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Pesquisa : D13.695.250 [Categoria DeCS]
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[PMID]:28931024
[Au] Autor:Elmariah S
[Ad] Endereço:Cardiology Division, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.
[Ti] Título:Formal comment to Toyota et al.: Short versus prolonged dual antiplatelet therapy (DAPT) duration after coronary stent implantation: A comparison between the DAPT study and 9 other trials evaluating DAPT duration.
[So] Source:PLoS One;12(9):e0184513, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Mh] Termos MeSH primário: Stents Farmacológicos
Inibidores da Agregação de Plaquetas
[Mh] Termos MeSH secundário: Fosfatos de Dinucleosídeos
Seres Humanos
[Pt] Tipo de publicação:JOURNAL ARTICLE; COMMENT
[Nm] Nome de substância:
0 (Dinucleoside Phosphates); 0 (Platelet Aggregation Inhibitors); 19192-40-6 (2'-deoxythymidylyl-(3'-5')-2'-deoxyadenosine)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171106
[Lr] Data última revisão:
171106
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170921
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0184513


  2 / 2479 MEDLINE  
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[PMID]:28767234
[Au] Autor:Onuk E; Badger J; Wang YJ; Bardhan J; Chishti Y; Akcakaya M; Brooks DH; Erdogmus D; Minh DDL; Makowski L
[Ad] Endereço:Radiation Oncology Department, University of California , Los Angeles, California 90095, United States.
[Ti] Título:Effects of Catalytic Action and Ligand Binding on Conformational Ensembles of Adenylate Kinase.
[So] Source:Biochemistry;56(34):4559-4567, 2017 Aug 29.
[Is] ISSN:1520-4995
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Crystal structures of adenylate kinase (AdK) from Escherichia coli capture two states: an "open" conformation (apo) obtained in the absence of ligands and a "closed" conformation in which ligands are bound. Other AdK crystal structures suggest intermediate conformations that may lie on the transition pathway between these two states. To characterize the transition from open to closed states in solution, X-ray solution scattering data were collected from AdK in the apo form and with progressively increasing concentrations of five different ligands. Scattering data from apo AdK are consistent with scattering predicted from the crystal structure of AdK in the open conformation. In contrast, data from AdK samples saturated with Ap5A do not agree with that calculated from AdK in the closed conformation. Using cluster analysis of available structures, we selected representative structures in five conformational states: open, partially open, intermediate, partially closed, and closed. We used these structures to estimate the relative abundances of these states for each experimental condition. X-ray solution scattering data obtained from AdK with AMP are dominated by scattering from AdK in the open conformation. For AdK in the presence of high concentrations of ATP and ADP, the conformational ensemble shifts to a mixture of partially open and closed states. Even when AdK is saturated with Ap5A, a significant proportion of AdK remains in a partially open conformation. These results are consistent with an induced-fit model in which the transition of AdK from an open state to a closed state is initiated by ATP binding.
[Mh] Termos MeSH primário: Difosfato de Adenosina/química
Trifosfato de Adenosina/química
Adenilato Quinase/química
Fosfatos de Dinucleosídeos/química
Proteínas de Escherichia coli/química
Escherichia coli/enzimologia
[Mh] Termos MeSH secundário: Adenilato Quinase/genética
Domínio Catalítico
Cristalografia por Raios X
Escherichia coli/genética
Proteínas de Escherichia coli/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Dinucleoside Phosphates); 0 (Escherichia coli Proteins); 50304-44-4 (P(1),P(5)-di(adenosine-5'-)pentaphosphate); 61D2G4IYVH (Adenosine Diphosphate); 8L70Q75FXE (Adenosine Triphosphate); EC 2.7.4.3 (Adenylate Kinase)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170831
[Lr] Data última revisão:
170831
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170803
[St] Status:MEDLINE
[do] DOI:10.1021/acs.biochem.7b00351


  3 / 2479 MEDLINE  
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[PMID]:28666355
[Au] Autor:Rydzik AM; Warminski M; Sikorski PJ; Baranowski MR; Walczak S; Kowalska J; Zuberek J; Lukaszewicz M; Nowak E; W Claridge TD; Darzynkiewicz E; Nowotny M; Jemielity J
[Ad] Endereço:Division of Biophysics, Institute of Experimental Physics, Faculty of Physics, University of Warsaw, Zwirki i Wigury 93, 02-089 Warsaw, Poland.
[Ti] Título:mRNA cap analogues substituted in the tetraphosphate chain with CX2: identification of O-to-CCl2 as the first bridging modification that confers resistance to decapping without impairing translation.
[So] Source:Nucleic Acids Res;45(15):8661-8675, 2017 Sep 06.
[Is] ISSN:1362-4962
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Analogues of the mRNA 5'-cap are useful tools for studying mRNA translation and degradation, with emerging potential applications in novel therapeutic interventions including gene therapy. We report the synthesis of novel mono- and dinucleotide cap analogues containing dihalogenmethylenebisphosphonate moiety (i.e. one of the bridging O atom substituted with CCl2 or CF2) and their properties in the context of cellular translational and decapping machineries, compared to phosphate-unmodified and previously reported CH2-substituted caps. The analogues were bound tightly to eukaryotic translation initiation factor 4E (eIF4E), with CCl2-substituted analogues having the highest affinity. When incorporated into mRNA, the CCl2-substituted dinucleotide most efficiently promoted cap-dependent translation. Moreover, the CCl2-analogues were potent inhibitors of translation in rabbit reticulocyte lysate. The crystal structure of eIF4E in complex with the CCl2-analogue revealed a significantly different ligand conformation compared to that of the unmodified cap analogue, which likely contributes to the improved binding. Both CCl2- and CF2- analogues showed lower susceptibility to hydrolysis by the decapping scavenger enzyme (DcpS) and, when incorporated into RNA, conferred stability against major cellular decapping enzyme (Dcp2) to transcripts. Furthermore, the use of difluoromethylene cap analogues was exemplified by the development of 19F NMR assays for DcpS activity and eIF4E binding.
[Mh] Termos MeSH primário: Endorribonucleases/metabolismo
Biossíntese de Proteínas/efeitos dos fármacos
Análogos de Capuz de RNA/farmacologia
Processamento Pós-Transcricional do RNA/efeitos dos fármacos
RNA Mensageiro/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Sítios de Ligação/efeitos dos fármacos
Cristalografia por Raios X
Fosfatos de Dinucleosídeos/química
Fosfatos de Dinucleosídeos/metabolismo
Fator de Iniciação 4E em Eucariotos/metabolismo
Células HeLa
Seres Humanos
Camundongos
Modelos Moleculares
Análogos de Capuz de RNA/química
Análogos de Capuz de RNA/metabolismo
Capuzes de RNA/química
Capuzes de RNA/efeitos dos fármacos
Capuzes de RNA/metabolismo
RNA Mensageiro/química
RNA Mensageiro/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Dinucleoside Phosphates); 0 (Eukaryotic Initiation Factor-4E); 0 (RNA Cap Analogs); 0 (RNA Caps); 0 (RNA, Messenger); 0 (mRNA decapping enzymes); EC 3.1.- (Endoribonucleases)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171107
[Lr] Data última revisão:
171107
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170702
[St] Status:MEDLINE
[do] DOI:10.1093/nar/gkx569


  4 / 2479 MEDLINE  
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[PMID]:28630043
[Au] Autor:Johnson CW; Reid D; Parker JA; Salter S; Knihtila R; Kuzmic P; Mattos C
[Ad] Endereço:From the Department of Chemistry and Chemical Biology, Northeastern University, Boston, Massachusetts 02115 and.
[Ti] Título:The small GTPases K-Ras, N-Ras, and H-Ras have distinct biochemical properties determined by allosteric effects.
[So] Source:J Biol Chem;292(31):12981-12993, 2017 Aug 04.
[Is] ISSN:1083-351X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:H-Ras, K-Ras, and N-Ras are small GTPases that are important in the control of cell proliferation, differentiation, and survival, and their mutants occur frequently in human cancers. The G-domain, which catalyzes GTP hydrolysis and mediates downstream signaling, is 95% conserved between the Ras isoforms. Because of their very high sequence identity, biochemical studies done on H-Ras have been considered representative of all three Ras proteins. We show here that this is not a valid assumption. Using enzyme kinetic assays under identical conditions, we observed clear differences between the three isoforms in intrinsic catalysis of GTP by Ras in the absence and presence of the Ras-binding domain (RBD) of the c-Raf kinase protein (Raf-RBD). Given their identical active sites, isoform G-domain differences must be allosteric in origin, due to remote isoform-specific residues that affect conformational states. We present the crystal structure of N-Ras bound to a GTP analogue and interpret the kinetic data in terms of structural features specific for H-, K-, and N-Ras.
[Mh] Termos MeSH primário: GTP Fosfo-Hidrolases/metabolismo
Guanosina Trifosfato/metabolismo
Proteínas de Membrana/metabolismo
Modelos Moleculares
Proteínas Proto-Oncogênicas c-raf/metabolismo
Proteínas Proto-Oncogênicas p21(ras)/metabolismo
[Mh] Termos MeSH secundário: Regulação Alostérica
Sítio Alostérico
Substituição de Aminoácidos
Biocatálise
Domínio Catalítico
Cristalografia por Raios X
Fosfatos de Dinucleosídeos/química
Fosfatos de Dinucleosídeos/metabolismo
Estabilidade Enzimática
GTP Fosfo-Hidrolases/química
GTP Fosfo-Hidrolases/genética
Guanosina Trifosfato/análogos & derivados
Guanosina Trifosfato/química
Seres Humanos
Isoenzimas/química
Isoenzimas/genética
Isoenzimas/metabolismo
Ligantes
Proteínas de Membrana/química
Proteínas de Membrana/genética
Fragmentos de Peptídeos/química
Fragmentos de Peptídeos/genética
Fragmentos de Peptídeos/metabolismo
Mutação Puntual
Conformação Proteica
Domínios e Motivos de Interação entre Proteínas
Proteínas Proto-Oncogênicas c-raf/química
Proteínas Proto-Oncogênicas c-raf/genética
Proteínas Proto-Oncogênicas p21(ras)/química
Proteínas Proto-Oncogênicas p21(ras)/genética
Proteínas Recombinantes/química
Proteínas Recombinantes/metabolismo
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Dinucleoside Phosphates); 0 (Isoenzymes); 0 (KRAS protein, human); 0 (Ligands); 0 (Membrane Proteins); 0 (Peptide Fragments); 0 (Recombinant Proteins); 78101-73-2 (diguanosine pentaphosphate); 86-01-1 (Guanosine Triphosphate); EC 2.7.11.1 (Proto-Oncogene Proteins c-raf); EC 3.6.1.- (GTP Phosphohydrolases); EC 3.6.1.- (NRAS protein, human); EC 3.6.5.2 (HRAS protein, human); EC 3.6.5.2 (Proto-Oncogene Proteins p21(ras))
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170825
[Lr] Data última revisão:
170825
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170621
[St] Status:MEDLINE
[do] DOI:10.1074/jbc.M117.778886


  5 / 2479 MEDLINE  
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[PMID]:28557349
[Au] Autor:Kiuru E; Malmikare S; Ora M
[Ad] Endereço:Department of Chemistry, University of Turku, FI-20014, Turku.
[Ti] Título:Synthesis and Deprotection of Biodegradably and Thermally Protected Dinucleoside-2',5'-Monophosphate Prodrug Model of 2-5A.
[So] Source:Chem Biodivers;14(9), 2017 Sep.
[Is] ISSN:1612-1880
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:Protected dinucleoside-2',5'-monophosphate has been prepared to develop a prodrug strategy for 2-5A. The removal of enzymatically and thermally labile 4-(acetylthio)-2-(ethoxycarbonyl)-3-oxo-2-methylbutyl phosphate protecting group and enzymatically labile 3'-O-pivaloyloxymethyl group was followed at pH 7.5 and 37 °C by HPLC from the fully protected dimeric adenosine-2',5'-monophosphate 1 used as a model compound for 2-5A. The desired unprotected 2',3'-O-isopropylideneadenosine-2',5'-monophosphate (9) was observed to accumulate as a major product. Neither the competitive isomerization of 2',5'- to a 3',5'-linkage nor the P-O5' bond cleavage was detected. The phosphate protecting group was removed faster than the 3'-O-protection and, hence, the attack of the neighbouring 3'-OH on phosphotriester moiety did not take place.
[Mh] Termos MeSH primário: Monofosfato de Adenosina/síntese química
Fosfatos de Dinucleosídeos/síntese química
Pró-Fármacos/síntese química
[Mh] Termos MeSH secundário: Monofosfato de Adenosina/química
Cromatografia Líquida de Alta Pressão
Dimerização
Fosfatos de Dinucleosídeos/química
Pró-Fármacos/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Dinucleoside Phosphates); 0 (Prodrugs); 415SHH325A (Adenosine Monophosphate)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171006
[Lr] Data última revisão:
171006
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170531
[St] Status:MEDLINE
[do] DOI:10.1002/cbdv.201700220


  6 / 2479 MEDLINE  
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[PMID]:28516732
[Au] Autor:Despotovic D; Brandis A; Savidor A; Levin Y; Fumagalli L; Tawfik DS
[Ad] Endereço:Department of Biomolecular Sciences, Weizmann Institute of Science, Rehovot, Israel.
[Ti] Título:Diadenosine tetraphosphate (Ap4A) - an E. coli alarmone or a damage metabolite?
[So] Source:FEBS J;284(14):2194-2215, 2017 Jul.
[Is] ISSN:1742-4658
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Under stress, metabolism is changing: specific up- or down-regulation of proteins and metabolites occurs as well as side effects. Distinguishing specific stress-signaling metabolites (alarmones) from side products (damage metabolites) is not trivial. One example is diadenosine tetraphosphate (Ap4A) - a side product of aminoacyl-tRNA synthetases found in all domains of life. The earliest observations suggested that Ap4A serves as an alarmone for heat stress in Escherichia coli. However, despite 50 years of research, the signaling mechanisms associated with Ap4A remain unknown. We defined a set of criteria for distinguishing alarmones from damage metabolites to systematically classify Ap4A. In a nutshell, no indications for a signaling cascade that is triggered by Ap4A were found; rather, we found that Ap4A is efficiently removed in a constitutive, nonregulated manner. Several fold perturbations in Ap4A concentrations have no effect, yet accumulation at very high levels is toxic due to disturbance of zinc homeostasis, and also because Ap4A's structural overlap with ATP can result in spurious binding and inactivation of ATP-binding proteins. Overall, Ap4A met all criteria for a damage metabolite. While we do not exclude any role in signaling, our results indicate that the damage metabolite option should be considered as the null hypothesis when examining Ap4A and other metabolites whose levels change upon stress.
[Mh] Termos MeSH primário: Fosfatos de Dinucleosídeos/metabolismo
Escherichia coli/metabolismo
Estresse Fisiológico
[Mh] Termos MeSH secundário: Hidrolases Anidrido Ácido/genética
Hidrolases Anidrido Ácido/metabolismo
Escherichia coli/genética
Escherichia coli/crescimento & desenvolvimento
Proteínas de Escherichia coli/genética
Proteínas de Escherichia coli/metabolismo
Regulação Bacteriana da Expressão Gênica
Homeostase
Lisina-tRNA Ligase/genética
Lisina-tRNA Ligase/metabolismo
Transdução de Sinais
Zinco/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Dinucleoside Phosphates); 0 (Escherichia coli Proteins); 5542-28-9 (diadenosine tetraphosphate); EC 3.6.- (Acid Anhydride Hydrolases); EC 3.6.1.- (ApaH protein, E coli); EC 6.1.1.6 (Lysine-tRNA Ligase); J41CSQ7QDS (Zinc)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170926
[Lr] Data última revisão:
170926
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170519
[St] Status:MEDLINE
[do] DOI:10.1111/febs.14113


  7 / 2479 MEDLINE  
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[PMID]:28511132
[Au] Autor:Gándara C; de Lucena DKC; Torres R; Serrano E; Altenburger S; Graumann PL; Alonso JC
[Ad] Endereço:Departamento de Biotecnología Microbiana, Centro Nacional de Biotecnología, CNB-CSIC, Madrid, Spain.
[Ti] Título:Activity and in vivo dynamics of Bacillus subtilis DisA are affected by RadA/Sms and by Holliday junction-processing proteins.
[So] Source:DNA Repair (Amst);55:17-30, 2017 Jul.
[Is] ISSN:1568-7856
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Bacillus subtilis c-di-AMP synthase DisA and RecA-related RadA/Sms are involved in the repair of DNA damage in exponentially growing cells. We provide genetic evidence that DisA or RadA/Sms is epistatic to the branch migration translocase (BMT) RecG and the Holliday junction (HJ) resolvase RecU in response to DNA damage. We provide genetic evidence damage. Functional DisA-YFP formed dynamic foci in exponentially growing cells, which moved through the nucleoids at a speed compatible with a DNA-scanning mode. DisA formed more static structures in the absence of RecU or RecG than in wild type cells, while dynamic foci were still observed in cells lacking the BMT RuvAB. Purified DisA synthesizes c-di-AMP, but interaction with RadA/Sms or with HJ DNA decreases DisA-mediated c-di-AMP synthesis. RadA/Sms-YFP also formed dynamic foci in growing cells, but the foci moved throughout the cells rather than just on the nucleoids, and co-localized rarely with DisA-YFP foci, suggesting that RadA/Sms and DisA interact only transiently in unperturbed conditions. Our data suggest a model in which DisA moving along dsDNA indicates absence of DNA damage/replication stress via normal c-di-AMP levels, while interaction with HJ DNA/halted forks leads to reduced c-di-AMP levels and an ensuing block in cell proliferation. RadA/Sms may be involved in modulating DisA activities.
[Mh] Termos MeSH primário: Bacillus subtilis/enzimologia
Proteínas de Bactérias/metabolismo
DNA Cruciforme/metabolismo
Proteínas de Ligação a DNA/metabolismo
Nucleotidiltransferases/metabolismo
Reparo de DNA por Recombinação
[Mh] Termos MeSH secundário: Bacillus subtilis/genética
Dano ao DNA
Replicação do DNA
DNA Bacteriano/metabolismo
Fosfatos de Dinucleosídeos/biossíntese
Resolvases de Junção Holliday
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Bacterial Proteins); 0 (DNA, Bacterial); 0 (DNA, Cruciform); 0 (DNA-Binding Proteins); 0 (Dinucleoside Phosphates); 0 (RadA protein, bacteria); 0 (cyclic diadenosine phosphate); EC 2.7.7.- (Nucleotidyltransferases); EC 3.1.21.- (Holliday Junction Resolvases)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170810
[Lr] Data última revisão:
170810
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170517
[St] Status:MEDLINE


  8 / 2479 MEDLINE  
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[PMID]:28420751
[Au] Autor:Gundlach J; Herzberg C; Kaever V; Gunka K; Hoffmann T; Weiß M; Gibhardt J; Thürmer A; Hertel D; Daniel R; Bremer E; Commichau FM; Stülke J
[Ad] Endereço:Department of General Microbiology, Georg-August-University Göttingen, 37077 Göttingen, Germany.
[Ti] Título:Control of potassium homeostasis is an essential function of the second messenger cyclic di-AMP in .
[So] Source:Sci Signal;10(475), 2017 Apr 18.
[Is] ISSN:1937-9145
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The second messenger cyclic di-adenosine monophosphate (c-di-AMP) is essential in the Gram-positive model organism and in related pathogenic bacteria. It controls the activity of the conserved riboswitch and of several proteins involved in potassium (K ) uptake. We found that the YdaO protein was conserved among several different bacteria and provide evidence that YdaO functions as a K transporter. Thus, we renamed the gene and protein KimA (K importer A). Reporter activity assays indicated that expression beyond the c-di-AMP-responsive riboswitch of the upstream regulatory region occurred only in bacteria grown in medium containing low K concentrations. Furthermore, mass spectrometry analysis indicated that c-di-AMP accumulated in bacteria grown in the presence of high K concentrations but not in low concentrations. A bacterial strain lacking all genes encoding c-di-AMP-synthesizing enzymes was viable when grown in medium containing low K concentrations, but not at higher K concentrations unless it acquired suppressor mutations in the gene encoding the cation exporter NhaK. Thus, our results indicated that the control of potassium homeostasis is an essential function of c-di-AMP.
[Mh] Termos MeSH primário: Bacillus subtilis/metabolismo
Fosfatos de Dinucleosídeos/metabolismo
Homeostase/fisiologia
Potássio/metabolismo
Sistemas do Segundo Mensageiro/fisiologia
[Mh] Termos MeSH secundário: Bacillus subtilis/genética
Proteínas de Bactérias/genética
Proteínas de Bactérias/metabolismo
Fosfatos de Dinucleosídeos/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Bacterial Proteins); 0 (Dinucleoside Phosphates); 0 (cyclic diadenosine phosphate); RWP5GA015D (Potassium)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170727
[Lr] Data última revisão:
170727
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170420
[St] Status:MEDLINE


  9 / 2479 MEDLINE  
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[PMID]:28412323
[Au] Autor:Tsuboi K; Nagatomo T; Gohno T; Higuchi T; Sasaki S; Fujiki N; Kurosumi M; Takei H; Yamaguchi Y; Niwa T; Hayashi SI
[Ad] Endereço:Department of Molecular and Functional Dynamics, Graduate School of Medicine, Tohoku University, Aoba-ku, Sendai, 980-8575, Japan.
[Ti] Título:Single CpG site methylation controls estrogen receptor gene transcription and correlates with hormone therapy resistance.
[So] Source:J Steroid Biochem Mol Biol;171:209-217, 2017 Jul.
[Is] ISSN:1879-1220
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Hormone therapy is the most effective treatment for patients with estrogen receptor α-positive breast cancers. However, although resistance occurs during treatment in some cases and often reflects changed estrogen receptor α status, the relationship between changes in estrogen receptor α expression and resistance to therapy are poorly understood. In this study, we identified a mechanism for altered estrogen receptor α expression during disease progression and acquired hormone therapy resistance in aromatase inhibitor-resistant breast cancer cell lines. Subsequently, we investigated promoter switching and DNA methylation status of the estrogen receptor α promoter, and found marked changes of methylation at a single CpG site (CpG4) in resistant cells. In addition, luciferase reporter assays showed reduced transcriptional activity from this methylated CpG site. This CpG region was also completely conserved among species, suggesting that it acts as a methylation-sensitive Ets-2 transcription factor binding site, as confirmed using chromatin immunoprecipitation assays. In estrogen receptor α-positive tumors, CpG4 methylation levels were inversely correlated with estrogen receptor α expression status, suggesting that single CpG site plays an important role in the regulation of estrogen receptor α transcription.
[Mh] Termos MeSH primário: Neoplasias da Mama/metabolismo
Metilação de DNA
Fosfatos de Dinucleosídeos/metabolismo
Receptor alfa de Estrogênio/metabolismo
Regiões Promotoras Genéticas
Proteína Proto-Oncogênica c-ets-2/metabolismo
Transcrição Genética
[Mh] Termos MeSH secundário: Antineoplásicos Hormonais/farmacologia
Inibidores da Aromatase/farmacologia
Sequência de Bases
Neoplasias da Mama/tratamento farmacológico
Sequência Conservada
Metilação de DNA/efeitos dos fármacos
DNA Recombinante/metabolismo
Resistência a Medicamentos Antineoplásicos
Receptor alfa de Estrogênio/química
Receptor alfa de Estrogênio/genética
Feminino
Genes Reporter/efeitos dos fármacos
Seres Humanos
Células MCF-7
Meia-Idade
Mutação
Proteínas de Neoplasias/química
Proteínas de Neoplasias/genética
Proteínas de Neoplasias/metabolismo
Regiões Promotoras Genéticas/efeitos dos fármacos
Proteína Proto-Oncogênica c-ets-2/genética
Proteínas Recombinantes/metabolismo
Elementos de Resposta/efeitos dos fármacos
Transcrição Genética/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents, Hormonal); 0 (Aromatase Inhibitors); 0 (DNA, Recombinant); 0 (Dinucleoside Phosphates); 0 (ETS2 protein, human); 0 (Estrogen Receptor alpha); 0 (Neoplasm Proteins); 0 (Proto-Oncogene Protein c-ets-2); 0 (Recombinant Proteins); 0 (estrogen receptor alpha, human); 2382-65-2 (cytidylyl-3'-5'-guanosine)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170718
[Lr] Data última revisão:
170718
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170417
[St] Status:MEDLINE


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[PMID]:28347177
[Au] Autor:Sadiq FA; Flint S; Li Y; Liu T; Lei Y; Sakandar HA; He G
[Ad] Endereço:a College of Biosystems Engineering and Food Science , Zhejiang University , Hangzhou , PR China.
[Ti] Título:New mechanistic insights into the motile-to-sessile switch in various bacteria with particular emphasis on Bacillus subtilis and Pseudomonas aeruginosa: a review.
[So] Source:Biofouling;33(4):306-326, 2017 Apr.
[Is] ISSN:1029-2454
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:A biofilm is a complex assemblage of microbial communities adhered to a biotic or an abiotic surface which is embedded within a self-produced matrix of extracellular polymeric substances. Many transcriptional regulators play a role in triggering a motile-sessile switch and in consequently producing the biofilm matrix. This review is aimed at highlighting the role of two nucleotide signaling molecules (c-di-GMP and c-di-AMP), toxin antitoxin modules and a novel transcriptional regulator BolA in biofilm formation in various bacteria. In addition, it highlights the common themes that have appeared in recent research regarding the key regulatory components and signal transduction pathways that help Bacillus subtilis and Pseudomonas aeruginosa to acquire the biofilm mode of life.
[Mh] Termos MeSH primário: Bacillus subtilis/fisiologia
Biofilmes/crescimento & desenvolvimento
GMP Cíclico/análogos & derivados
Fosfatos de Dinucleosídeos/metabolismo
Pseudomonas aeruginosa/fisiologia
Transdução de Sinais
[Mh] Termos MeSH secundário: Bacillus subtilis/genética
GMP Cíclico/genética
GMP Cíclico/metabolismo
Fosfatos de Dinucleosídeos/genética
Matriz Extracelular/metabolismo
Regulação Bacteriana da Expressão Gênica
Pseudomonas aeruginosa/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Dinucleoside Phosphates); 0 (cyclic diadenosine phosphate); 61093-23-0 (bis(3',5')-cyclic diguanylic acid); H2D2X058MU (Cyclic GMP)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170906
[Lr] Data última revisão:
170906
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170329
[St] Status:MEDLINE
[do] DOI:10.1080/08927014.2017.1304541



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