protein in co-immunoprecipitation assays...
2017: PloS One
https://www.readbyqxmd.com/read/28524020/altered-gene-expression-of-epigenetic-modifying-enzymes-in-response-to-dietary-supplementation-with-linseed-oil
#5
Ran Li, Eveline M Ibeagha-Awemu
Recently we showed that 5% linseed oil (LSO) and 5% safflower oil (SFO) supplementation of cow's diets reduced milk fat yield by 30·38 and 32·42% respectively, accompanied by differential expression of genes and regulation by microRNAs (miRNA). This research communication addresses the hypothesis that epigenetic regulation could be involved in the observed milk fat reduction. Thus, this study investigated the gene expression pattern of major epigenetic modifying enzymes in response to dietary supplementation with LSO or SFO...
May 2017: Journal of Dairy Research
https://www.readbyqxmd.com/read/28506031/identification-and-characterization-of-protein-arginine-methyltransferase-1-in-acanthamoeba-castellanii
#6
Eun-Kyung Moon, Hyun-Hee Kong, Yeonchul Hong, Hae-Ahm Lee, Fu-Shi Quan
Protein arginine methyltransferase (PRMT) is an important epigenetic regulator in eukaryotic cells. During encystation, an essential process for Acanthamoeba survival, the expression of a lot of genes involved in the encystation process has to be regulated in order to be induced or inhibited. However, the regulation mechanism of these genes is yet unknown. In this study, the full-length 1,059 bp cDNA sequence of Acanthamoeba castellanii PRMT1 (AcPRMT1) was cloned for the first time. The AcPRMT1 protein comprised of 352 amino acids with a SAM-dependent methyltransferase PRMT-type domain...
April 2017: Korean Journal of Parasitology
https://www.readbyqxmd.com/read/28397890/discovery-and-optimization-of-selective-inhibitors-of-protein-arginine-methyltransferase-5-by-docking-based-virtual-screening
#7
Yan Ye, Bidong Zhang, Ruifeng Mao, Chenhua Zhang, Yulan Wang, Jing Xing, Yu-Chih Liu, Xiaomin Luo, Hong Ding, Yaxi Yang, Bing Zhou, Hualiang Jiang, Kaixian Chen, Cheng Luo, Mingyue Zheng
Protein arginine methyltransferase 5 (PRMT5) is a type II PRMT enzyme critical for diverse cellular processes and different types of cancers. Many efforts have been made to discover novel scaffold PRMT5 inhibitors. Herein, we report the discovery of DC_P33 as a hit compound of PRMT5 inhibitor, identified by molecular docking based virtual screening and (3)H-labeled radioactive methylation assays. Structure-activity relationship (SAR) analysis was performed on the analogs of DC_P33 and then structural modifications were done to improve its activity...
May 3, 2017: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/28392446/the-asymmetric-dimethylarginine-mediated-inhibition-of-nitric-oxide-in-the-rostral-ventrolateral-medulla-contributes-to-regulation-of-blood-pressure-in-hypertensive-rats
#8
Xing Tan, Ji-Kui Li, Jia-Cen Sun, Pei-Lei Jiao, Yang-Kai Wang, Zhao-Tang Wu, Bing Liu, Wei-Zhong Wang
Nitric oxide (NO) contributes to the central control of cardiovascular activity. The rostral ventrolateral medulla (RVLM) has been recognized as a pivotal region for maintaining basal blood pressure (BP) and sympathetic tone. It is reported that asymmetric dimethylarginine (ADMA), characterized as a cardiovascular risk marker, is an endogenous inhibitor of nitric oxide synthesis. The present was designed to determine the role of ADMA in the RVLM in the central control of BP in hypertensive rats. In Sprague Dawley (SD) rats, microinjection of ADMA into the RVLM dose-dependently increased BP, heart rate (HR), and renal sympathetic never activity (RSNA), but also reduced total NO production in the RVLM...
April 7, 2017: Nitric Oxide: Biology and Chemistry
https://www.readbyqxmd.com/read/28370799/through-modulation-of-cardiac-ca-2-handling-ucp2-affects-cardiac-electrophysiology-and-influences-the-susceptibility-for-ca-2-mediated-arrhythmias
#9
Robert Larbig, Sara Reda, Vera Paar, Andrea Trost, Johannes Leitner, Stephanie Weichselbaumer, Karolina A Motloch, Bernhard Wernly, Andreas Arrer, Benjamin Strauss, Michael Lichtenauer, Herbert A Reitsamer, Lars Eckardt, Guiscard Seebohm, Uta C Hoppe, Lukas J Motloch
Introduction UCP2 belongs to a superfamily of mitochondrial ion transporters. Due to its beneficial influence on production of reactive oxygen species it is suggested to reduce cardiac ischemic reperfusion injury. Recent studies uncovered its ability to regulate mitochondrial Ca(2+) -uptake and therefore to influence cardiac cytosolic Ca(2+) -handling, indicating compensatory pathways to avoid toxic Ca(2+) -overload in UCP2 knock-out mice (UCP2(-/-) ). However, the specific mechanisms and their impact on cardiac electrophysiology remain speculative...
March 31, 2017: Experimental Physiology
https://www.readbyqxmd.com/read/28330868/protein-arginine-methyltransferase-1-modulates-innate-immune-responses-through-regulation-of-peroxisome-proliferator-activated-receptor-%C3%AE-dependent-macrophage-differentiation
#10
Irina Tikhanovich, Jie Zhao, Jody Olson, Abby Adams, Ryan Taylor, Brian Bridges, Laurie Marshall, Benjamin Roberts, Steven A Weinman
Arginine methylation is a common posttranslational modification that has been shown to regulate both gene expression and extranuclear signaling events. We recently reported defects in protein arginine methyltransferase 1 (PRMT1) activity and arginine methylation in the livers of cirrhosis patients with a history of recurrent infections. To examine the role of PRMT1 in innate immune responses in vivo, we created a cell type-specific knock-out mouse model. We showed that myeloid-specific PRMT1 knock-out mice demonstrate higher proinflammatory cytokine production and a lower survival rate after cecal ligation and puncture...
April 28, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28326484/genome-wide-transcriptional-analysis-of-cardiovascular-related-genes-and-pathways-induced-by-pm2-5-in-human-myocardial-cells
#11
Lin Feng, Xiaozhe Yang, Collins Otieno Asweto, Jing Wu, Yannan Zhang, Hejing Hu, Yanfeng Shi, Junchao Duan, Zhiwei Sun
Air pollution has been a major environment-related health threat. Most of the studies on PM2.5 toxicity have verified on the cardiovascular system and endothelial cells. However, researches on PM2.5-induced myocardial-related toxicity are limited. This study aims to fully understand the toxic effects of PM2.5 on human myocardial cell (AC16) and explore its molecular mechanism based on microarray analysis and bioinformatics analysis. Microarray data analysis manifested that PM2.5-induced toxicity affected expression of 472 genes compared with the control group, including 166 upregulated genes and 306 downregulated genes in human myocardial (AC16) cells...
April 2017: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/28301308/regenerating-muscle-with-arginine-methylation
#12
Roméo S Blanc, Stéphane Richard
Protein arginine methyltransferase (PRMT) is a family of nine proteins catalyzing the methylation of arginine residues. They were recently shown to be essential for proper regeneration of skeletal muscles. However, the mechanisms triggering the methylation event, as well as how the methylated substrates regulate muscle stem cell function and fate decision remain to be determined. This point-of-view will discuss the recent findings on the specific role of PRMT1, CARM1/PRMT4, PRMT5, and PRMT7 in muscle stem cell fate guidance, and shed light on the future challenges which could help defining the therapeutic potential of PRMT inhibitors against muscular disorders and aging...
February 17, 2017: Transcription
https://www.readbyqxmd.com/read/28267599/the-rna-binding-protein-serbp1-interacts-selectively-with-the-signaling-protein-rack1
#13
Graeme B Bolger
The RACK1 protein interacts with numerous proteins involved in signal transduction, the cytoskeleton, and mRNA splicing and translation. We used the 2-hybrid system to identify additional proteins interacting with RACK1 and isolated the RNA-binding protein SERBP1. SERPB1 shares amino acid sequence homology with HABP4 (also known as Ki-1/57), a component of the RNA spicing machinery that has been shown previously to interact with RACK1. Several different isoforms of SERBP1, generated by alternative mRNA splicing, interacted with RACK1 with indistinguishable interaction strength, as determined by a 2-hybrid beta-galactosidase assay...
July 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28196873/lymphotoxin-beta-interacts-with-methylated-egfr-to-mediate-acquired-resistance-to-cetuximab-in-head-and-neck-cancer
#14
Dennis Shin-Shian Hsu, Wei-Lun Hwang, Chiou-Hwa Yuh, Chen-Hsi Chu, Yang-Hui Ho, Pon-Bo Chen, Han-Syuan Lin, Hua-Kuo Lin, Shih-Pei Wu, Chih-Yi Lin, Wen-Hao Hsu, Hsin-Yi Lan, Hsiao-Jung Wang, Shyh-Kuan Tai, Mien-Chie Hung, Muh-Hwa Yang
PURPOSE: In head and neck squamous cell carcinoma (HNSCC), the incidence of RAS mutation, which is the major cause of cetuximab resistance, is relatively rare compared with the other types of cancers, and the mechanism mediating acquired resistance is unclear compared with the driver gene mutation-mediated de novo resistance. Here we investigated the driver gene mutation-independent mechanism for cetuximab resistance in HNSCC. EXPERIMENTAL DESIGN: We used the in vitro-selected and in vivo-selected cetuximab-resistant sublines of HNSCC cell lines for investigating the mechanism of acquired resistance to cetuximab...
February 14, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28145161/repetitive-ischemia-increases-myocardial-dimethylarginine-dimethylaminohydrolase-1-expression
#15
Ping Zhang, John T Fassett, Guangshuo Zhu, Jingxin Li, Xinli Hu, Xin Xu, Yingjie Chen, Robert J Bache
Pharmacologic inhibition of nitric oxide production inhibits growth of coronary collateral vessels. Dimethylarginine dimethylaminohydrolase 1 (DDAH1) is the major enzyme that degrades asymmetric dimethylarginine (ADMA), a potent inhibitor of nitric oxide synthase. Here we examined regulation of the ADMA-DDAH1 pathway in a canine model of recurrent myocardial ischemia during the time when coronary collateral growth is known to occur. Under basal conditions, DDAH1 expression was non-uniform across the left ventricular (LV) wall, with expression strongest in the subepicardium...
January 1, 2017: Vascular Medicine
https://www.readbyqxmd.com/read/28143887/comparative-monomethylarginine-proteomics-suggests-that-protein-arginine-methyltransferase-1-prmt1-is-a-significant-contributor-to-arginine-monomethylation-in-toxoplasma-gondii
#16
Rama R Yakubu, Natalie C Silmon de Monerri, Edward Nieves, Kami Kim, Louis M Weiss
Arginine methylation is a common posttranslational modification found on nuclear and cytoplasmic proteins that has roles in transcriptional regulation, RNA metabolism and DNA repair. The protozoan parasite Toxoplasma gondii has a complex life cycle requiring transcriptional plasticity and has unique transcriptional regulatory pathways. Arginine methylation may play an important part in transcriptional regulation and splicing biology in this organism. The T. gondii genome contains five putative protein arginine methyltransferases (PRMTs), of which PRMT1 is important for cell division and growth...
April 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28126510/caveolin1-protein-arginine-methyltransferase1-sirtuin1-axis-as-a-potential-target-against-endothelial-dysfunction
#17
REVIEW
Soniya Charles, Vijay Raj, Jesu Arokiaraj, Kanchana Mala
Endothelial dysfunction (ED), an established response to cardiovascular risk factors, is characterized by increased levels of soluble molecules secreted by endothelial cells (EC). Evidence suggest that ED is an independent predictor of cardiac events and that it is associated with a deficiency in production or bioavailability of nitric oxide (NO) and/or an imbalance in the relative contribution of endothelium-derived relaxing and contracting factors. ED can be reversed by treating cardiovascular risk factors, hence, beyond ambiguity, ED contributes to initiation and progression of atherosclerotic disease...
May 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28094300/sequestration-of-prmt1-and-nd1-l-mrna-into-als-linked-fus-mutant-r521c-positive-aggregates-contributes-to-neurite-degeneration-upon-oxidative-stress
#18
Mi-Hee Jun, Hyun-Hee Ryu, Yong-Woo Jun, Tongtong Liu, Yan Li, Chae-Seok Lim, Yong-Seok Lee, Bong-Kiun Kaang, Deok-Jin Jang, Jin-A Lee
Mutations in fused in sarcoma (FUS), a DNA/RNA binding protein, are associated with familial amyotrophic lateral sclerosis (ALS). However, little is known about how ALS-causing mutations alter protein-protein and protein-RNA complexes and contribute to neurodegeneration. In this study, we identified protein arginine methyltransferase 1 (PRMT1) as a protein that more avidly associates with ALS-linked FUS-R521C than with FUS-WT (wild type) or FUS-P525L using co-immunoprecipitation and LC-MS analysis. Abnormal association between FUS-R521C and PRMT1 requires RNA, but not methyltransferase activity...
January 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28094290/protein-arginine-methyltransferase-1-prmt1-represses-mhc-ii-transcription-in-macrophages-by-methylating-ciita
#19
Zhiwen Fan, Jianfei Li, Ping Li, Qing Ye, Huihui Xu, Xiaoyan Wu, Yong Xu
Efficient presentation of alien antigens triggers activation of T lymphocytes and robust host defense against invading pathogens. This pathophysiological process relies on the expression of major histocompatibility complex (MHC) molecules in antigen presenting cells such as macrophages. Aberrant MHC II transactivation plays a crucial role in the pathogenesis of atherosclerosis. Class II transactivator (CIITA) mediates MHC II induction by interferon gamma (IFN-γ). CIITA activity can be fine-tuned at the post-translational level, but the mechanisms are not fully appreciated...
January 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28057797/prmt2-interacts-with-splicing-factors-and-regulates-the-alternative-splicing-of-bcl-x
#20
Mynol I Vhuiyan, Magnolia L Pak, Margaret A Park, Dylan Thomas, Ted M Lakowski, Charles E Chalfant, Adam Frankel
Protein arginine N-methyltransferase 2 (PRMT2) functions in JAK-STAT and Wnt/β-catenin signaling pathways, serves as a nuclear receptor-dependent transcriptional co-activator, and represses NF-κB and E2F1 transcription factor activities to promote apoptosis. We have previously demonstrated that PRMT2 interacts with PRMT1 and increases its activity. Here, we reveal associations using proteomics between the PRMT2 SH3 domain and splicing factors including Src-associated in mitosis 68 kDa protein (SAM68), a PRMT1 substrate and trans-acting factor that mediates BCL-X alternative splicing...
January 5, 2017: Journal of Biochemistry
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