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Arginine methylation t cell

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https://www.readbyqxmd.com/read/29651020/gfi1-facilitates-efficient-dna-repair-by-regulating-prmt1-dependent-methylation-of-mre11-and-53bp1
#1
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/29626090/a-gtpase-activating-protein-binding-protein-g3bp1-antiviral-protein-relay-conveys-arteriosclerotic-wnt-signals-in-aortic-smooth-muscle-cells
#2
Bindu Ramachandran, John N Stabley, Su-Li Cheng, Abraham S Behrmann, Austin Gay, Li Li, Megan Mead, Julia Kozlitina, Andrew Lemoff, Hamid Mirzaei, Zhijian Chen, Dwight A Towler
In aortic vascular smooth muscle (VSM), the canonical Wnt receptor LRP6 inhibits protein arginine (Arg) methylation, a new component of noncanonical Wnt signaling that stimulates nuclear factor of activated T cells (viz., NFATc4). To better understand how methylation mediates these actions, mass spectrometry was performed on VSM cell extracts from control and LRP6-deficient mice. LRP6-dependent Arg methylation was regulated on > 500 proteins; only 21 exhibited increased monomethylation (MMA) with concomitant reductions in dimethylation...
April 6, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29501774/protein-arginine-methyltransferase-5-mediates-enolase-1-cell-surface-trafficking-in-human-lung-adenocarcinoma-cells
#3
Dariusz Zakrzewicz, Miroslava Didiasova, Marcus Krüger, Benedetto Daniele Giaimo, Tilman Borggrefe, Maren Mieth, Andreas C Hocke, Anna Zakrzewicz, Liliana Schaefer, Klaus T Preissner, Malgorzata Wygrecka
OBJECTIVES: Enolase-1-dependent cell surface proteolysis plays an important role in cell invasion. Although enolase-1 (Eno-1), a glycolytic enzyme, has been found on the surface of various cells, the mechanism responsible for its exteriorization remains elusive. Here, we investigated the involvement of post-translational modifications (PTMs) of Eno-1 in its lipopolysaccharide (LPS)-triggered trafficking to the cell surface. RESULTS: We found that stimulation of human lung adenocarcinoma cells with LPS triggered the monomethylation of arginine 50 (R50me) within Eno-1...
March 1, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29476751/evidence-of-a-role-for-spinal-hmgb1-in-ischemic-stress-induced-mechanical-allodynia-in-mice
#4
Wataru Matsuura, Shinichi Harada, Keyue Liu, Masahiro Nishibori, Shogo Tokuyama
We have previously showed that spinal high-mobility group box-1 (HMGB1) plays an important role in the induction of central post-stroke pain (CPSP). It has been reported that HMGB1 exacerbates inflammation and pain via TLR4 or RAGE. Furthermore, the relationship between glial cells, such as microglia and astrocytes, involved in pain exacerbation and HMGB1 has also attracted attention. In this study, we investigated whether the interaction between spinal glial cells and HMGB1 signaling, including its receptors TLR4 or RAGE, is directly involved in the induction of CPSP...
February 21, 2018: Brain Research
https://www.readbyqxmd.com/read/29420098/smad6-methylation-represses-nf%C3%AE%C2%BAb-activation-and-periodontal-inflammation
#5
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/29113301/ucp2-and-prmt1-are-key-prognostic-markers-for-lung-carcinoma-patients
#6
Corina T Madreiter-Sokolowski, Balázs Győrffy, Christiane Klec, Armin A Sokolowski, Rene Rost, Markus Waldeck-Weiermair, Roland Malli, Wolfgang F Graier
Cancer cells have developed unique strategies to meet their high energy demand. Therefore, they have established a setting of Ca(2+)-triggered high mitochondrial activity. But mitochondrial Ca(2+) uptake has to be strictly controlled to avoid mitochondrial Ca(2+) overload that would cause apoptotic cell death. Methylation by protein arginine methyl transferase 1 (PRMT1) desensitizes the mitochondrial Ca(2+) uptake machinery and reduces mitochondrial Ca(2+) accumulation in cancer cells. In case of PRMT1-driven methylation, proper mitochondrial Ca(2+) uptake is reestablished by increased activity of uncoupling protein 2 (UCP2), pointing to an importance of these proteins for cancer cell survival and activity...
October 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/29026071/arginine-methylation-catalyzed-by-prmt1-is-required-for-b-cell-activation-and-differentiation
#7
Simona Infantino, Amanda Light, Kristy O'Donnell, Vanessa Bryant, Danielle T Avery, Michael Elliott, Stuart G Tangye, Gabrielle Belz, Fabienne Mackay, Stephane Richard, David Tarlinton
Arginine methylation catalyzed by protein arginine methyltransferases (PRMT) is a common post-translational modification in mammalian cells, regulating many important functions including cell signalling, proliferation and differentiation. Here we show the role of PRMT1 in B-cell activation and differentiation. PRMT1 expression and activity in human and mouse peripheral B cells increases in response to in vitro or in vivo activation. Deletion of the Prmt1 gene in mature B cells establishes that although the frequency and phenotype of peripheral B cell subsets seem unaffected, immune responses to T-cell-dependent and -independent antigens are substantially reduced...
October 12, 2017: Nature Communications
https://www.readbyqxmd.com/read/28986316/presence-of-a-consensus-dna-motif-at-nearby-dna-sequence-of-the-mutation-susceptible-cg-nucleotides
#8
Kaushik Chowdhury, Suresh Kumar, Tanu Sharma, Ankit Sharma, Meenakshi Bhagat, Asangla Kamai, Bridget M Ford, Shailendra Asthana, Chandi C Mandal
Complexity in tissues affected by cancer arises from somatic mutations and epigenetic modifications in the genome. The mutation susceptible hotspots present within the genome indicate a non-random nature and/or a position specific selection of mutation. An association exists between the occurrence of mutations and epigenetic DNA methylation. This study is primarily aimed at determining mutation status, and identifying a signature for predicting mutation prone zones of tumor suppressor (TS) genes. Nearby sequences from the top five positions having a higher mutation frequency in each gene of 42 TS genes were selected from a cosmic database and were considered as mutation prone zones...
January 10, 2018: Gene
https://www.readbyqxmd.com/read/28977470/the-prmt5-wdr77-complex-regulates-alternative-splicing-through-znf326-in-breast-cancer
#9
Madhumitha Rengasamy, Fan Zhang, Ajay Vashisht, Won-Min Song, Francesca Aguilo, Yifei Sun, SiDe Li, Weijia Zhang, Bin Zhang, James A Wohlschlegel, Martin J Walsh
We observed overexpression and increased intra-nuclear accumulation of the PRMT5/WDR77 in breast cancer cell lines relative to immortalized breast epithelial cells. Utilizing mass spectrometry and biochemistry approaches we identified the Zn-finger protein ZNF326, as a novel interaction partner and substrate of the nuclear PRMT5/WDR77 complex. ZNF326 is symmetrically dimethylated at arginine 175 (R175) and this modification is lost in a PRMT5 and WDR77-dependent manner. Loss of PRMT5 or WDR77 in MDA-MB-231 cells leads to defects in alternative splicing, including inclusion of A-T rich exons in target genes, a phenomenon that has previously been observed upon loss of ZNF326...
November 2, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28771838/human-regulatory-macrophages-are-potent-in-suppression-of-the-xenoimmune-response-via-indoleamine-2-3-dioxygenase-involved-mechanism-s
#10
Fei Guo, Min Hu, Dandan Huang, Yuanfei Zhao, Benjamin Heng, Gilles Guillemin, Chai K Lim, Wayne J Hawthorne, Shounan Yi
BACKGROUND: For xenotransplantation to truly succeed, we must develop immunomodulatory strategies to suppress the xenoimmune response but by minimizing immunosuppression over the long term. Regulatory macrophages (Mreg) have been shown to suppress polyclonal T-cell proliferation in vitro and prolong allograft survival in vivo. However, the question of whether they are capable of suppressing xenoimmune responses remains unknown. This study assessed the potential of human Mreg to be used as an effective immunomodulatory method in xenotransplantation...
August 2, 2017: Xenotransplantation
https://www.readbyqxmd.com/read/28637181/crosstalk-between-histone-modifications-indicates-that-inhibition-of-arginine-methyltransferase-carm1-activity-reverses-hiv-latency
#11
Zheng Zhang, Bryan C Nikolai, Leah A Gates, Sung Yun Jung, Edward B Siwak, Bin He, Andrew P Rice, Bert W O'Malley, Qin Feng
In eukaryotic cells, the gene expression status is strictly controlled by epigenetic modifications on chromatin. The repressive status of chromatin largely contributes to HIV latency. Studies have shown that modification of histone H3K27 acts as a key molecular switch for activation or suppression of many cellular genes. In this study, we found that K27-acetylated histone H3 specifically recruited Super Elongation Complex (SEC), the transcriptional elongation complex essential for HIV-1 long terminal repeat (LTR)-mediated and general cellular transcription...
September 19, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28588584/protein-arginine-methyltransferase-5-inhibition-upregulates-foxp3-regulatory-t-cells-frequency-and-function-during-the-ulcerative-colitis
#12
Yingxia Zheng, Liya Huang, Wensong Ge, Ming Yang, Yanhui Ma, Guohua Xie, Weiwei Wang, Bingxian Bian, Li Li, Hong Nie, Lisong Shen
Ulcerative colitis (UC) pathogenesis is related to imbalance of immune responses, and the equilibrium between inflammatory T cells and Foxp3(+) regulatory T cells (Tregs) plays an important role in the intestinal homeostasis. Protein arginine methyltransferases (PRMTs) regulate chromatin remodeling and gene expression. Here, we investigated whether inhibition of PRMTs affects colitis pathogenesis in mice and inflammatory bowel disease patients and further explored the underlying mechanisms. In this study, we found that protein arginine N-methyltransferase inhibitor 1 (AMI-1) treatments increased Tregs frequency, function, and reduced colitis incidence...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28587176/bifunctional-enzyme-jmjd6-contributes-to-multiple-disease-pathogenesis-new-twist-on-the-old-story
#13
REVIEW
Shiva Shankar Vangimalla, Murali Ganesan, Kusum K Kharbanda, Natalia A Osna
Jumonji domain-containing protein 6 (JMJD6) is a non-heme Fe(II) 2-oxoglutarate (2OG)-dependent oxygenase with arginine demethylase and lysyl hydroxylase activities. Its initial discovery as a dispensable phosphatidylserine receptor (PSR) in the cell membrane of macrophages for phagocytosis was squashed by newer studies which revealed its nuclear localization and bifunctional enzymatic activity. Though its interaction with several nuclear and cytoplasmic target proteins has been demonstrated, the exact mechanisms and clinical significance of these various biologic interplays are not yet well established...
June 1, 2017: Biomolecules
https://www.readbyqxmd.com/read/28582843/acute-lymphoblastic-leukemia-and-genetic-variations-in-bhmt-gene-case-control-study-and-computational-characterization
#14
Ravishankara Bellampalli, Manik Vohra, Kashish Sharma, Nalini Bhaskaranand, Kamalakshi G Bhat, Krishna Prasad, Anu R Sharma, Kapaettu Satyamoorthy, Padmalatha S Rai
BACKGROUND: Remethylation of homocysteine is catalyzed by B12 dependent methionine synthase (MTR) in all types of cells and by B12 non-dependent betaine homocysteine methyltransferase (BHMT) in liver and kidney cells. Of many etiologies of cancer, an unexplored area is the variations of genes implicated in methylation reaction. OBJECTIVE: The study evaluated the association of BHMT (rs3733890) with acute lymphoblastic leukemia (ALL), followed by in-silico characterization of variations in BHMT gene...
July 4, 2017: Cancer Biomarkers: Section A of Disease Markers
https://www.readbyqxmd.com/read/28542722/a-homozygous-potentially-pathogenic-variant-in-the-paxbp1-gene-in-a-large-family-with-global-developmental-delay-and-myopathic-hypotonia
#15
E Alharby, A M Albalawi, A Nasir, S A Alhijji, A Mahmood, K Ramzan, F Abdusamad, A Aljohani, O Abdelsalam, A Eldardear, S Basit
PAX binding protein 1 (PAXBP1) is an adaptor protein linking the transcription factor PAX3 and PAX7 to the histone methylation machinery. PAXBP1 is a nuclear protein and its high expression is known in brain cerebellar hemisphere and cerebellum. Moreover, it is also found in abundance in muscle precursor cells that are involved in myogenesis and skeletal muscles formation. Whole genome SNP genotyping and exome sequencing in a family with distinct syndrome of global developmental delay and hypotonia mapped the disease locus to the chromosome 21q22...
May 19, 2017: Clinical Genetics
https://www.readbyqxmd.com/read/28523359/arginine-cga-codons-as-a-source-of-nonsense-mutations-a-possible-role-in-multivariant-gene-expression-control-of-mrna-quality-and-aging
#16
Georgy A Romanov, Victor S Sukhoverov
Methylation of cytosine residues in DNA of higher eukaryotes, including humans, creates "hot spots" of C→T transitions in the genome. The predominantly methylated sequence in mammalian DNAs is CG (CpG). Among CG-containing codons, CGA codons for arginine are unique due to their ability to create stop codons TGA (UGA in mRNA) upon epigenetic-mediated mutation. As such nonsense mutations can have a strong adverse effect on the cell and organism, we have performed a study, on the example of human genes, aimed to characterise the anticipated effects of epigenetic-mediated nonsense mutations CGA→TGA in somatic cells...
May 18, 2017: Molecular Genetics and Genomics: MGG
https://www.readbyqxmd.com/read/28488390/mesenchymal-stem-cells-protect-from-acute-liver-injury-by-attenuating-hepatotoxicity-of-liver-nkt-cells-in-inos-and-ido-dependent-manner
#17
Marina Gazdic, Bojana Simovic Markovic, Ljubica Vucicevic, Tamara Nikolic, Valentin Djonov, Nebojsa Arsenijevic, Vladimir Trajkovic, Miodrag L Lukic, Vladislav Volarevic
The effects of mesenchymal stem cells (MSCs) on phenotype and function of natural killer T (NKT) cells, is not understood. We used concanavalin A (ConA) - and α-galactosylceramide (α-GalCer)-induced liver injury to evaluate effects of MSCs on NKT-dependent hepatotoxicity. Mouse MSCs (mMSCs) significantly reduced Con A- and α-GalCer-mediated hepatitis in C57Bl/6 mice, as demonstrated by histopathological and biochemical analysis, attenuated influx of inflammatory (T-bet(+) TNF-α, IFN-γ producing and GATA3(+) , IL-4-producing) liver NKT cells and down-regulated TNF-α, IFN-γ and IL-4 levels in the sera...
May 9, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/28487700/l-arginine-dependent-epigenetic-regulation-of-interleukin-10-but-not-transforming-growth-factor-%C3%AE-production-by-neonatal-regulatory-t-lymphocytes
#18
Hong-Ren Yu, Ching-Chang Tsai, Ling-Sai Chang, Hsin-Chun Huang, Hsin-Hsin Cheng, Jiu-Yao Wang, Jiunn-Ming Sheen, Ho-Chang Kuo, Kai-Sheng Hsieh, Ying-Hsien Huang, Kuender D Yang, Te-Yao Hsu
A growing number of diseases in humans, including trauma, certain cancers, and infection, are known to be associated with l-arginine deficiency. In addition, l-arginine must be supplemented by diet during pregnancy to aid fetal development. In conditions of l-arginine depletion, T cell proliferation is impaired. We have previously shown that neonatal blood has lower l-arginine levels than adult blood, which is associated with poor neonatal lymphocyte proliferation, and that l-arginine enhances neonatal lymphocyte proliferation through an interleukin (IL)-2-independent pathway...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28478950/emerging-role-for-methylation-in-multiple-sclerosis-beyond-dna
#19
REVIEW
Lindsay M Webb, Mireia Guerau-de-Arellano
Multiple Sclerosis (MS) is a chronic inflammatory disease of the central nervous system. The inflammatory and neurodegenerative pathways driving MS are modulated by DNA, lysine, and arginine methylation, as evidenced by studies made possible by novel tools for methylation detection or loss of function. We present evidence that MS is associated with genetic variants and metabolic changes that impact on methylation. Further, we comprehensively review current understanding of how methylation can impact on central nervous system (CNS) resilience and neuroregenerative potential, as well as inflammatory versus regulatory T helper (Th) cell balance...
June 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28454271/intracellular-and-extracellular-factors-influencing-the-genotoxicity-of-nitric-oxide-and-reactive-oxygen-species
#20
Min Young Kim
A number of factors affect cellular responses to nitric oxide (NO(•)) and reactive oxygen species (ROS), including their source, concentration, cumulative dose, target gene and biological milieu. This limits the extrapolation of data to in vivo pathological states in which NO(•) and ROS may be important. The present study investigated lethality and mutagenesis in the HPRT and TK1 genes of human lymphoblastoid TK6 cells exposed to NO(•) and ROS derived from two delivery methods: A reactor system and a Transwell™ co-culture...
March 2017: Oncology Letters
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