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https://www.readbyqxmd.com/read/28645103/colxv-promotes-adipocyte-differentiation-via-inhibiting-dna-methylation-and-camp-pka-pathway-in-mice
#1
Guannv Liu, Meihang Li, Yatao Xu, Song Wu, Muhammad Saeed, Chao Sun
Extracellular matrix (ECM), as an essential component of adipose tissue, not only provides mechanical support for adipocyte growth, but also participates in ECM-adipocyte communication via various secreted proteins, including highly enriched collagens. Collagen XV (ColXV) is a secreted non-fibrillar collagen within ECM Basement Membrane (BM) zones and well recognized as a tumor suppressor. However, the role of ColXV in adipose tissue is still unknown. In this study, high fat diet (HFD) fed mice were used as obese model, in which we deeply investigated the interaction between ColXV and adipocyte differentiation or adipose metabolism...
June 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28644958/translating-cancer-epigenomics-into-the-clinic-focus-on-lung-cancer
#2
REVIEW
Josep Mari-Alexandre, Angel Diaz-Lagares, Maria Villalba, Oscar Juan, Ana B Crujeiras, Alfonso Calvo, Juan Sandoval
Epigenetic deregulation is increasingly being recognized as a hallmark of cancer. Recent studies have identified many new epigenetic biomarkers, some of which are being introduced into clinical practice for diagnosis, molecular classification, prognosis or prediction of response to therapies. O-6-methylguanine-DNA methyltransferase gene is the most clinically advanced epigenetic biomarker as it predicts the response to temozolomide and carmustine in gliomas. Therefore, epigenomics may represent a novel and promising tool for precision medicine, and in particular, the detection of epigenomic biomarkers in liquid biopsies will be of great interest for monitoring diseases in patients...
June 2, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28644763/methyltransferase-g9a-regulates-osteogenesis-via-twist-gene-repression
#3
N Higashihori, B Lehnertz, A Sampaio, T M Underhill, F Rossi, J M Richman
Here we investigate the role of epigenetic factors in controlling the timing of cranial neural crest cell differentiation. The gene coding for histone H3 lysine 9 methyltransferase G9A was conditionally deleted in neural crest cells with Wnt1-Cre. The majority of homozygous-null animals survived to birth but thereafter failed to thrive. Phenotypic analysis of postnatal animals revealed that the mutants displayed incomplete ossification and 20% shorter jaws as compared to their wild-type littermates. At E13...
June 1, 2017: Journal of Dental Research
https://www.readbyqxmd.com/read/28643947/effect-of-tet1-regulating-mgmt-on-chemotherapy-resistance-of-oral-squamous-cell-carcinoma-stem-cells
#4
Wei Wang, Xin Li, Fan Wang, Xiang-Yu Sun
The study was to evaluate the effect of ten-eleven translocation 1 (TET1) regulating o6-methylguanine-DNA methyltransferase (MGMT) in chemotherapy resistance of oral squamous cell carcinoma (OSCC) stem cells. OSCC stem cells were divided into the blank, negative control (NC), TET1-siRNA, TET1-siRNA + MGMT-OE and MGMT-OE groups. Methylation-specific polymerase chain reaction (MSP), qRT-PCR and western blotting were conducted to detect the methylation status of MGMT, expressions of TET1, MGMT, ABCG2 and Oct-4...
June 23, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28643785/dnmt3a-mutant-transcript-levels-persist-in-remission-and-do-not-predict-outcome-in-patients-with-acute-myeloid-leukemia
#5
V I Gaidzik, D Weber, P Paschka, A Kaumanns, S Krieger, A Corbacioglu, J Krönke, S Kapp-Schwoerer, D Krämer, H-A Horst, I Schmidt-Wolf, G Held, A Kündgen, M Ringhoffer, K Götze, T Kindler, W Fiedler, M Wattad, R F Schlenk, L Bullinger, V Teleanu, B Schlegelberger, F Thol, M Heuser, A Ganser, H Döhner, K Döhner
We investigated the prognostic impact of minimal residual disease (MRD) monitoring in acute myeloid leukemia (AML) patients harboring DNA methyltransferase 3A-R882H/-R882C mutations (DNMT3A(mut)). MRD was determined by real-time quantitative polymerase chain reaction (RQ-PCR) in 1,494 samples of 181 DNMT3A(mut) patients. At the time of diagnosis, DNMT3A(mut) transcript levels did not correlate with presenting clinical characteristics, concurrent gene mutations as well as the survival endpoints. In Cox regression analyses, bone marrow DNMT3A(mut) transcript levels (log 10 transformed continuous variable) were not associated with the rate of relapse or death...
June 23, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28643473/can-the-propensity-of-protein-crystallization-be-increased-by-using-systematic-screening-with-metals
#6
REVIEW
Raghurama P Hegde, Pavithra G Chinnaswamy, Debayan Dey, Steven C Almo, S Ramakumar, Udupi A Ramagopal
Protein crystallization is one of the major bottlenecks in protein structure elucidation with new strategies being constantly developed to improve the chances of crystallization. Generally, well-ordered epitopes possessing complementary-surface and capable of producing stable inter-protein interactions generate a regular three-dimensional arrangement of protein molecules which eventually results in a crystal lattice. Metals, when used for crystallization, with their various coordination numbers and geometries, can generate such epitopes mediating protein oligomerization and/or establish crystal contacts...
June 23, 2017: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/28643349/a-qm-mm-study-of-the-catalytic-mechanism-of-sam-methyltransferase-rlmn-from-escherichia-coli
#7
Chenxiao Zhao, Lihua Dong, Yongjun Liu
RlmN is a radical S-adenosylmethionine (SAM) enzyme that catalyzes the C2 methylation of adenosine 2503 (A2503) in 23S rRNA and adenosine 37 (A37) in several Escherichia coli transfer RNAs (tRNA). The catalytic reaction of RlmN is distinctly different from that of typical SAM-dependent methyltransferases that employs an SN 2 mechanism, but follows a ping-pong mechanism which involves the intermediate methylation of a conserved cysteine residue. Recently, the x-ray structure of a key intermediate in the RlmN reaction has been reported, allowing us to perform combined quantum mechanics and molecular mechanics (QM/MM) calculations to delineate the reaction details of RlmN at atomic level...
June 23, 2017: Proteins
https://www.readbyqxmd.com/read/28643151/multi-institutional-external-validation-of-a-novel-glioblastoma-prognostic-nomogram-incorporating-mgmt-methylation
#8
Jason K Molitoris, Yuan James Rao, Rajal A Patel, Liam T Kane, Shahed N Badiyan, Haley Gittleman, Jill S Barnholtz-Sloan, Soren M Bentzen, Tim J Kruser, Jiayi Huang, Minesh P Mehta
A recent nomogram for glioblastoma (GBM) was designed to incorporate methylguanine-DNA methyltransferase (MGMT) methylation status in trial patients receiving temozolomide. Since clinical trial patients are strictly selected, compared to the general population, we performed a multi-institutional, external, independent assessment of the nomogram. Consecutive adult patients with supratentorial GBM diagnosed between June 2007 and December 2014 who initiated TMZ-based concurrent chemoradiotherapy (CRT) and were not enrolled on RTOG 0525 or 0825 were eligible...
June 22, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28642865/spinal-muscular-atrophy-from-defective-chaperoning-of-snrnp-assembly-to-neuromuscular-dysfunction
#9
REVIEW
Maia Lanfranco, Neville Vassallo, Ruben J Cauchi
Spinal Muscular Atrophy (SMA) is a neuromuscular disorder that results from decreased levels of the survival motor neuron (SMN) protein. SMN is part of a multiprotein complex that also includes Gemins 2-8 and Unrip. The SMN-Gemins complex cooperates with the protein arginine methyltransferase 5 (PRMT5) complex, whose constituents include WD45, PRMT5 and pICln. Both complexes function as molecular chaperones, interacting with and assisting in the assembly of an Sm protein core onto small nuclear RNAs (snRNAs) to generate small nuclear ribonucleoproteins (snRNPs), which are the operating components of the spliceosome...
2017: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/28642776/regulation-involved-in-colonization-of-intercellular-spaces-of-host-plants-in-ralstonia-solanacearum
#10
REVIEW
Yasufumi Hikichi, Yuka Mori, Shiho Ishikawa, Kazusa Hayashi, Kouhei Ohnishi, Akinori Kiba, Kenji Kai
A soil-borne bacterium Ralstonia solanacearum invading plant roots first colonizes the intercellular spaces of the root, and eventually enters xylem vessels, where it replicates at high levels leading to wilting symptoms. After invasion into intercellular spaces, R. solanacearum strain OE1-1 attaches to host cells and expression of the hrp genes encoding components of the type III secretion system (T3SS). OE1-1 then constructs T3SS and secrets effectors into host cells, inducing expression of the host gene encoding phosphatidic acid phosphatase...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28640505/associations-between-arsenic-3-oxidation-state-methyltransferase-as3mt-and-n-6-adenine-specific-dna-methyltransferase-1-n6amt1-polymorphisms-arsenic-metabolism-and-cancer-risk-in-a-chilean-population
#11
Rosemarie de la Rosa, Craig Steinmaus, Nicholas K Akers, Lucia Conde, Catterina Ferreccio, David Kalman, Kevin R Zhang, Christine F Skibola, Allan H Smith, Luoping Zhang, Martyn T Smith
Inter-individual differences in arsenic metabolism have been linked to arsenic-related disease risks. Arsenic (+3) methyltransferase (AS3MT) is the primary enzyme involved in arsenic metabolism, and we previously demonstrated in vitro that N-6 adenine-specific DNA methyltransferase 1 (N6AMT1) also methylates the toxic inorganic arsenic (iAs) metabolite, monomethylarsonous acid (MMA), to the less toxic dimethylarsonic acid (DMA). Here, we evaluated whether AS3MT and N6AMT1 gene polymorphisms alter arsenic methylation and impact iAs-related cancer risks...
June 22, 2017: Environmental and Molecular Mutagenesis
https://www.readbyqxmd.com/read/28640434/catechol-o-methyltransferase-genotype-and-gait-speed-changes-over-10-years-in-older-adults
#12
Andrea L Metti, Caterina Rosano, Robert Boudreau, Robyn Massa, Kristine Yaffe, Suzanne Satterfield, Tamara Harris, Andrea L Rosso
OBJECTIVES: To determine the association between catechol-O-methyltransferase (COMT) genotype and 6-m walk time and to determine whether these associations are quadratic in nature, similar to previously reported U-shaped associations between dopamine and gait and cognition. DESIGN: Prospective cohort study. SETTING: Health, Aging and Body Composition Study. PARTICIPANTS: Black (n = 850) and white (n = 1,352) men and women with a mean age of 73...
June 22, 2017: Journal of the American Geriatrics Society
https://www.readbyqxmd.com/read/28639934/first-description-of-methyltransferases-in-extensively-drug-resistant-klebsiella-pneumoniae-isolates-from-saudi-arabia
#13
Baha Abdalhamid, Nasreldin Elhadi, Samar Albunayan, Khaldoon Alsamman, Reem Aljindan
PURPOSE: The resistance determinants for carbapenems, fluoroquinolones and aminoglycosides were characterized in 16 extensively drug-resistant Klebsiella pneumoniae (XDRKPN) strains collected from Saudi hospitals during 2014. METHODOLOGY: PCR and sequencing were used to detect: blaKPC, blaNDM, blaVIM, blaIMP-1,blaOXA-48, blaCTX-M, blaTEM, blaSHV and ampC for β-lactam resistance; qnrA, qnrB, qnrS, aac(6')-Ib-cr, qepA and mutations of gyrA and parC for fluoroquinolone resistance; and aacA4, aacC2, aadA1, aphA6, armA and rmtB for aminoglycoside resistance...
June 22, 2017: Journal of Medical Microbiology
https://www.readbyqxmd.com/read/28639750/protein-lysine-methyltransferase-smyd3-is-involved-in-tumorigenesis-through-regulation-of-her2-homodimerization
#14
Yuichiro Yoshioka, Takehiro Suzuki, Yo Matsuo, Giichiro Tsurita, Toshiaki Watanabe, Naoshi Dohmae, Yusuke Nakamura, Ryuji Hamamoto
HER2 is a receptor tyrosine kinase, which is amplified and overexpressed in a subset of human cancers including breast and gastric cancers, and is indicated in its involvement in progression of cancer. Although its specific ligand(s) has not been detected, HER2 homodimerization, which is critical for its activation, is considered to be dependent on its expression levels. Here, we demonstrate a significant role of HER2 methylation by protein lysine methyltransferase SMYD3 in HER2 homodimerization. We found that SMYD3 trimethylates HER2 protein at lysine 175...
June 22, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28639476/effects-of-folic-acid-on-dnmt1-gap43-and-vegfr1-in-intrauterine-growth-restriction-filial-rats
#15
Ying-Xue Ding, Hong Cui
OBJECTIVE: To investigate the effect of a folic acid intervention on the outcome of intrauterine growth restriction (IUGR) filial rats and changes in DNA methyltransferase 1 (DNMT1), growth-associated protein 43 (GAP43), and vascular endothelial growth factor receptor 1 (VEGFR1). METHODS: The IUGR animal model was established using a starvation method in pregnant rats. The animals were randomly divided into 4 groups: normal controls, IUGR rats, IUGR rats given folic acid, and IUGR rats given normal saline...
January 1, 2017: Reproductive Sciences
https://www.readbyqxmd.com/read/28639412/the-role-of-microrna-5196-in-the-pathogenesis-of-systemic-sclerosis
#16
Marzena Ciechomska, Patryk Zarecki, Michal Merdas, Jerzy Swierkot, Ewa Morgiel, Piotr Wiland, Wlodzimierz Maslinski, Katarzyna Bogunia-Kubik
BACKGROUND: Systemic sclerosis (SSc) is a chronic autoimmune disease characterised by tissue fibrosis and immune abnormalities. Recent evidence suggests that activated circulating monocytes from SSc patients play an important role in early stages of SSc pathogenesis due to enhanced expression of tissue inhibitor of metalloproteinases 1 (TIMP-1), IL-8 and reactive oxygen species (ROS) induction. However, the exact factors that contribute to chronic inflammation and subsequently fibrosis progression are still unknown...
June 21, 2017: European Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28638238/a-computational-methodology-to-overcome-the-challenges-associated-with-the-search-for-specific-enzyme-targets-to-develop-drugs-against-leishmania-major
#17
Larissa Catharina, Carlyle Ribeiro Lima, Alexander Franca, Ana Carolina Ramos Guimarães, Marcelo Alves-Ferreira, Pierre Tuffery, Philippe Derreumaux, Nicolas Carels
We present an approach for detecting enzymes that are specific of Leishmania major compared with Homo sapiens and provide targets that may assist research in drug development. This approach is based on traditional techniques of sequence homology comparison by similarity search and Markov modeling; it integrates the characterization of enzymatic functionality, secondary and tertiary protein structures, protein domain architecture, and metabolic environment. From 67 enzymes represented by 42 enzymatic activities classified by AnEnPi (Analogous Enzymes Pipeline) as specific for L major compared with H sapiens, only 40 (23 Enzyme Commission [EC] numbers) could actually be considered as strictly specific of L major and 27 enzymes (19 EC numbers) were disregarded for having ambiguous homologies or analogies with H sapiens...
2017: Bioinformatics and Biology Insights
https://www.readbyqxmd.com/read/28637770/analgesia-and-opioids-a-pharmacogenetics-shortlist-for-implementation-in-clinical-practice
#18
REVIEW
Maja Matic, Saskia N de Wildt, Dick Tibboel, Ron H N van Schaik
BACKGROUND: The use of opioids to alleviate pain is complicated by the risk of severe adverse events and the large variability in dose requirements. Pharmacogenetics (PGx) could possibly be used to tailor pain medication based on an individual's genetic background. Many potential genetic markers have been described, and the importance of genetic predisposition in opioid efficacy and toxicity has been demonstrated in knockout mouse models and human twin studies. Such predictors are especially of value for neonates and young children, in whom the assessment of efficacy or side effects is complicated by the inability of the patient to communicate this properly...
June 21, 2017: Clinical Chemistry
https://www.readbyqxmd.com/read/28637748/impaired-spliceosomal-usnrnp-assembly-leads-to-sm-mrna-down-regulation-and-sm-protein-degradation
#19
Archana Bairavasundaram Prusty, Rajyalakshmi Meduri, Bhupesh Kumar Prusty, Jens Vanselow, Andreas Schlosser, Utz Fischer
Specialized assembly factors facilitate the formation of many macromolecular complexes in vivo. The formation of Sm core structures of spliceosomal U-rich small nuclear ribonucleoprotein particles (UsnRNPs) requires assembly factors united in protein arginine methyltransferase 5 (PRMT5) and survival motor neuron (SMN) complexes. We demonstrate that perturbations of this assembly machinery trigger complex cellular responses that prevent aggregation of unassembled Sm proteins. Inactivation of the SMN complex results in the initial tailback of Sm proteins on the PRMT5 complex, followed by down-regulation of their encoding mRNAs...
June 21, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28637692/m-6-a-mrna-modifications-are-deposited-in-nascent-pre-mrna-and-are-not-required-for-splicing-but-do-specify-cytoplasmic-turnover
#20
Shengdong Ke, Amy Pandya-Jones, Yuhki Saito, John J Fak, Cathrine Broberg Vågbø, Shay Geula, Jacob H Hanna, Douglas L Black, James E Darnell, Robert B Darnell
Understanding the biologic role of N(6)-methyladenosine (m(6)A) RNA modifications in mRNA requires an understanding of when and where in the life of a pre-mRNA transcript the modifications are made. We found that HeLa cell chromatin-associated nascent pre-mRNA (CA-RNA) contains many unspliced introns and m(6)A in exons but very rarely in introns. The m(6)A methylation is essentially completed upon the release of mRNA into the nucleoplasm. Furthermore, the content and location of each m(6)A modification in steady-state cytoplasmic mRNA are largely indistinguishable from those in the newly synthesized CA-RNA or nucleoplasmic mRNA...
May 15, 2017: Genes & Development
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