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https://www.readbyqxmd.com/read/28931237/histone-methyltransferase-set8-epigenetically-reprograms-host-immune-responses-to-assist-mycobacterial-survival
#1
Vikas Singh, Praveen Prakhar, R S Rajmani, Kasturi Mahadik, Salik Miskat Borbora, Kithiganahalli Narayanaswamy Balaji
NQO1 and TRXR1 are important host reductases implicated in the regulation of inflammation and apoptosis. Although the transcriptional machinery governing these processes have been extensively investigated, the associated epigenetic regulatory events remain unclear. Here, we report that SET8, a histone H4 lysine 20 monomethylase (H4K20me1), is highly induced during Mycobacterium tuberculosis infection that orchestrates immune evasion strategies through the induction of NQO1 and TRXR1 in vivo. SET8, along with FoxO3a, mediates an active NQO1-PGC1-α complex, which promotes the anti-inflammatory M2 macrophage phenotype, and assists TRXR1-regulated arrest of tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis...
August 15, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28931080/low-serum-level-of-mir-485-3p-predicts-poor-survival-in-patients-with-glioblastoma
#2
Zhi-Qiang Wang, Mei-Yin Zhang, Mei-Ling Deng, Nuo-Qing Weng, Hui-Yun Wang, Shao-Xiong Wu
MicroRNAs (miRNAs) are short noncoding RNAs that play critical roles in human malignancies and can be used as biomarkers for cancer. Until now, a number of biomarkers for prognosis of glioblastoma (GBM) have been reported in tumor tissues but only a few biomarkers in circulating fluid. Using a custom microarray, we previously identified 19 differentially expressed miRNAs in serum of patients with GBM. In this study, we investigated whether 3 of the 19 miRNAs in serum could be used as prognostic biomarkers for patients with GBM...
2017: PloS One
https://www.readbyqxmd.com/read/28930672/histone-h3-methylated-at-arginine-17-is-essential-for-reprogramming-the-paternal-genome-in-zygotes
#3
Yuki Hatanaka, Takeshi Tsusaka, Natsumi Shimizu, Kohtaro Morita, Takehiro Suzuki, Shinichi Machida, Manabu Satoh, Arata Honda, Michiko Hirose, Satoshi Kamimura, Narumi Ogonuki, Toshinobu Nakamura, Kimiko Inoue, Yoshihiko Hosoi, Naoshi Dohmae, Toru Nakano, Hitoshi Kurumizaka, Kazuya Matsumoto, Yoichi Shinkai, Atsuo Ogura
At fertilization, the paternal genome undergoes extensive reprogramming through protamine-histone exchange and active DNA demethylation, but only a few maternal factors have been defined in these processes. We identified maternal Mettl23 as a protein arginine methyltransferase (PRMT), which most likely catalyzes the asymmetric dimethylation of histone H3R17 (H3R17me2a), as indicated by in vitro assays and treatment with TBBD, an H3R17 PRMT inhibitor. Maternal histone H3.3, which is essential for paternal nucleosomal assembly, is unable to be incorporated into the male pronucleus when it lacks R17me2a...
September 19, 2017: Cell Reports
https://www.readbyqxmd.com/read/28930162/lean-body-mass-harbors-sensing-mechanisms-that-allow-safeguarding-of-methionine-homeostasis
#4
REVIEW
Yves Ingenbleek
Protein-depleted states generate allosteric inhibition of liver cystathionine β-synthase (CBS), which governs the first enzymatic step of the transsulfuration cascade, resulting in upstream accretion of homocysteine (Hcy) in body fluids. A similar Hcy increase may arise from normal hepatocytes undergoing experimentally-induced impairment of betaine-homocysteine methyltransferase (BHTM) activity or from components of lean body mass (LBM) submitted to any inflammatory disorder. LBM comprises a composite agglomeration of extrarenal tissues characterized by naturally occurring BHTM inactivity...
September 20, 2017: Nutrients
https://www.readbyqxmd.com/read/28929213/to-finish-things-well-cysteine-methylation-ensures-selective-gtpase-membrane-localization-and-signalling
#5
REVIEW
José Cansado
Isoprenylcysteine-O-Carboxyl Methyltransferase (ICMT) catalyzes the final step in the prenylation process of different proteins including members of the Ras superfamily of GTPases. While cysteine methylation is essential in mammalian cells for growth, membrane association, and signalling by Ras and Rho GTPases, its role during signal transduction events in simple eukaryotes like yeasts appears irrelevant. By using a multidisciplinary approach our group has recently shown that, contrary to this initial assumption, in the fission yeast Schizosaccharomyces pombe ICMT activity encoded by the Mam4 gene is not only important to promote selective plasma membrane targeting of Ras and specific Rho GTPases, but also to allow precise downstream signalling to the mitogen-activated protein kinase and target of rapamycin pathways in response to diverse environmental cues...
September 19, 2017: Current Genetics
https://www.readbyqxmd.com/read/28928973/prospective-replication-study-implicates-the-catechol-o-methyltransferase-val-158-met-polymorphism-as-a-biomarker-for-the-response-to-morphine-in-patients-with-cancer
#6
Hiromichi Matsuoka, Chihiro Makimura, Atsuko Koyama, Yoshihiko Fujita, Junji Tsurutani, Kiyohiro Sakai, Ryo Sakamoto, Kazuto Nishio, Kazuhiko Nakagawa
Genetic differences in humans cause clinical difficulties in opioid treatment. Previous studies indicate that a single nucleotide polymorphism in the catechol-O-methyltransferase (COMT) gene (rs4680; p.Val(158)Met) may present as a predictive biomarker for the response to morphine treatment. In our previous pilot exploratory study, patients with a G/G genotype were demonstrated to require a higher dose of morphine, compared with patients with A/A and A/G genotypes. In the present study, the aim was to replicate the findings in an independent cohort of opioid-treatment-naïve patients exhibiting various types of cancer...
October 2017: Biomedical Reports
https://www.readbyqxmd.com/read/28928282/dnmt1-dependent-chk1-pathway-suppression-is-protective-against-neuron-division
#7
Mio Oshikawa, Kei Okada, Hidenori Tabata, Koh-Ichi Nagata, Itsuki Ajioka
Neuronal differentiation and cell-cycle exit are tightly coordinated, even in pathological situations. When pathological neurons re-enter the cell cycle and progress through the S phase, they undergo cell death instead of division. However, the mechanisms underlying mitotic resistance are mostly unknown. Here, we have found that acute inactivation of retinoblastoma (Rb) family proteins (Rb, p107 and p130) in mouse postmitotic neurons leads to cell death after S-phase progression. Checkpoint kinase 1 (Chk1) pathway activation during the S phase prevented the cell death, and allowed the division of cortical neurons that had undergone acute Rb family inactivation, oxygen-glucose deprivation (OGD) or in vivo hypoxia-ischemia...
September 15, 2017: Development
https://www.readbyqxmd.com/read/28928088/20-s-ginsenoside-rh2-suppresses-proliferation-and-migration-of-hepatocellular-carcinoma-cells-by-targeting-ezh2-to-regulate-cdkn2a-2b-gene-cluster-transcription
#8
Qi Li, Bai Li, Chengya Dong, Yajie Wang, Qi Li
20(S)-Ginsenoside Rh2 (20(S)-GRh2) exerts important pharmacological effects with regard to the control of human hepatocellular carcinoma (HCC). EZH2 is a potent histone methyltransferase of H3K27me(3), which has been determined as an oncogene in many malignancies. The CDKN2A-2B gene cluster encodes three important tumor suppressors, P14, P15 and P16. In this study, the anticancer effect and molecular mechanism of 20(S)-GRh2 on HCC was investigated. Treatment of HCC cells with 20(S)-GRh2 inhibited cell proliferation, migration and induced cell cycle arrest at the G0/G1 phase, and inhibited tumor growth in vivo...
September 16, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28927791/design-and-synthesis-of-novel-prmt1-inhibitors-and-investigation-of-their-binding-preferences-using-molecular-modelling
#9
Hao Yang, Yifan Ouyang, Hao Ma, Hui Cong, Chunlin Zhuang, Wun-Taai Lok, Zhe Wang, Xuanli Zhu, Yutong Sun, Wei Hong, Hao Wang
Protein arginine methyltransferase 1 (PRMT1) catalyses the methylation of substrate arginine by transferring the methyl group from SAM (S-adenosyl-l-methionine), which leads to the formation of S-adenosyl homocysteine (SAH) and methylated arginine. We have shown previously that the Asp84 on PRMT1 could be a potential inhibitor binding site. In the current study, 28 compounds were designed and synthesized that were predicted to bind the Asp84 and substrate arginine sites together. Among them, 6 compounds were identified as potential PRMT1 inhibitors, and showed strong inhibitory effects on cancer cell lines, especially HepG2...
September 8, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28927461/additional-sex-combs-interacts-with-enhancer-of-zeste-and-trithorax-and-modulates-levels-of-trimethylation-on-histone-h3k4-and-h3k27-during-transcription-of-hsp70
#10
Taosui Li, Jacob W Hodgson, Svetlana Petruk, Alexander Mazo, Hugh W Brock
BACKGROUND: Maintenance of cell fate determination requires the Polycomb group for repression; the trithorax group for gene activation; and the enhancer of trithorax and Polycomb (ETP) group for both repression and activation. Additional sex combs (Asx) is a genetically identified ETP for the Hox loci, but the molecular basis of its dual function is unclear. RESULTS: We show that in vitro, Asx binds directly to the SET domains of the histone methyltransferases (HMT) enhancer of zeste [E(z)] (H3K27me3) and Trx (H3K4me3) through a bipartite interaction site separated by 846 amino acid residues...
September 19, 2017: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/28927055/silencing-dna-methyltransferase-1-leads-to-the-activation-of-the-esophageal-suppressor-gene-p16-in-vitro-and-in-vivo
#11
Jian Bai, Xue Zhang, Bangqing Liu, Haiyong Wang, Zhenzong Du, Jianfei Song
Previous studies have demonstrated that DNA methyltransferase 1 (DNMT1) is required for the maintenance of DNA methylation and epigenetic changes that may lead to the development of esophageal squamous cell carcinoma (ESCC). In order to investigate whether the silencing of DNMT1 protects tumor suppressor genes, including p16, and is able to be used as a potential therapy for human ESCC, short hairpin RNA targeting DNMT1 (shRNA-DNMT1) was synthesized and transfected into the human ESCC lines KYSE150 and KYSE410, which were then injected into the backs of nude mice prior to harvesting...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28926430/targeting-histone-methylation-in-cancer
#12
Michael T McCabe, Helai P Mohammad, Olena Barbash, Ryan G Kruger
Most, if not all, human cancers exhibit altered epigenetic signatures that promote aberrant gene expression that contributes to cellular transformation. Historically, attempts to pharmacologically intervene in this process have focused on DNA methylation and histone acetylation. More recently, genome-wide studies have identified histone and chromatin regulators as one of the most frequently dysregulated functional classes in a wide range of cancer types. These findings have provided numerous potential therapeutic targets including many that affect histone methylation...
September 2017: Cancer Journal
https://www.readbyqxmd.com/read/28926428/dna-methyltransferase-inhibitors-in-myeloid-cancer-clonal-eradication-or-clonal-differentiation
#13
Andreas Due Ørskov, Kirsten Grønbæk
DNA methyltransferase inhibitors, so-called hypomethylating agents (HMAs), are the only drugs approved for the treatment of higher-risk myelodysplastic syndromes and are widely used in this context. However, it is still unclear why some patients respond to HMAs, whereas others do not. Recent sequencing efforts have identified molecular disease entities that may be specifically sensitive to these drugs, and many attempts are being made to clarify how HMAs affect the malignant clone during treatment. Here, we review the most recent data on the clinical effects of HMAs in myeloid malignancies...
September 2017: Cancer Journal
https://www.readbyqxmd.com/read/28926427/dna-methylation-targeted-drugs
#14
Elodie M Da Costa, Gabrielle McInnes, Annie Beaudry, Noël J-M Raynal
Targeting DNA hypermethylation, using nucleoside analogs, is an efficient approach to reprogram cancer cell epigenome leading to reduced proliferation, increased differentiation, recognition by the immune system, and ultimately cancer cell death. DNA methyltransferase inhibitors have been approved for the treatment of myelodysplastic syndromes, chronic myelomonocytic leukemia, and acute myelogenous leukemia. To improve clinical efficacy and overcome mechanisms of drug resistance, a second generation of DNA methyltransferase inhibitors has been designed and is currently in clinical trials...
September 2017: Cancer Journal
https://www.readbyqxmd.com/read/28926163/radiomics-signature-a-potential-biomarker-for-the-prediction-of-mgmt-promoter-methylation-in-glioblastoma
#15
Yi-Bin Xi, Fan Guo, Zi-Liang Xu, Chen Li, Wei Wei, Ping Tian, Ting-Ting Liu, Lin Liu, Gang Chen, Jing Ye, Guang Cheng, Long-Biao Cui, Hong-Juan Zhang, Wei Qin, Hong Yin
BACKGROUND: In glioblastoma (GBM), promoter methylation of the DNA repair gene O-methylguanine-DNA methyltransferase (MGMT) is associated with beneficial chemotherapy. PURPOSE/HYPOTHESIS: To analyze radiomics features for utilizing the full potential of medical imaging as biomarkers of MGMT promoter methylation. STUDY TYPE: Retrospective. POPULATION/SUBJECTS: In all, 98 GBM patients with known MGMT (48 methylated and 50 unmethylated tumors)...
September 19, 2017: Journal of Magnetic Resonance Imaging: JMRI
https://www.readbyqxmd.com/read/28925878/genistein-induces-alterations-of-epigenetic-modulatory-signatures-in-human-cervical-cancer-cells
#16
Madhumitha Kedhari Sundaram, Mohammad Zeeshan Ansari, Abdullah Al Mutery, Maryam Ashraf, Reem Nasab, Sheethal Rai, Naushad Rais, Arif Hussain
Introduction Epidemiological studies indicate that diet rich in fruits and vegetables are associated with decreased cancer risk thereby indicating that dietary polyphenols can be potential chemo-preventive agents. The reversible nature of epigenetic modifications makes them a favorable target for cancer prevention. Polyphenols have been shown to reverse aberrant epigenetic patterns by targeting the regulatory enzymes, DNA methyltransferases (DNMTs) and histone deacetylases (HDACs). In vitro and in silico studies of DNMTs and HDACs were planned to examine genistein's role as a natural epigenetic modifier in human cervical cancer cells, HeLa...
September 18, 2017: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/28925385/fine-tuning-type-i-ifn-signaling-a-new-chapter-in-the-ifn-saga
#17
Hideyuki Yanai, Tadatsugu Taniguchi
Type I interferon (IFN) signaling is critical for intracellular antimicrobial programmes, affecting both innate and adaptive immune responses. The paper recently published in Cell demonstrates a new regulatory mechanism of the type I IFN signaling pathway by histone-lysine N-methyltransferase SETD2.
September 19, 2017: Cell Research
https://www.readbyqxmd.com/read/28924554/molecular-cloning-and-functional-identification-of-sterol-c24-methyltransferase-gene-from-tripterygium-wilfordii
#18
Hongyu Guan, Yujun Zhao, Ping Su, Yuru Tong, Yujia Liu, Tianyuan Hu, Yifeng Zhang, Xianan Zhang, Jia Li, Xiaoyi Wu, Luqi Huang, Wei Gao
Sterol C24-methyltransferase (SMT) plays multiple important roles in plant growth and development. SMT1, which belongs to the family of transferases and transforms cycloartenol into 24-methylene cycloartenol, is involved in the biosynthesis of 24-methyl sterols. Here, we report the cloning and characterization of a cDNA encoding a sterol C24-methyltransferase from Tripterygium wilfordii (TwSMT1). TwSMT1 (GenBank access number KU885950) is a 1530 bp cDNA with a 1041 bp open reading frame predicted to encode a 346-amino acid, 38...
September 2017: Acta Pharmaceutica Sinica. B
https://www.readbyqxmd.com/read/28924379/the-overexpression-of-carm1-promotes-human-osteosarcoma-cell-proliferation-through-the-pgsk3%C3%AE-%C3%AE-catenin-cyclind1-signaling-pathway
#19
Shijie Li, Dongdong Cheng, Bin Zhu, Qingcheng Yang
Osteosarcoma (OS) is a kind of malignant bone tumor that occurs frequently in the region surrounding the knee joint and poses a threat to the health of teenagers. Since the application of chemotherapy to treat OS, 5-year survival rate in patients has improved from 10% to 70%, but patient survival has not changed over the past four decades. Coactivator-associated arginine methyltransferase 1 (CARM1) is a member of the PRMT protein family; it acts as an oncogene in many cancers, but its function in OS is still unknown...
2017: International Journal of Biological Sciences
https://www.readbyqxmd.com/read/28924038/passive-dna-demethylation-preferentially-up-regulates-pluripotency-related-genes-and-facilitates-the-generation-of-induced-pluripotent-stem-cells
#20
Songwei He, Hao Sun, Lilong Lin, Yixin Zhang, Jinlong Chen, Lining Liang, Yuan Li, Mengdan Zhang, Xiao Yang, Xiaoshan Wang, Fuhui Wang, Feiyan Zhu, Jiekai Chen, Duanqing Pei, Hui Zheng
A high proliferation rate has been observed to facilitate somatic cell reprogramming, but the pathways that connect proliferation and reprogramming have not been reported. DNA methyltransferase 1 (DNMT1) methylates hemimethylated CpG sites produced during S phase and maintains stable inheritance of DNA methylation. Impairing this process results in passive DNA demethylation. In this study, we show that the cell proliferation rate positively correlated with the expression of Dnmt1 in G1 phase. In addition, as determined by whole genome bisulfate sequencing and high-performance liquid chromatography, global DNA methylation of mouse embryonic fibroblasts (MEFs) was significantly higher in G1 phase than in G2/M phase...
September 18, 2017: Journal of Biological Chemistry
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