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Methyltransferase

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https://www.readbyqxmd.com/read/28319045/akt-mediated-stabilization-of-histone-methyltransferase-whsc1-promotes-prostate-cancer-metastasis
#1
Ni Li, Wei Xue, Huairui Yuan, Baijun Dong, Yufeng Ding, Yongfeng Liu, Min Jiang, Shan Kan, Tongyu Sun, Jiale Ren, Qiang Pan, Xiang Li, Peiyuan Zhang, Guohong Hu, Yan Wang, Xiaoming Wang, Qintong Li, Jun Qin
Loss of phosphatase and tensin homolog (PTEN) and activation of the PI3K/AKT signaling pathway are hallmarks of prostate cancer (PCa). However, these alterations alone are insufficient for cells to acquire metastatic traits. Here, we have shown that the histone dimethyl transferase WHSC1 critically drives indolent PTEN-null tumors to become metastatic PCa. In a PTEN-null murine PCa model, WHSC1 overexpression in prostate epithelium cooperated with Pten deletion to produce a metastasis-prone tumor. Conversely, genetic ablation of Whsc1 prevented tumor progression in PTEN-null mice...
March 20, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28318634/dna-methyltransferase-1-may-be-a-therapy-target-for-attenuating-diabetic-nephropathy-and-podocyte-injury
#2
Li Zhang, Qianmei Zhang, Shuangxin Liu, Yuanhan Chen, Ruizhao Li, Ting Lin, Chunping Yu, Hong Zhang, Zhongshun Huang, Xinchen Zhao, Xiaofan Tan, Zhuo Li, Zhiming Ye, Jianchao Ma, Bin Zhang, Wenjian Wang, Wei Shi, Xinling Liang
The contribution of DNA methylation to diabetic nephropathy, especially the effect on podocyte integrity, is not clarified. Here we found that albuminuria in a db/db mouse model was markedly attenuated after treatment with a DNA methylation inhibitor. This was accompanied by alleviation of glomerular hypertrophy, mesangial matrix expansion, and podocyte injury. The expression of DNA methyltransferase 1 (Dnmt1), nuclear factor Sp1, and nuclear factor kappa B (NFκB)-p65 markedly increased in podocytes in vivo and in vitro under the diabetic state...
March 15, 2017: Kidney International
https://www.readbyqxmd.com/read/28315782/human-comt-over-expression-confers-a-heightened-susceptibility-to-dyskinesia-in-mice
#3
Oscar Solís, Jose-Rubén García-Montes, Patricia Garcia-Sanz, Antonio S Herranz, Maria-José Asensio, Gina Kang, Noboru Hiroi, Rosario Moratalla
Catechol-O-methyltransferase (COMT) degrades dopamine and its precursor l-DOPA and plays a critical role in regulating synaptic dopamine actions. We investigated the effects of heightened levels of COMT on dopamine-regulated motor behaviors and molecular alterations in a mouse model of dyskinesia. Transgenic mice overexpressing human COMT (TG) and their wildtype (WT) littermates received unilateral 6-OHDA lesions in the dorsal striatum and were treated chronically with l-DOPA for two weeks. l-DOPA-induced dyskinesia was exacerbated in TG mice without altering l-DOPA motor efficacy as determined by contralateral rotations or motor coordination...
March 15, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28315733/wt1-ameliorates-podocyte-injury-via-repression-of-ezh2-%C3%AE-catenin-pathway-in-diabetic-nephropathy
#4
Jiao Wan, Xiaoyan Hou, Zhanmei Zhou, Jian Geng, Jianwei Tian, Jing Nie, Xiaoyan Bai
Epigenetic modulation of podocyte injury plays a pivotal role in diabetic nephropathy (DN). Wilm's tumor 1 (WT1) has been found to have opposing roles with β-catenin in podocyte biology. Herein, we asked whether the histone methyltransferase enzyme enhancer of zeste homolog 2 (EZH2) promotes WT1-induced podocyte injury via β-catenin activation and the underlying mechanisms. We found that WT1 antagonized EZH2 and ameliorated β-catenin-mediated podocyte injury as demonstrated by attenuated podocyte mesenchymal transition, maintenance of podocyte architectural integrity, decreased podocyte apoptosis and oxidative stress...
March 15, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28315332/nuclear-ampk-regulated-carm1-stabilization-impacts-autophagy-in-aged-heart
#5
Chen Li, Lu Yu, Han Xue, Zheng Yang, Yue Yin, Bo Zhang, Mai Chen, Heng Ma
Senescence-associated autophagy downregulation leads to cardiomyocyte dysfunction. Coactivator-associated arginine methyltransferase 1 (CARM1) participates in many cellular processes, including autophagy in mammals. However, the effect of CARM1 in aging-related cardiac autophagy decline remains undefined. Moreover, AMP-activated protein kinase (AMPK) is a key regulator in metabolism and autophagy, however, the role of nuclear AMPK in autophagy outcome in aged hearts still unclear. Hers we identify the correlation between nuclear AMPK and CARM1 in aging heart...
March 15, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28314628/petit-high-pressure-carbon-dioxide-stress-increases-synthesis-of-s-adenosylmethionine-and-phosphatidylcholine-in-yeast-saccharomyces-cerevisiae
#6
Liyuan Niu, Kazuki Nomura, Hitoshi Iwahashi, Hiroyuki Matsuoka, Satoshi Kawachi, Yoshihisa Suzuki, Katsuhiro Tamura
Petit-High Pressure Carbon Dioxide (p-HPCD) is a promising nonthermal technology for foods pasteurization. Cluster analysis of gene expression profiles of Saccharomyces cerevisiae exposed to various stresses exhibited that gene expression profile for p-HPCD stress (0.5MPa, 25°C) was grouped into a cluster including profiles for Sodium Dodecyl Sulfate and Roundup herbicide. Both are detergents that can disorder membrane structurally and functionally, which suggests that cell membrane may be a target of p-HPCD stress to cause cell growth inhibition...
March 8, 2017: Biophysical Chemistry
https://www.readbyqxmd.com/read/28314386/veliparib-in-combination-with-radiotherapy-for-the-treatment-of-mgmt-unmethylated-glioblastoma
#7
Toni Rose Jue, Kyoko Nozue, Ashleigh J Lester, Swapna Joshi, Lisette B W Schroder, Shane P Whittaker, Sheri Nixdorf, Robert W Rapkins, Mustafa Khasraw, Kerrie L McDonald
BACKGROUND: The O (6) -methylguanine methyltransferase (MGMT) gene is frequently unmethylated in patients with glioblastoma (GBM), rendering them non-responsive to the standard treatment regime of surgery followed by concurrent radiotherapy (RT) and temozolomide. Here, we investigate the efficacy of adding a PARP inhibitor, veliparib, to radiotherapy to treat MGMT unmethylated GBM. METHODS: The inhibition of PARP with veliparib (ABT-888), a potent and orally bioavailable inhibitor in combination with RT was tested on a panel of patient derived cell lines (PDCLs) and patient-derived xenografts (PDX) models generated from GBM patients with MGMT unmethylated tumors...
March 17, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28314309/elevated-metabolic-activity-on-18-f-fdg-pet-ct-is-associated-with-the-expression-of-ezh2-in-non-small-cell-lung-cancer
#8
Gouji Toyokawa, Kazuki Takada, Tatsuro Okamoto, Yuka Kozuma, Taichi Matsubara, Naoki Haratake, Takaki Akamine, Shinkichi Takamori, Masakazu Katsura, Fumihiro Shoji, Ryuji Hamamoto, Yoshinao Oda, Yoshihiko Maehara
BACKGROUND/AIM: Enhancer of zeste homolog 2 (EZH2) is a histone methyltransferase that is deeply involved in the pathogenesis of lung cancer. We evaluated the metabolic characteristics of non-small cell lung cancer (NSCLC) in patients with and without expression of EZH2 using (18)F-fluorodeoxyglucose positron-emission tomography/ computed tomography ((18)F-FDG PET/CT). MATERIALS AND METHODS: The EZH2 protein expression of 268 patients with resected NSCLC, whose preoperative (18)F-FDG PET/CT information was available, was evaluated by immunohistochemistry with clone 6A10 antibody; cases with Allred score ≥3 were considered positive...
March 2017: Anticancer Research
https://www.readbyqxmd.com/read/28314286/safety-and-tolerance-of-d-l-methadone-in-combination-with-chemotherapy-in-patients-with-glioma
#9
Julia Onken, Claudia Friesen, Peter Vajkoczy, Martin Misch
BACKGROUND/AIM: D,L-Methadone increases sensitivity toward chemotherapy of different tumor cell populations. We evaluated the safety and tolerance of additional use of D,L-methadone in patients with glioma in combination with chemotherapy. PATIENTS AND METHODS: The dosage, duration of therapy and side-effects related to D,L-methadone were recorded in 27 patients. Toxicity was assessed accordingly to the Common Toxicity Criteria (CTC) of the National Cancer Institute...
March 2017: Anticancer Research
https://www.readbyqxmd.com/read/28306504/targeting-of-polycomb-repressive-complex-2-to-rna-by-short-repeats-of-consecutive-guanines
#10
Xueyin Wang, Karen J Goodrich, Anne R Gooding, Haroon Naeem, Stuart Archer, Richard D Paucek, Daniel T Youmans, Thomas R Cech, Chen Davidovich
Polycomb repressive complex 2 (PRC2) is a histone methyltransferase that trimethylates H3K27, a mark of repressed chromatin. Mammalian PRC2 binds RNA promiscuously, with thousands of target transcripts in vivo. But what does PRC2 recognize in these RNAs? Here we show that purified human PRC2 recognizes G > C,U ≫ A in single-stranded RNA and has a high affinity for folded guanine quadruplex (G4) structures but little binding to duplex RNAs. Importantly, G-tract motifs are significantly enriched among PRC2-binding transcripts in vivo...
March 16, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28303350/immunohistochemical-evaluation-of-klotho-and-dna-methyltransferase-3a-in-oral-squamous-cell-carcinomas
#11
Bhoj Raj Adhikari, Osamu Uehara, Hirofumi Matsuoka, Rie Takai, Fumiya Harada, Masafumi Utsunomiya, Takatoshi Chujo, Tetsuro Morikawa, Mamata Shakya, Koki Yoshida, Jun Sato, Toshiya Arakawa, Michiko Nishimura, Hiroki Nagayasu, Itsuo Chiba, Yoshihiro Abiko
Carcinoma follows a course of multiple changes that are affected by several important factors, with epigenetic silencing of the promoter gene being one of them. A series of studies have suggested that epigenetic changes in the anti-aging gene Klotho may be one of the emerging areas of concern in the study of carcinogenesis. We hypothesized that epigenetic silencing of Klotho due to hypermethylation of DNMT3a may be one of the causes of carcinoma in the oral and maxillofacial region. In this study, we analyzed the immunohistochemical expressions of Klotho and DNMT3a in tissues obtained from oral dysplasia and oral squamous cell carcinoma...
March 16, 2017: Medical Molecular Morphology
https://www.readbyqxmd.com/read/28302565/inhibition-of-prmt5-suppresses-osteoclast-differentiation-and-partially-protects-against-ovariectomy-induced-bone-loss-through-downregulation-of-cxcl10-and-rsad2
#12
Yonghui Dong, Chao Song, Yuting Wang, Zuowei Lei, Fei Xu, Hanfeng Guan, Anmin Chen, Feng Li
Protein arginine methyltransferase 5 (PRMT5) is an arginine methylation methyltransferase that regulates various physiological processes. Abnormal PRMT5 activity has been reported in inflammation and various types of cancers. Because osteoclast differentiation is characterized by the activation of inflammation-related pathways, we speculated that PRMT5 may play a role in this process. In the present study, we found that PRMT5 was upregulated during osteoclast differentiation. Knockdown of PRMT5 with siRNA in bone marrow mononuclear cells (BMMs) resulted in inhibition of receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast formation...
March 14, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28302063/epigenetic-and-genetic-alterations-and-their-influence-on-gene-regulation-in-chronic-lymphocytic-leukemia
#13
Di Huang, Ivan Ovcharenko
BACKGROUND: To understand the changes of gene regulation in carcinogenesis, we explored signals of DNA methylation - a stable epigenetic mark of gene regulatory elements - and designed a computational model to profile loss and gain of regulatory elements (REs) during carcinogenesis. We also utilized sequencing data to analyze the allele frequency of single nucleotide polymorphisms (SNPs) and detected the cancer-associated SNPs, i.e., the SNPs displaying the significant allele frequency difference between cancer and normal samples...
March 16, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28301607/green-tea-proanthocyanidins-cause-impairment-of-hormone-regulated-larval-development-and-reproductive-fitness-via-repression-of-juvenile-hormone-acid-methyltransferase-insulin-like-peptide-and-cytochrome-p450-genes-in-anopheles-gambiae-sensu-stricto
#14
Jackson M Muema, Steven G Nyanjom, James M Mutunga, Sospeter N Njeru, Joel L Bargul
Successful optimization of plant-derived compounds into control of nuisance insects would benefit from scientifically validated targets. However, the close association between the genotypic responses and physiological toxicity effects mediated by these compounds remains underexplored. In this study, we evaluated the sublethal dose effects of proanthocyanidins (PAs) sourced from green tea (Camellia sinensis) on life history traits of Anopheles gambiae (sensu stricto) mosquitoes with an aim to unravel the probable molecular targets...
2017: PloS One
https://www.readbyqxmd.com/read/28301528/genome-wide-mapping-of-histone-h3k9me2-in-acute-myeloid-leukemia-reveals-large-chromosomal-domains-associated-with-massive-gene-silencing-and-sites-of-genome-instability
#15
Anna C Salzberg, Abigail Harris-Becker, Evgenya Y Popova, Nikki Keasey, Thomas P Loughran, David F Claxton, Sergei A Grigoryev
A facultative heterochromatin mark, histone H3 lysine 9 dimethylation (H3K9me2), which is mediated by histone methyltransferases G9a/GLP (EHMT2/1), undergoes dramatic rearrangements during myeloid cell differentiation as observed by chromatin imaging. To determine whether these structural transitions also involve genomic repositioning of H3K9me2, we used ChIP-sequencing to map genome-wide topography of H3K9me2 in normal human granulocytes, normal CD34+ hematopoietic progenitors, primary myeloblasts from acute myeloid leukemia (AML) patients, and a model leukemia cell line K562...
2017: PloS One
https://www.readbyqxmd.com/read/28301308/regenerating-muscle-with-arginine-methylation
#16
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/28301141/reconstitution-and-substrate-specificity-of-the-radical-sam-thiazole-c-methyltransferase-in-thiomuracin-biosynthesis
#17
Nilkamal Mahanta, Zhengan Zhang, Graham A Hudson, Wilfred A van der Donk, Douglas A Mitchell
Thiomuracin is a thiopeptide antibiotic with potent activity towards Gram-positive drug-resistant bacteria. Thiomuracin is biosynthesized from a precursor peptide, TbtA, by a complex array of posttranslational modifications. One of several intriguing transformations is the C-methylation of thiazole, occurring at an unactivated sp2 carbon. Herein, we report the in vitro reconstitution of TbtI, the responsible radical S-adenosyl-methionine (rSAM) C-methyltransferase, which catalyzes the formation of 5-methylthiazole at a single site...
March 16, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28300471/decoupling-of-dna-methylation-and-activity-of-intergenic-line-1-promoters-in-colorectal-cancer
#18
Natasha Vafadar-Isfahani, Christina Parr, Lara E McMillan, Juliane Sanner, Zhao Yeo, Stephen Saddington, Oliver Peacock, Hazel A Cruickshanks, Richard R Meehan, Jonathan N Lund, Cristina Tufarelli
Hypomethylation of LINE-1 repeats in cancer has been proposed as the main mechanism behind their activation; this assumption, however, was based on findings from early studies that were biased towards young and transpositionally active elements. Here, we investigate the relationship between methylation of two intergenic, transpositionally inactive LINE-1 elements and expression of the LINE-1 chimeric transcript (LCT) 13 and LCT14 driven by their antisense promoters (L1-ASP). Our data from DNA modification, expression, and 5'RACE analyses suggest that colorectal cancer methylation in the regions analyzed is not always associated with LCT repression...
March 16, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28298550/limited-role-for-extended-maintenance-temozolomide-for-newly-diagnosed-glioblastoma
#19
Dorothee Gramatzki, Philipp Kickingereder, Bettina Hentschel, Jörg Felsberg, Ulrich Herrlinger, Gabriele Schackert, Jörg-Christian Tonn, Manfred Westphal, Michael Sabel, Uwe Schlegel, Wolfgang Wick, Torsten Pietsch, Guido Reifenberger, Markus Loeffler, Martin Bendszus, Michael Weller
OBJECTIVE: To explore an association with survival of modifying the current standard of care for patients with newly diagnosed glioblastoma of surgery followed by radiotherapy plus concurrent and 6 cycles of maintenance temozolomide chemotherapy (TMZ/RT → TMZ) by extending TMZ beyond 6 cycles. METHODS: The German Glioma Network cohort was screened for patients with newly diagnosed glioblastoma who received TMZ/RT → TMZ and completed ≥6 cycles of maintenance chemotherapy without progression...
March 15, 2017: Neurology
https://www.readbyqxmd.com/read/28298486/protein-arginine-methyltransferases-interact-with-ift-particles-and-change-location-during-flagellar-growth-and-resorption
#20
Katsutoshi Mizuno, Roger D Sloboda
Changes in protein activity driven by post translational modifications comprise an important mechanism for the control of many cellular processes. Several flagellar proteins are methylated on arginine residues during flagellar resorption; however, the function is not understood. To learn more about the role of protein methylation during flagellar dynamics, we have focused on protein arginine methyltransferases (PRMTs) 1, 3, 5, and 10. These PRMTs localize to the tip of flagella and in a punctate pattern along the length, very similar, but not identical, to that of intraflagellar transport (IFT) components...
March 15, 2017: Molecular Biology of the Cell
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