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https://www.readbyqxmd.com/read/28695742/the-human-regulatory-protein-ki-1-57-is-a-target-of-sumoylation-and-affects-pml-nuclear-body-formation
#1
Ângela Saito, Edmarcia E de Souza, Fernanda C Costa, Gabriela V Meirelles, Kaliandra de Almeida Gonçalves, Marcos T Santos, Gustavo C Bressan, Mark E McComb, Catherine E Costello, Stephen A Whelan, Jörg Kobarg
Ki-1/57 is a nuclear and cytoplasmic regulatory protein first identified in malignant cells from Hodgkin's lymphoma. It is involved in gene expression regulation on both transcriptional and mRNA metabolism levels. Ki-1/57 belongs to the family of intrinsically unstructured proteins, undergoes phosphorylation by PKC and methylation by PRMT1. Previous characterization of its protein interaction profile by yeast two-hybrid screening showed that Ki- 1/57 interacts with proteins of the SUMOylation machinery: the SUMO E2 conjugating enzyme UBC9 and the SUMO E3 ligase PIAS3, which suggested that Ki-1/57 could be involved with this process...
July 11, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28695568/prmt1-regulates-astrocytic-differentiation-of-embryonic-neural-stem-precursor-cells
#2
Mizuki Honda, Kinichi Nakashima, Sayako Katada
Arginine methylation is a posttranslational modification which is catalyzed by protein arginine methyltransferases (PRMTs). Here, we report that PRMT1 is highly expressed in neural stem/precursor cells (NS/PCs) of mouse embryos, and knockdown of PRMT1 in NS/PCs suppresses the generation of astrocytes. The luciferase assay demonstrated that knockdown of PRMT1 inhibits activation of the promoter of a typical astrocytic marker gene, glial fibrillary acidic protein (Gfap), in NS/PCs. The transcription factor signal transducer and activator of transcription 3 (STAT3) is known to generally be critical for astrocytic differentiation of NS/PCs...
July 11, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28671608/lipotoxicity-induced-prmt1-exacerbates-mesangial-cell-apoptosis-via-endoplasmic-reticulum-stress
#3
Min-Jung Park, Ho Jae Han, Dong-Il Kim
Lipotoxicity-induced mesangial cell apoptosis is implicated in the exacerbation of diabetic nephropathy (DN). Protein arginine methyltransferases (PRMTs) have been known to regulate a variety of biological functions. Recently, it was reported that PRMT1 expression is increased in proximal tubule cells under diabetic conditions. However, their roles in mesangial cells remain unexplored. Thus, we examined the pathophysiological roles of PRMTs in mesangial cell apoptosis. Treatment with palmitate, which mimics cellular lipotoxicity, induced mesangial cell apoptosis via protein kinase RNA-like endoplasmic reticulum kinase (PERK) and ATF6-mediated endoplasmic reticulum (ER) stress signaling...
July 3, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28656289/prmt1-expression-is-elevated-in-head-and-neck-cancer-and-inhibition-of-protein-arginine-methylation-by-adenosine-dialdehyde-or-prmt1-knockdown-downregulates-proliferation-and-migration-of-oral-cancer-cells
#4
Chun-Yi Chuang, Chien-Ping Chang, Yu-Jen Lee, Wei-Long Lin, Wen-Wei Chang, Jia-Sian Wu, Ya-Wen Cheng, Huei Lee, Chuan Li
Protein arginine methylation is a post-translational modification that has been implicated in signal transduction, gene transcription, DNA repair and RNA processing. Overexpression or deregulation of protein arginine methyltransferases (PRMTs) have been reported to be associated with various cancers but have not been studied in head and neck cancer (HNC). We investigated the involvement of the modification in HNC using oral cancer cell lines (SAS, OECM-1 and HSC-3) and an immortalized normal oral cells (S-G)...
June 21, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28655788/prmt1-mediated-translation-regulation-is-a-crucial-vulnerability-of-cancer
#5
Jessie Hao-Ru Hsu, Benjamin Hubbell-Engler, Guillaume Adelmant, Jialiang Huang, Cailin E Joyce, Francisca Vazquez, Barbara A Weir, Philip Montgomery, Aviad Tsherniak, Andrew O Giacomelli, Jennifer A Perry, Jennifer Trowbridge, Yuko Fujiwara, Glenn S Cowley, Huafeng Xie, Woojin Kim, Carl D Novina, William C Hahn, Jarrod A Marto, Stuart H Orkin
Through an shRNA screen we identified the protein arginine methyltransferase Prmt1 as a vulnerable intervention point in murine p53/Rb-null osteosarcomas, the human counterpart of which lacks effective therapeutic options. Depletion of Prmt1 in p53-deficient cells impaired tumor initiation and maintenance in vitro and in vivo Mechanistic studies reveal that translation-associated pathways were enriched for Prmt1 downstream targets, implicating Prmt1 in translation control. In particular, loss of Prmt1 led to a decrease in arginine methylation of the translation initiation complex, thereby disrupting its assembly and inhibiting translation...
June 27, 2017: Cancer Research
https://www.readbyqxmd.com/read/28652407/arginine-methylation-regulates-c-myc-dependent-transcription-by-altering-promoter-recruitment-of-the-acetyltransferase-p300
#6
Irina Tikhanovich, Jie Zhao, Brian Bridges, Sean Kumer, Ben Roberts, Steven A Weinman
Protein arginine methyltransferase 1 (PRMT1) is an essential gene controlling about 85% of total cellular arginine methylation in proteins. We have previously shown that PRMT1 is an important regulator of innate immune responses and that it is required for M2 macrophage differentiation. c-Myc is a transcription factor that is critical in regulating cell proliferation and also regulates the M2 transcriptional program in macrophages. Here, we sought to determine whether c-Myc in myeloid cells is regulated by PRMT1-dependent arginine methylation...
June 26, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28649316/discovery-of-decamidine-as-a-new-and-potent-prmt1-inhibitor
#7
Jing Zhang, Kun Qian, Chunli Yan, Maomao He, Brenson A Jassim, Ivaylo Ivanov, Yujun George Zheng
Protein arginine methyltransferase 1 (PRMT1) is a key player for the dynamic regulation of arginine methylation. Its dysregulation and aberrant expression are implicated in various pathological conditions, and a plethora of evidence suggests that PRMT1 inhibition is of significant therapeutic value. Herein, we reported the modification of a series of diamidine compounds with varied lengths in the middle alkyl linker for PRMT1 inhibition. Decamidine (2j), which possesses the longest linker in the series, displayed 2- and 4- fold increase in PRMT1 inhibition (IC50 = 13 μM), as compared with furamdine and stilbamidine...
February 1, 2017: MedChemComm
https://www.readbyqxmd.com/read/28644004/intricate-effects-of-%C3%AE-amino-and-lysine-modifications-on-arginine-methylation-of-the-n-terminal-tail-of-histone-h4
#8
Melody D Fulton, Jing Zhang, Maomao He, Meng-Chiao Ho, Y George Zheng
Chemical modifications of the DNA and nucleosomal histones tightly control the gene transcription program in eukaryotic cells. The "histone code" hypothesis proposes that the frequency, combination, and location of post-translational modifications (PTMs) of the core histones compose a complex network of epigenetic regulation. Currently, there are at least 23 different types and >450 histone PTMs that have been discovered, and the PTMs of lysine and arginine residues account for a crucial part of the histone code...
July 7, 2017: Biochemistry
https://www.readbyqxmd.com/read/28643125/the-role-of-prmt1-in-egfr-methylation-and-signaling-in-mda-mb-468-triple-negative-breast-cancer-cells
#9
Katsuya Nakai, Weiya Xia, Hsin-Wei Liao, Mitsue Saito, Mien-Chie Hung, Hirohito Yamaguchi
BACKGROUND: Epidermal growth factor receptor (EGFR) is often overexpressed in triple-negative breast cancer (TNBC). However, clinical studies have shown that therapies against EGFR are not effective in patients with TNBC. Recently, it has been reported that arginine 198/200 in EGFR extracellular domain is methylated by PRMT1 and that the methylation confers resistance to EGFR monoclonal antibody cetuximab in colorectal cancer cells. To explore a potential mechanism underlying intrinsic resistance to anti-EGFR therapy in TNBC, we investigated the role of PRMT1 in EGFR methylation and signaling in MDA-MB-468 (468) TNBC cells...
June 22, 2017: Breast Cancer: the Journal of the Japanese Breast Cancer Society
https://www.readbyqxmd.com/read/28636189/discovery-of-alkyl-bis-oxy-dibenzimidamide-derivatives-as-novel-protein-arginine-methyltransferase-1-prmt1-inhibitors
#10
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
#11
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...
August 2017: Nature Immunology
https://www.readbyqxmd.com/read/28591869/alternative-splicing-of-cnot7-diversifies-ccr4-not-functions
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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