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Arginine methylation t cell

Lindsay M Webb, Stephanie A Amici, Kyle A Jablonski, Himanshu Savardekar, Amanda R Panfil, Linsen Li, Wei Zhou, Kevin Peine, Vrajesh Karkhanis, Eric M Bachelder, Kristy M Ainslie, Patrick L Green, Chenglong Li, Robert A Baiocchi, Mireia Guerau-de-Arellano
In the autoimmune disease multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE), expansion of pathogenic, myelin-specific Th1 cell populations drives active disease; selectively targeting this process may be the basis for a new therapeutic approach. Previous studies have hinted at a role for protein arginine methylation in immune responses, including T cell-mediated autoimmunity and EAE. However, a conclusive role for the protein arginine methyltransferase (PRMT) enzymes that catalyze these reactions has been lacking...
January 13, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
Jennifer K Trittmann, Yi Jin, Louis G Chicoine, Yusen Liu, Bernadette Chen, Leif D Nelin
Arginase and nitric oxide synthase (NOS) share a common substrate, l-arginine, and have opposing effects on vascular remodeling. Arginase is the first step in polyamine and proline synthesis necessary for cellular proliferation, while NO produced from NOS promotes apoptosis. Previously, we identified a single nucleotide polymorphism (SNP) in the arginase-1 (ARG1) gene, rs2781666 (T-allele) that was associated with a decreased risk for developing pulmonary hypertension (PH) in a cohort of infants with bronchopulmonary dysplasia (BPD)...
November 2016: Physiological Reports
Corina T Madreiter-Sokolowski, Christiane Klec, Warisara Parichatikanond, Sarah Stryeck, Benjamin Gottschalk, Sergio Pulido, Rene Rost, Emrah Eroglu, Nicole A Hofmann, Alexander I Bondarenko, Tobias Madl, Markus Waldeck-Weiermair, Roland Malli, Wolfgang F Graier
Recent studies revealed that mitochondrial Ca(2+) channels, which control energy flow, cell signalling and death, are macromolecular complexes that basically consist of the pore-forming mitochondrial Ca(2+) uniporter (MCU) protein, the essential MCU regulator (EMRE), and the mitochondrial Ca(2+) uptake 1 (MICU1). MICU1 is a regulatory subunit that shields mitochondria from Ca(2+) overload. Before the identification of these core elements, the novel uncoupling proteins 2 and 3 (UCP2/3) have been shown to be fundamental for mitochondrial Ca(2+) uptake...
September 19, 2016: Nature Communications
Wei-Chih Tsai, Sitaram Gayatri, Lucas C Reineke, Gianluca Sbardella, Mark T Bedford, Richard E Lloyd
Stress granules (SGs) are cytoplasmic condensates of stalled messenger ribonucleoprotein complexes (mRNPs) that form when eukaryotic cells encounter environmental stress. RNA-binding proteins are enriched for arginine methylation and facilitate SG assembly through interactions involving regions of low amino acid complexity. How methylation of specific RNA-binding proteins regulates RNA granule assembly has not been characterized. Here, we examined the potent SG-nucleating protein Ras-GAP SH3-binding protein 1 (G3BP1), and found that G3BP1 is differentially methylated on specific arginine residues by protein arginine methyltransferase (PRMT) 1 and PRMT5 in its RGG domain...
October 21, 2016: Journal of Biological Chemistry
Allison Eberhardt, Jeanne N Hansen, Jan Koster, Louis T Lotta, Simeng Wang, Emmett Livingstone, Kun Qian, Linda J Valentijn, Yujun George Zheng, Nina F Schor, Xingguo Li
Amplification or overexpression of MYCN is associated with poor prognosis of human neuroblastoma. We have recently defined a MYCN-dependent transcriptional signature, including protein arginine methyltransferase 1 (PRMT1), which identifies a subgroup of patients with high-risk disease. Here we provide several lines of evidence demonstrating PRMT1 as a novel regulator of MYCN and implicating PRMT1 as a potential therapeutic target in neuroblastoma pathogenesis. First, we observed a strong correlation between MYCN and PRMT1 protein levels in primary neuroblastoma tumors...
September 27, 2016: Oncotarget
Fabio Marino, Geert P M Mommen, Anita Jeko, Hugo D Meiring, Jacqueline A M van Gaans-van den Brink, Richard A Scheltema, Cécile A C M van Els, Albert J R Heck
Alterations in protein post-translational modification (PTM) are recognized hallmarks of diseases. These modifications potentially provide a unique source of disease-related human leukocyte antigen (HLA) class I-presented peptides that can elicit specific immune responses. While phosphorylated HLA peptides have already received attention, arginine methylated HLA class I peptide presentation has not been characterized in detail. In a human B-cell line we detected 149 HLA class I peptides harboring mono- and/or dimethylated arginine residues by mass spectrometry...
January 6, 2017: Journal of Proteome Research
Y K Banasavadi-Siddegowda, L Russell, E Frair, V A Karkhanis, T Relation, J Y Yoo, J Zhang, S Sif, J Imitola, R Baiocchi, B Kaur
Glioblastoma (GBM) represents the most common and aggressive histologic subtype among malignant astrocytoma and is associated with poor outcomes because of heterogeneous tumour cell population including mature non-stem-like cell and immature stem-like cells within the tumour. Thus, it is critical to find new target-specific therapeutic modalities. Protein arginine methyltransferase enzyme 5 (PRMT5) regulates many cellular processes through its methylation activity and its overexpression in GBM is associated with more aggressive disease...
January 12, 2017: Oncogene
Ji Hye Kim, Byong Chul Yoo, Woo Seok Yang, Eunji Kim, Sungyoul Hong, Jae Youl Cho
Protein arginine methyltransferases (PRMTs) mediate the methylation of a number of protein substrates of arginine residues and serve critical functions in many cellular responses, including cancer development, progression, and aggressiveness, T-lymphocyte activation, and hepatic gluconeogenesis. There are nine members of the PRMT family, which are divided into 4 types (types I-IV). Although most PRMTs do not require posttranslational modification (PTM) to be activated, fine-tuning modifications, such as interactions between cofactor proteins, subcellular compartmentalization, and regulation of RNA, via micro-RNAs, seem to be required...
2016: Mediators of Inflammation
Yu V Karpets, Yu E Kolupaev, T O Yastreb
The effects of functional interplay of calcium ions, reactive oxygen species (ROS) and nitric oxide (NO) in the cells of wheat plantlets roots (Triticum aestivum L.) at the induction of their heat resistance by a short-term influence of hyperthermia (heating at the temperature of 42 degrees C during 1 minute) have been investigated. The transitional increase of NO and H2O2 content, invoked by heating, was suppressed by the treatment of plantlets with the antagonists of calcium EGTA (chelator of exocellular calcium), lanthanum chloride (blocker of calcium channels of various types) and neomycin (inhibitor of phosphatidylinositol-dependent phospholipase C)...
November 2015: Ukrainian Biochemical Journal
Hui-Chen Lo, Ching-Yi Hung, Fu-Huan Huang, Tzu-Cheng Su, Chien-Hsing Lee
The combined treatment of parenteral arginine and the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) have been shown to improve liver function and systemic inflammation in subacute peritonitic rats. Here, we investigated the effects of single and combined parenteral arginine and L-NAME treatments on leukocyte and splenocyte immunity. Male Wistar rats were subjected to cecal punctures and were intravenously given total parenteral nutrition solutions with or without arginine and/or L-NAME supplementations for 7 days...
2016: PloS One
Hana A Itani, Liang Xiao, Mohamed A Saleh, Jing Wu, Mark A Pilkinton, Bethany L Dale, Natalia R Barbaro, Jason D Foss, Annet Kirabo, Kim R Montaniel, Allison E Norlander, Wei Chen, Ryosuke Sato, L Gabriel Navar, Simon A Mallal, Meena S Madhur, Kenneth E Bernstein, David G Harrison
RATIONALE: Accumulating evidence supports a role of adaptive immunity and particularly T cells in the pathogenesis of hypertension. Formation of memory T cells, which requires the costimulatory molecule CD70 on antigen-presenting cells, is a cardinal feature of adaptive immunity. OBJECTIVE: To test the hypothesis that CD70 and immunologic memory contribute to the blood pressure elevation and renal dysfunction mediated by repeated hypertensive challenges. METHODS AND RESULTS: We imposed repeated hypertensive challenges using either N(ω)-nitro-L-arginine methyl ester hydrochloride (L-NAME)/high salt or repeated angiotensin II stimulation in mice...
April 15, 2016: Circulation Research
V G Aleksandrov, N P Aleksandrova, T S Tumanova, A D Evseeva, V A Merkuriev
The role of NO-ergic mechanisms in the realization of the respiratory effects of pro-inflammatory cytokine IL-1beta was investigated in acute experiments on anesthetized rats. To achieve this, we studied the effect of intravenous administration of IL-1beta during inhibition of NO-synthase by N-nitro-L-arginine methyl ester (L-NAME, a non-specific blocker of NO-synthase) on the parameters of breathing and the Hering-Breuer inspiratory-inhibitory reflex. It was shown that the effect of L-NAME eliminates the IL-1beta-dependent increase of the Hering-Breuer reflex, whereas effects on breathing pattern does not change: the increase in IL-1beta system-level evokes an increase in respiratory rate, tidal volume and lung ventilation...
December 2015: Rossiĭskii Fiziologicheskiĭ Zhurnal Imeni I.M. Sechenova
L Scourzic, L Couronné, M T Pedersen, V Della Valle, M Diop, E Mylonas, J Calvo, E Mouly, C K Lopez, N Martin, M Fontenay, A Bender, S Guibert, P Dubreuil, P Dessen, N Droin, F Pflumio, M Weber, P Gaulard, K Helin, T Mercher, O A Bernard
TEN-ELEVEN-TRANSLOCATION-2 (TET2) and DNA-METHYLTRANSFERASE-3A (DNMT3A), both encoding proteins involved in regulating DNA methylation, are mutated in hematological malignancies affecting both myeloid and lymphoid lineages. We previously reported an association of TET2 and DNMT3A mutations in progenitors of patients with angioimmunoblastic T-cell lymphomas (AITL). Here, we report on the cooperative effect of Tet2 inactivation and DNMT3A mutation affecting arginine 882 (DNMT3A(R882H)) using a murine bone marrow transplantation assay...
June 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Kamal El Bissati, Elena S Suvorova, Hui Xiao, Olivier Lucas, Rajendra Upadhya, Yanfen Ma, Ruth Hogue Angeletti, Michael W White, Louis M Weiss, Kami Kim
UNLABELLED: The arginine methyltransferase family (PRMT) has been implicated in a variety of cellular processes, including signal transduction, epigenetic regulation, and DNA repair pathways. PRMT1 is thought to be responsible for the majority of PRMT activity in Toxoplasma gondii, but its exact function is unknown. To further define the biological function of the PRMT family, we generated T. gondii mutants lacking PRMT1 (Δprmt1) by deletion of the PRMT1 gene. Δprmt1 parasites exhibit morphological defects during cell division and grow slowly, and this phenotype reverses in the Δprmt::PRMT1mRFP complemented strain...
February 2, 2016: MBio
M P Greenwood, M Greenwood, B T Gillard, S Y Loh, J F R Paton, D Murphy
The synthesis of arginine vasopressin (AVP) in the supraoptic nucleus (SON) and paraventricular nucleus (PVN) of the hypothalamus is sensitive to increased plasma osmolality and a decreased blood volume, and thus is robustly increased by both dehydration (increased plasma osmolality and decreased blood volume) and salt loading (increased plasma osmolality). Both stimuli result in functional remodelling of the SON and PVN, a process referred to as functional-related plasticity. Such plastic changes in the brain have recently been associated with altered patterns of DNA methylation at CpG (cytosine-phosphate-guanine) residues, a process considered to be important for the regulation of gene transcription...
April 2016: Journal of Neuroendocrinology
William T Jorgensen, Damien W Gulliver, Eryn L Werry, Tristan Reekie, Mark Connor, Michael Kassiou
A previously identified, non-peptidic oxytocin (OT) receptor agonist WAY-267,464 (1) and nine novel derivatives (3, 4a-7a, 4b-7b) were synthesised and evaluated in vitro with the aim of systematically exploring hydrogen bonding interactions and ligand flexibility. All analogues were subjected to competition radioligand binding assays at human oxytocin (OT) and arginine vasopressin 1a (V1a) receptors. Physiological activity was determined using whole cell IP1 accumulation assays. Under these conditions, WAY-267,464 had higher affinity for the V1a receptor compared to the OT receptor (8...
January 27, 2016: European Journal of Medicinal Chemistry
Joshua P Owings, Emily G Kuiper, Samantha M Prezioso, Jeffrey Meisner, John J Varga, Natalia Zelinskaya, Eric B Dammer, Duc M Duong, Nicholas T Seyfried, Sebastián Albertí, Graeme L Conn, Joanna B Goldberg
Pseudomonas aeruginosa is a Gram-negative opportunistic pathogen that trimethylates elongation factor-thermo-unstable (EF-Tu) on lysine 5. Lysine 5 methylation occurs in a temperature-dependent manner and is generally only seen when P. aeruginosa is grown at temperatures close to ambient (25 °C) but not at higher temperatures (37 °C). We have previously identified the gene, eftM (for EF-Tu-modifying enzyme), responsible for this modification and shown its activity to be associated with increased bacterial adhesion to and invasion of respiratory epithelial cells...
February 12, 2016: Journal of Biological Chemistry
Laurensia Yuniati, Laurens T van der Meer, Esther Tijchon, Dorette van Ingen Schenau, Liesbeth van Emst, Marloes Levers, Sander A L Palit, Caroline Rodenbach, Geert Poelmans, Peter M Hoogerbrugge, Jixiu Shan, Michael S Kilberg, Blanca Scheijen, Frank N van Leeuwen
Cancer cells are frequently exposed to physiological stress conditions such as hypoxia and nutrient limitation. Escape from stress-induced apoptosis is one of the mechanisms used by malignant cells to survive unfavorable conditions. B-cell Translocation Gene 1 (BTG1) is a tumor suppressor that is frequently deleted in acute lymphoblastic leukemia and recurrently mutated in diffuse large B cell lymphoma. Moreover, low BTG1 expression levels have been linked to poor outcome in several solid tumors. How loss of BTG1 function contributes to tumor progression is not well understood...
January 19, 2016: Oncotarget
Yinpu Yue, Wei Huang, Jingjing Liang, Jing Guo, Jian Ji, Yunliang Yao, Mingzhu Zheng, Zhijian Cai, Linrong Lu, Jianli Wang
Interleukin 4-induced gene-1 (IL4I1) was initially described as an early IL-4-inducible gene in B cells. IL4I1 protein can inhibit T cell proliferation by releasing its enzymatic catabolite, H2O2, and this effect is associated with transient down-regulation of T cell CD3 receptor-zeta (TCRζ) expression. Herein, we show that IL4I1 contributes to the regulation of macrophage programming. We found that expression of IL4I1 increased during bone marrow-derived macrophage (BMDM) differentiation, expression of IL4I1 is much higher in primary macrophages than monocytes, and IL4I1 expression in BMDMs could be induced by Th1 and Th2 cytokines in two different patterns...
2015: PloS One
Hsin-Wei Liao, Jung-Mao Hsu, Weiya Xia, Hung-Ling Wang, Ying-Nai Wang, Wei-Chao Chang, Stefan T Arold, Chao-Kai Chou, Pei-Hsiang Tsou, Hirohito Yamaguchi, Yueh-Fu Fang, Hong-Jen Lee, Heng-Huan Lee, Shyh-Kuan Tai, Mhu-Hwa Yang, Maria P Morelli, Malabika Sen, John E Ladbury, Chung-Hsuan Chen, Jennifer R Grandis, Scott Kopetz, Mien-Chie Hung
Posttranslational modifications to the intracellular domain of the EGFR are known to regulate EGFR functions; however, modifications to the extracellular domain and their effects remain relatively unexplored. Here, we determined that methylation at R198 and R200 of the EGFR extracellular domain by protein arginine methyltransferase 1 (PRMT1) enhances binding to EGF and subsequent receptor dimerization and signaling activation. In a mouse orthotopic colorectal cancer xenograft model, expression of a methylation-defective EGFR reduced tumor growth...
December 2015: Journal of Clinical Investigation
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