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https://www.readbyqxmd.com/read/29773710/arginine-methylation-is-required-for-canonical-wnt-signaling-and-endolysosomal-trafficking
#1
Lauren V Albrecht, Diego Ploper, Nydia Tejeda-Muñoz, Edward M De Robertis
Arginine methylation has emerged as a widespread and reversible protein modification with the potential to regulate a multitude of cellular processes, but its function is poorly understood. Endolysosomes play an important role in Wnt signaling, in which glycogen synthase kinase 3 (GSK3) becomes sequestered inside multivesicular bodies (MVBs) by the process known as microautophagy, causing the stabilization of many proteins. Up to 20% of cellular proteins contain three or more consecutive putative GSK3 sites, and of these 33% also contain methylarginine (meArg) modifications...
May 17, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29727702/prmt1-regulates-craniofacial-bone-formation-upstream-of-msx1
#2
Yongchao Gou, Jingyuan Li, Jian Wu, Rahul Gupta, Ihnbae Cho, Thach-Vu Ho, Yang Chai, Amy Merrill, Jun Wang, Jian Xu
Protein arginine methylation has been recently identified as an important form of post-translational modification (PTM). It is carried out by the protein arginine methyltransferase (PRMT) family of enzymes, which in mammals consists of nine members. Among them, PRMT1 is the major arginine methyltransferase and participates in transcription, signal transduction, development and cancer. The function of PRMT1 in craniofacial development remains unclear. We generated Wnt1-Cre;Prmt1fl/fl mice with cranial neural crest (CNC)-specific deletion of Prmt1 and compared CNC-derived craniofacial bones from newborn control and Wnt1-Cre;Prmt1fl/fl mice...
May 1, 2018: Mechanisms of Development
https://www.readbyqxmd.com/read/29695495/multiple-arginine-residues-are-methylated-in-drosophila-mre11-and-required-for-survival-following-ionizing-radiation
#3
Qing Yuan, Ran Tian, Haiying Zhao, Lijuan Li, Xiaolin Bi
Mre11 is a key player for DNA double strand break repair. Previous studies have shown that mammalian Mre11 is methylated at multiple arginines in its C-terminal Glycine-Arginine-Rich motif (GAR) by protein arginine methyltransferase PRMT1. Here, we found that the Drosophila Mre11 is methylated at arginines 559, 563, 565, and 569 in the GAR motif by DART1, the Drosophila homolog of PRMT1. Mre11 interacts with DART1 in S2 cells, and this interaction does not require the GAR motif. Arginines methylated Mre11 localizes exclusively in the nucleus as soluble nuclear protein or chromatin-binding protein...
April 25, 2018: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/29683372/modulating-the-expression-of-chtop-a-versatile-regulator-of-gene-specific-transcription-and-mrna-export
#4
Keiichi Izumikawa, Hideaki Ishikawa, Richard J Simpson, Nobuhiro Takahashi
Chtop binds competitively to the arginine methyltransferases PRMT1 and PRMT5, thereby promoting the asymmetric or symmetric methylation of arginine residues, respectively. In cooperation with PRMT1, Chtop activates transcription of certain gene groups, such as the estrogen-inducible genes in breast cancer cells, the 5-hydroxymethylcytosine-modified genes involved in glioblastomagenesis, or the Zbp-89-dependent genes in erythroleukemia cells. Chtop also represses expression of the fetal γ-globin gene. In addition, Chtop is a component of the TREX complex that links transcription elongation to mRNA export...
April 23, 2018: RNA Biology
https://www.readbyqxmd.com/read/29665354/prmt1-negatively-regulates-activation-induced-cell-death-in-macrophages-by-arginine-methylation-of-gapdh
#5
Jun-Ho Cho, Rana Lee, Eunju Kim, Yea Eun Choi, Eui-Ju Choi
Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is implicated in cell death in addition to a role as a glycolytic enzyme. In particular, when cells are exposed to cellular stressors involving nitric oxide (NO) production, GAPDH can undergo NO-induced S-nitrosylation and S-nitrosylated GAPDH has been shown to elicit apoptosis. However, the mechanism underlying the regulation of the pro-apoptotic function of GAPDH remains unclear. Here, we found that protein arginine methyltransferase 1 (PRMT1) mediated arginine methylation of GAPDH in primary bone marrow-derived macrophages in a NO-dependent manner...
April 14, 2018: Experimental Cell Research
https://www.readbyqxmd.com/read/29651020/gfi1-facilitates-efficient-dna-repair-by-regulating-prmt1-dependent-methylation-of-mre11-and-53bp1
#6
Charles Vadnais, Riyan Chen, Jennifer Fraszczak, Zhenbao Yu, Jonathan Boulais, Jordan Pinder, Daria Frank, Cyrus Khandanpour, Josée Hébert, Graham Dellaire, Jean-François Côté, Stéphane Richard, Alexandre Orthwein, Elliot Drobetsky, Tarik Möröy
GFI1 is a transcriptional regulator expressed in lymphoid cells, and an "oncorequisite" factor required for development and maintenance of T-lymphoid leukemia. GFI1 deletion causes hypersensitivity to ionizing radiation, for which the molecular mechanism remains unknown. Here, we demonstrate that GFI1 is required in T cells for the regulation of key DNA damage signaling and repair proteins. Specifically, GFI1 interacts with the arginine methyltransferase PRMT1 and its substrates MRE11 and 53BP1. We demonstrate that GFI1 enables PRMT1 to bind and methylate MRE11 and 53BP1, which is necessary for their function in the DNA damage response...
April 12, 2018: Nature Communications
https://www.readbyqxmd.com/read/29628326/identification-of-a-novel-selective-small-molecule-inhibitor-of-protein-arginine-methyltransferase-5-prmt5-by-virtual-screening-resynthesis-and-biological-evaluations
#7
Kongkai Zhu, Chengshi Jiang, Hongrui Tao, Jingqiu Liu, Hua Zhang, Cheng Luo
As one of the most promising anticancer target in protein arginine methyltransferase (PRMT) family, PRMT5 has been drawing more and more attentions, and many efforts have been devoted to develop its inhibitors. In this study, three PRMT5 inhibitors (9, 16, and 23) with novel scaffolds were identified by performing pharmacophore- and docking-based virtual screening combined with in vitro radiometric-based scintillation proximity assay (SPA). Substructure search based on the scaffold of the most active 9 afforded 26 additional analogues, and SPA results indicated that two analogues (9-1 and 9-2) showed increased PRMT5 inhibitory activity compared with the parental compound...
March 30, 2018: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29540535/target-identification-reveals-protein-arginine-methyltransferase-1-is-a-potential-target-of-phenyl-vinyl-sulfone-and-its-derivatives
#8
Cheng-Han Yu, Chi-Chi Chou, Der-Yen Lee, Kay-Hooi Khoo, Geen-Dong Chang
Phenyl vinyl sulfone (PVS) and phenyl vinyl sulfonate (PVSN) inactivate protein tyrosine phosphatases (PTPs) by mimicking the phosphotyrosine structure and providing a Michael addition acceptor for the active-site cysteine residue of PTPs, thus forming covalent adducts between PVS (or PVSN) and PTPs. We developed a specific antiserum against PVS. This antiserum can be used in general antibody-based assays such as immunoblotting, immunofluorescence staining, and immunoprecipitation. Target identification through immunoprecipitation and mass spectrometry analysis reveals potential targets of PVS, mostly proteins with reactive cysteine residues or low-pKa cysteine residues that are prone to reversible redox modifications...
March 14, 2018: Bioscience Reports
https://www.readbyqxmd.com/read/29535867/detection-of-prmt1-inhibitors-with-stopped-flow-fluorescence
#9
Kun Qian, Hao Hu, Hui Xu, Y George Zheng
Protein arginine methyltransferases (PRMTs) are crucial epigenetic regulators in eukaryotic organisms that serve as histone writers for chromatin remodeling. PRMTs also methylate a variety of non-histone protein substrates to modulate their function and activity. The development of potent PRMT inhibitors has become an emerging and imperative research area in the drug discovery field to provide novel therapeutic agents for treating diseases and as tools to investigate the biological functions of PRMTs. PRMT1 is the major type I enzyme that catalyzes the formation of asymmetric dimethyl arginine, and PRMT1 plays important regulatory roles in signal transduction, transcriptional activation, RNA splicing, and DNA repair...
2018: Signal Transduction and Targeted Therapy
https://www.readbyqxmd.com/read/29456659/prmt1-rbm15-axis-regulates-megakaryocytic-differentiation-of-human-umbilical-cord-blood-cd34-cells
#10
Shuiling Jin, Yanfang Mi, Jing Song, Peipei Zhang, Yanyan Liu
Protein arginine methyltransferase 1 (PRMT1) serves pivotal roles in various cellular processes. However, its role in megakaryocytic differentiation has not been clearly reported. The aim of the present study was to explore the role of the PRMT-RNA binding motif protein 15 (RBM15) axis in human MK differentiation and the feasibility of targeting PRMT1 for leukemia treatment. In the present study, PRMT1 was overexpressed and the RBM15 protein was knocked down in human umbilical cord blood cluster of differentiation (CD)34+ cells and the cells were then cultured in megakaryocytic differentiation medium...
March 2018: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29429994/flip-the-switch-btg2-prmt1-protein-complexes-antagonize-pre-b-cell-proliferation-to-promote-b-cell-development
#11
Glendon S Wu, Craig H Bassing
No abstract text is available yet for this article.
February 12, 2018: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/29420098/smad6-methylation-represses-nf%C3%AE%C2%BAb-activation-and-periodontal-inflammation
#12
T Zhang, J Wu, N Ungvijanpunya, O Jackson-Weaver, Y Gou, J Feng, T V Ho, Y Shen, J Liu, S Richard, J Jin, G Hajishengallis, Y Chai, J Xu
The balance between pro- and anti-inflammatory signals maintains tissue homeostasis and defines the outcome of chronic inflammatory diseases such as periodontitis, a condition that afflicts the tooth-supporting tissues and exerts an impact on systemic health. The induction of tissue inflammation relies heavily on Toll-like receptor (TLR) signaling, which drives a proinflammatory pathway through recruiting myeloid differentiation primary response gene 88 (MyD88) and activating nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB)...
February 1, 2018: Journal of Dental Research
https://www.readbyqxmd.com/read/29383172/novel-prognostic-marker-prmt1-regulates-cell-growth-via-downregulation-of-cdkn1a-in-hcc
#13
Jea-Woon Ryu, Seon-Kyu Kim, Mi-Young Son, Su-Jin Jeon, Jung-Hwa Oh, Jung Hwa Lim, Sunwha Cho, Cho-Rok Jung, Ryuji Hamamoto, Dae-Soo Kim, Hyun-Soo Cho
Hepatocellular carcinoma (HCC) is a major type of liver cancer caused by the hepatitis B and C viruses, alcohol and exposure to aflatoxin. For HCC treatment, anticancer drugs have been widely used, but drug resistance in advanced HCC is an important problem, resulting in a continuous need for novel therapeutic targets. Therefore, in this study, we established a screening pipeline based on RNA-seq to screen novel therapeutic/prognostic targets in HCC and identified PRMT1 (Protein Arginine Methyltransferase 1)...
December 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29361115/the-gata-transcription-factor-elt-2-modulates-both-the-expression-and-methyltransferase-activity-of-prmt-1-in-caenorhabditis-elegans
#14
Sho Araoi, Hiroaki Daitoku, Atsuko Yokoyama, Koichiro Kako, Keiko Hirota, Akiyoshi Fukamizu
Protein arginine methyltransferase 1 (PRMT1) catalyzes asymmetric arginine dimethylation of cellular proteins and thus modulates various biological processes, including gene regulation, RNA metabolism, cell signaling and DNA repair. Since prmt-1 null mutant completely abolishes asymmetric dimethylarginine in C. elegans, PRMT-1 is thought to play a crucial role in determining levels of asymmetric arginine dimethylation. However, the mechanism underlying the regulation of PRMT-1 activity remains largely unknown...
May 1, 2018: Journal of Biochemistry
https://www.readbyqxmd.com/read/29326975/identifying-the-substrate-proteins-of-u-box-e3s-e4b-and-chip-by-orthogonal-ubiquitin-transfer
#15
Karan Bhuripanyo, Yiyang Wang, Xianpeng Liu, Li Zhou, Ruochuan Liu, Duc Duong, Bo Zhao, Yingtao Bi, Han Zhou, Geng Chen, Nicholas T Seyfried, Walter J Chazin, Hiroaki Kiyokawa, Jun Yin
E3 ubiquitin (UB) ligases E4B and carboxyl terminus of Hsc70-interacting protein (CHIP) use a common U-box motif to transfer UB from E1 and E2 enzymes to their substrate proteins and regulate diverse cellular processes. To profile their ubiquitination targets in the cell, we used phage display to engineer E2-E4B and E2-CHIP pairs that were free of cross-reactivity with the native UB transfer cascades. We then used the engineered E2-E3 pairs to construct "orthogonal UB transfer (OUT)" cascades so that a mutant UB (xUB) could be exclusively used by the engineered E4B or CHIP to label their substrate proteins...
January 2018: Science Advances
https://www.readbyqxmd.com/read/29208765/protein-arginine-methyltransferase-expression-and-activity-during-myogenesis
#16
Nicole Y Shen, Sean Y Ng, Stephen L Toepp, Vladimir Ljubicic
Despite the emerging importance of protein arginine methyltransferases (PRMTs) in regulating skeletal muscle plasticity, PRMT biology during muscle development is complex and not completely understood. Therefore, our purpose was to investigate PRMT1, -4, and -5 expression and function in skeletal muscle cells during the phenotypic remodeling elicited by myogenesis. C2 C12 muscle cell maturation, assessed during the myoblast (MB) stage, and during days 1, 3, 5, and 7 of differentiation, was employed as an in vitro model of myogenesis...
February 28, 2018: Bioscience Reports
https://www.readbyqxmd.com/read/29193371/differential-interaction-of-prmt1-with-rgg-boxes-of-the-fet-family-proteins-ews-and-taf15
#17
Kim K C Li, Bess L Chau, Kevin A W Lee
The FET sub-family (FUS/TLS, EWS, TAF15) of RNA-binding proteins have remarkably similar overall structure but diverse biological and pathological roles. The molecular basis for FET protein specialization is largely unknown. Gly-Arg-Rich regions (RGG-boxes) within FET proteins are targets for methylation by Protein-Arginine-Methyl-Transferase-1 (PRMT1) and substrate capture is thought to involve electrostatic attraction between positively charged polyRGG substrates and negatively charged surface channels of PRMT1...
March 2018: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/29186683/trim48-promotes-ask1-activation-and-cell-death-through-ubiquitination-dependent-degradation-of-the-ask1-negative-regulator-prmt1
#18
Yusuke Hirata, Kazumi Katagiri, Keita Nagaoka, Tohru Morishita, Yuki Kudoh, Tomohisa Hatta, Isao Naguro, Kuniyuki Kano, Tsuyoshi Udagawa, Tohru Natsume, Junken Aoki, Toshifumi Inada, Takuya Noguchi, Hidenori Ichijo, Atsushi Matsuzawa
Apoptosis signal-regulating kinase 1 (ASK1) is an oxidative stress-responsive kinase that is regulated by various interacting molecules and post-translational modifications. However, how these molecules and modifications cooperatively regulate ASK1 activity remains largely unknown. Here, we showed that tripartite motif 48 (TRIM48) orchestrates the regulation of oxidative stress-induced ASK1 activation. A pull-down screen identified a TRIM48-interacting partner, protein arginine methyltransferase 1 (PRMT1), which negatively regulates ASK1 activation by enhancing its interaction with thioredoxin (Trx), another ASK1-negative regulator...
November 28, 2017: Cell Reports
https://www.readbyqxmd.com/read/29183786/characterization-of-protein-methyltransferases-rkm1-rkm4-efm4-efm7-set5-and-hmt1-reveals-extensive-post-translational-modification
#19
Daniel L Winter, Gene Hart-Smith, Marc R Wilkins
Protein methylation is one of the major post-translational modifications (PTMs) in the cell. In Saccharomyces cerevisiae, over 20 protein methyltransferases (MTases) and their respective substrates have been identified. However, the way in which these MTases are modified and potentially subject to regulation remains poorly understood. Here, we investigated six overexpressed S. cerevisiae protein MTases (Rkm1, Rkm4, Efm4, Efm7, Set5 and Hmt1) to identify PTMs of potential functional relevance. We identified 48 PTM sites across the six MTases, including phosphorylation, acetylation and methylation...
January 5, 2018: Journal of Molecular Biology
https://www.readbyqxmd.com/read/29129692/prmt1-mediates-podocyte-injury-and-glomerular-fibrosis-through-phosphorylation-of-erk-pathway
#20
Yu Zhu
Diabetic nephropathy (DN) is characterized by a change of glomerular structure and dysfunction of filtration barrier, which significantly accompanied by podocytes apoptosis and glomerular fibrosis. Angiotensin Ⅱ(Ang Ⅱ) induced activation of ERK1/2 signaling plays important roles in causing apoptosis of podocytes in DN kidneys. Previous studies have shown that PRMT1 have a pro-inflammatory function through activating ERK1/2 signaling pathway during development of chronic pulmonary disease, however, its role in DN development has not been investigated...
January 1, 2018: Biochemical and Biophysical Research Communications
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