Base de dados : MEDLINE
Pesquisa : D12.776.624.664.520.750.875 [Categoria DeCS]
Referências encontradas : 230 [refinar]
Mostrando: 1 .. 10   no formato [Detalhado]

página 1 de 23 ir para página                         

  1 / 230 MEDLINE  
              next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28573218
[Au] Autor:Sangkaruk R; Rungrojsakul M; Tima S; Anuchapreeda S
[Ad] Endereço:Division of Clinical Microscopy, Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200 Thailand.
[Ti] Título:EFFECT OF THAI SARAPHI FLOWER EXTRACTS ON WT1 AND BCR/ABL PROTEIN EXPRESSION IN LEUKEMIC CELL LINES.
[So] Source:Afr J Tradit Complement Altern Med;14(2):16-24, 2017.
[Is] ISSN:2505-0044
[Cp] País de publicação:Nigeria
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Saraphi is a Thai traditional herb. In this study, the cytotoxic effects of crude ethanolic and fractional extracts including hexane, ethyl acetate, and methanol fractions from flowers were investigated in order to determine their effect on WT1 expression in Molt4 and K562 cells and Bcr/Abl expression in K562 cells. MATERIALS AND METHODS: The flowers of were extracted using ethanol. The ethanol flower extract was further fractionated with hexane, ethyl acetate, and methanol. Cytotoxic effects were measured by the MTT assay. Bcr/Abl and WT1 protein levels after treatments were determined by Western blotting. The total cell number was determined the typan blue exclusion method. RESULTS: The hexane fraction showed the strongest cytotoxic activity on Molt4 and K562 cells, with IC values of 2.6 and 77.6 µg/ml, respectively. The hexane extract decreased Bcr/Abl protein expression in K562 cells by 74.6% and WT1 protein expressions in Molt4 and K562 cells by 68.4 and 72.1%, respectively. Total cell numbers were decreased by 66.2 and 48.7% in Molt4 and K562 cells, respectively. Mammea E/BB (main active compound) significantly decreased both Bcr/Abl and WTlprotein expressions by 75 and 49.5%, respectively when compared to vehicle control. CONCLUSION: The hexane fraction from flowers inhibited cell proliferation the suppression of WT1 expression in Molt4 and K562 cells and Bcr/Abl expression in K562 cells. The active compound may be mammea E/BB. Extracts from flowers show promise as naturally occurring anti-cancer drugs.
[Mh] Termos MeSH primário: Antineoplásicos Fitogênicos/uso terapêutico
Proteínas de Fusão bcr-abl/metabolismo
Leucemia/tratamento farmacológico
Mammea
Fitoterapia
Extratos Vegetais/uso terapêutico
Proteínas WT1/metabolismo
[Mh] Termos MeSH secundário: Antineoplásicos Fitogênicos/farmacologia
Proliferação Celular
Flores
Seres Humanos
Células K562
Leucemia/metabolismo
Medicina Tradicional
Proteínas Oncogênicas v-abl/metabolismo
Extratos Vegetais/farmacologia
Proteínas Proto-Oncogênicas c-bcr/metabolismo
Tailândia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents, Phytogenic); 0 (Oncogene Proteins v-abl); 0 (Plant Extracts); 0 (WT1 Proteins); 0 (WT1 protein, human); 0 (abl-bcr fusion protein, human); EC 2.7.10.2 (Fusion Proteins, bcr-abl); EC 2.7.11.1 (BCR protein, human); EC 2.7.11.1 (Proto-Oncogene Proteins c-bcr)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170816
[Lr] Data última revisão:
170816
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170603
[St] Status:MEDLINE
[do] DOI:10.21010/ajtcam.v14i2.3


  2 / 230 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:27748288
[Au] Autor:Nandagopalan SR; Kuila N; Biswas S; Pattnayak NC; Biswas G; Chakraborty S
[Ad] Endereço:Institute of Life Sciences, Bhubaneswar, Odisha, India.
[Ti] Título:Dual transcripts of - & different polymorphisms in chronic myeloid leukaemia patients.
[So] Source:Indian J Med Res;143(Supplement):S136-S141, 2016 May.
[Is] ISSN:0971-5916
[Cp] País de publicação:India
[La] Idioma:eng
[Ab] Resumo:BACKGROUND & OBJECTIVES: Chronic myeloid leukaemia is (CML) characterized by the presence of a hallmark chromosomal translocation, the Philadelphia chromosome. Although there are many reports available regarding the different variants of BCR-ABL in CML, we studied the co-expression of e13a2 and e14a2 transcripts and a few polymorphisms in CML patients. METHODS: Molecular genetics approach was adapted to screen for polymorphisms, mutation and translocation in BCR, ABL kinase domain and BCR-ABL breakpoint region in 73 CML patients. RESULTS: All eight patients with dual transcripts were found to harbour an exonic polymorphism (c.2700 T>C) and an intronic polymorphism (g.109366A>G) that were earlier reported to be associated with co-expression of both the transcripts. We also observed c.763G>A mutation in ABL kinase domain and two polymorphisms, c.2387 A>G and c.2736A>G in the BCR gene. INTERPRETATION & CONCLUSIONS: Though our data support the previous findings that co-expression of BCR-ABL transcripts is due to the occurrence of exonic and intronic polymorphisms in the BCR gene, it also shows that the intronic polymorphism can arise without the linked exonic polymorphism. The occurrence of ABL kinase domain mutation is less frequent in Indian population.
[Mh] Termos MeSH primário: Proteínas de Fusão bcr-abl/genética
Leucemia Mielogênica Crônica BCR-ABL Positiva/genética
Proteínas Oncogênicas v-abl/genética
Proteínas Proto-Oncogênicas c-bcr/genética
Translocação Genética/genética
[Mh] Termos MeSH secundário: Adulto
Éxons/genética
Feminino
Seres Humanos
Índia
Íntrons/genética
Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia
Masculino
Meia-Idade
Mutação
Cromossomo Filadélfia
Polimorfismo Genético
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Oncogene Proteins v-abl); EC 2.7.10.2 (Fusion Proteins, bcr-abl); EC 2.7.11.1 (BCR protein, human); EC 2.7.11.1 (Proto-Oncogene Proteins c-bcr)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170817
[Lr] Data última revisão:
170817
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161018
[St] Status:MEDLINE
[do] DOI:10.4103/0971-5916.191816


  3 / 230 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:27666407
[Au] Autor:Huang T; Zhou F; Wang-Johanning F; Nan K; Wei Y
[Ad] Endereço:Department of Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
[Ti] Título:Depression accelerates the development of gastric cancer through reactive oxygen species­activated ABL1 (Review).
[So] Source:Oncol Rep;36(5):2435-2443, 2016 Nov.
[Is] ISSN:1791-2431
[Cp] País de publicação:Greece
[La] Idioma:eng
[Ab] Resumo:Depression is a common symptom among gastric cancer (GC) patients and serves as a potential indication of poor prognosis and advanced cancer clinical stage. However, the molecular mechanism of depression­associated poor prognoses of GC patients remains unclear. Recent studies have revealed that GC patients with depression are under high levels of oxidative stress (OS) status that is accompanied by the dysfunction of numerous proto­oncogenes, including the ABL proto­oncogene 1 (ABL1), which is a non­receptor tyrosine kinase. Recent evidence indicates that ABL1 was dysregulated in both major depressive disorder (MDD) and cancer patients with depression, and high levels of reactive oxygen species (ROS) can lead to the activation of ABL1 in response to OS and that activated ABL1 subsequently contributes to development of GC via interactions with the downstream targets and corresponding signaling pathways. In this review, we examine the evidence to illuminate the molecular mechanism of ABL1 in the progression of GC patients with depression and identify out new and effective methods for the initial and long­term treatment of GC.
[Mh] Termos MeSH primário: Transtorno Depressivo/genética
Proteínas Oncogênicas v-abl/biossíntese
Neoplasias Gástricas/genética
[Mh] Termos MeSH secundário: Transtorno Depressivo/tratamento farmacológico
Transtorno Depressivo/etiologia
Transtorno Depressivo/patologia
Regulação Neoplásica da Expressão Gênica
Seres Humanos
Proteínas Oncogênicas v-abl/genética
Estresse Oxidativo/genética
Prognóstico
Espécies Reativas de Oxigênio
Neoplasias Gástricas/complicações
Neoplasias Gástricas/tratamento farmacológico
Neoplasias Gástricas/psicologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Oncogene Proteins v-abl); 0 (Reactive Oxygen Species)
[Em] Mês de entrada:1703
[Cu] Atualização por classe:170310
[Lr] Data última revisão:
170310
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160927
[St] Status:MEDLINE
[do] DOI:10.3892/or.2016.5127


  4 / 230 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:27601299
[Au] Autor:Lescale C; Lenden Hasse H; Blackford AN; Balmus G; Bianchi JJ; Yu W; Bacoccina L; Jarade A; Clouin C; Sivapalan R; Reina-San-Martin B; Jackson SP; Deriano L
[Ad] Endereço:Departments of Immunology and Genomes and Genetics, Institut Pasteur, 75015 Paris, France.
[Ti] Título:Specific Roles of XRCC4 Paralogs PAXX and XLF during V(D)J Recombination.
[So] Source:Cell Rep;16(11):2967-2979, 2016 Sep 13.
[Is] ISSN:2211-1247
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Paralog of XRCC4 and XLF (PAXX) is a member of the XRCC4 superfamily and plays a role in nonhomologous end-joining (NHEJ), a DNA repair pathway critical for lymphocyte antigen receptor gene assembly. Here, we find that the functions of PAXX and XLF in V(D)J recombination are masked by redundant joining activities. Thus, combined PAXX and XLF deficiency leads to an inability to join RAG-cleaved DNA ends. Additionally, we demonstrate that PAXX function in V(D)J recombination depends on its interaction with Ku. Importantly, we show that, unlike XLF, the role of PAXX during the repair of DNA breaks does not overlap with ATM and the RAG complex. Our findings illuminate the role of PAXX in V(D)J recombination and support a model in which PAXX and XLF function during NHEJ repair of DNA breaks, whereas XLF, the RAG complex, and the ATM-dependent DNA damage response promote end joining by stabilizing DNA ends.
[Mh] Termos MeSH primário: Linfócitos B/metabolismo
Enzimas Reparadoras do DNA/metabolismo
Proteínas de Ligação a DNA/química
Homologia de Sequência de Aminoácidos
Recombinação V(D)J/genética
[Mh] Termos MeSH secundário: Animais
Proteínas Mutadas de Ataxia Telangiectasia/metabolismo
Sistemas CRISPR-Cas/genética
Dano ao DNA
Reparo do DNA
Proteínas de Ligação a DNA/metabolismo
Deleção de Genes
Edição de Genes
Rearranjo Gênico do Linfócito B
Imunoglobulinas/genética
Autoantígeno Ku/metabolismo
Modelos Biológicos
Proteínas Oncogênicas v-abl/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (DNA-Binding Proteins); 0 (IgK); 0 (Immunoglobulins); 0 (Oncogene Proteins v-abl); EC 2.7.11.1 (Ataxia Telangiectasia Mutated Proteins); EC 4.2.99.- (Ku Autoantigen); EC 6.5.1.- (DNA Repair Enzymes)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171113
[Lr] Data última revisão:
171113
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160908
[St] Status:MEDLINE


  5 / 230 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:27241634
[Au] Autor:Haldane A; Flynn WF; He P; Vijayan RS; Levy RM
[Ad] Endereço:Department of Chemistry, Center for Biophysics and Computational Biology, Institute for Computational Molecular Science, Temple University, Philadelphia, Pennsylvania, 19122.
[Ti] Título:Structural propensities of kinase family proteins from a Potts model of residue co-variation.
[So] Source:Protein Sci;25(8):1378-84, 2016 08.
[Is] ISSN:1469-896X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Understanding the conformational propensities of proteins is key to solving many problems in structural biology and biophysics. The co-variation of pairs of mutations contained in multiple sequence alignments of protein families can be used to build a Potts Hamiltonian model of the sequence patterns which accurately predicts structural contacts. This observation paves the way to develop deeper connections between evolutionary fitness landscapes of entire protein families and the corresponding free energy landscapes which determine the conformational propensities of individual proteins. Using statistical energies determined from the Potts model and an alignment of 2896 PDB structures, we predict the propensity for particular kinase family proteins to assume a "DFG-out" conformation implicated in the susceptibility of some kinases to type-II inhibitors, and validate the predictions by comparison with the observed structural propensities of the corresponding proteins and experimental binding affinity data. We decompose the statistical energies to investigate which interactions contribute the most to the conformational preference for particular sequences and the corresponding proteins. We find that interactions involving the activation loop and the C-helix and HRD motif are primarily responsible for stabilizing the DFG-in state. This work illustrates how structural free energy landscapes and fitness landscapes of proteins can be used in an integrated way, and in the context of kinase family proteins, can potentially impact therapeutic design strategies.
[Mh] Termos MeSH primário: Proteína Quinase 14 Ativada por Mitógeno/antagonistas & inibidores
Proteínas Oncogênicas v-abl/antagonistas & inibidores
Inibidores de Proteínas Quinases/química
[Mh] Termos MeSH secundário: Motivos de Aminoácidos
Bases de Dados de Proteínas
Seres Humanos
Cinética
Ligantes
Proteína Quinase 14 Ativada por Mitógeno/química
Modelos Moleculares
Proteínas Oncogênicas v-abl/química
Ligação Proteica
Domínios Proteicos
Estrutura Secundária de Proteína
Homologia Estrutural de Proteína
Termodinâmica
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (Ligands); 0 (Oncogene Proteins v-abl); 0 (Protein Kinase Inhibitors); EC 2.7.11.24 (Mitogen-Activated Protein Kinase 14)
[Em] Mês de entrada:1704
[Cu] Atualização por classe:170801
[Lr] Data última revisão:
170801
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160601
[St] Status:MEDLINE
[do] DOI:10.1002/pro.2954


  6 / 230 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:26864341
[Au] Autor:Dasgupta Y; Koptyra M; Hoser G; Kantekure K; Roy D; Gornicka B; Nieborowska-Skorska M; Bolton-Gillespie E; Cerny-Reiterer S; Müschen M; Valent P; Wasik MA; Richardson C; Hantschel O; van der Kuip H; Stoklosa T; Skorski T
[Ad] Endereço:Department of Microbiology & Immunology, Temple University School of Medicine, Philadelphia, PA;
[Ti] Título:Normal ABL1 is a tumor suppressor and therapeutic target in human and mouse leukemias expressing oncogenic ABL1 kinases.
[So] Source:Blood;127(17):2131-43, 2016 Apr 28.
[Is] ISSN:1528-0020
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Leukemias expressing constitutively activated mutants of ABL1 tyrosine kinase (BCR-ABL1, TEL-ABL1, NUP214-ABL1) usually contain at least 1 normal ABL1 allele. Because oncogenic and normal ABL1 kinases may exert opposite effects on cell behavior, we examined the role of normal ABL1 in leukemias induced by oncogenic ABL1 kinases. BCR-ABL1-Abl1(-/-) cells generated highly aggressive chronic myeloid leukemia (CML)-blast phase-like disease in mice compared with less malignant CML-chronic phase-like disease from BCR-ABL1-Abl1(+/+) cells. Additionally, loss of ABL1 stimulated proliferation and expansion of BCR-ABL1 murine leukemia stem cells, arrested myeloid differentiation, inhibited genotoxic stress-induced apoptosis, and facilitated accumulation of chromosomal aberrations. Conversely, allosteric stimulation of ABL1 kinase activity enhanced the antileukemia effect of ABL1 tyrosine kinase inhibitors (imatinib and ponatinib) in human and murine leukemias expressing BCR-ABL1, TEL-ABL1, and NUP214-ABL1. Therefore, we postulate that normal ABL1 kinase behaves like a tumor suppressor and therapeutic target in leukemias expressing oncogenic forms of the kinase.
[Mh] Termos MeSH primário: Crise Blástica/genética
Genes Supressores de Tumor
Genes abl
Leucemia Experimental/genética
Leucemia Mieloide de Fase Crônica/genética
Proteínas Oncogênicas v-abl/fisiologia
Proteínas de Fusão Oncogênicas/fisiologia
Proteínas Proto-Oncogênicas c-abl/fisiologia
Proteínas Supressoras de Tumor/fisiologia
[Mh] Termos MeSH secundário: Animais
Antineoplásicos/farmacologia
Antineoplásicos/uso terapêutico
Apoptose/efeitos dos fármacos
Crise Blástica/tratamento farmacológico
Crise Blástica/enzimologia
Crise Blástica/patologia
Divisão Celular/efeitos dos fármacos
Linhagem Celular Tumoral
Citostáticos/farmacologia
Regulação Leucêmica da Expressão Gênica/efeitos dos fármacos
Instabilidade Genômica
Seres Humanos
Mesilato de Imatinib/farmacologia
Mesilato de Imatinib/uso terapêutico
Imidazóis/farmacologia
Imidazóis/uso terapêutico
Leucemia Experimental/tratamento farmacológico
Leucemia Experimental/enzimologia
Leucemia Experimental/patologia
Leucemia Mieloide de Fase Crônica/tratamento farmacológico
Leucemia Mieloide de Fase Crônica/enzimologia
Leucemia Mieloide de Fase Crônica/patologia
Camundongos
Camundongos Endogâmicos NOD
Camundongos SCID
Proteínas de Neoplasias/antagonistas & inibidores
Proteínas de Neoplasias/genética
Proteínas de Neoplasias/fisiologia
Células-Tronco Neoplásicas/efeitos dos fármacos
Células-Tronco Neoplásicas/enzimologia
Proteínas Oncogênicas v-abl/antagonistas & inibidores
Proteínas Oncogênicas v-abl/genética
Proteínas de Fusão Oncogênicas/antagonistas & inibidores
Proteínas de Fusão Oncogênicas/genética
Estresse Oxidativo
Inibidores de Proteínas Quinases/farmacologia
Inibidores de Proteínas Quinases/uso terapêutico
Proteínas Proto-Oncogênicas c-abl/genética
Piridazinas/farmacologia
Piridazinas/uso terapêutico
Proteínas Supressoras de Tumor/antagonistas & inibidores
Proteínas Supressoras de Tumor/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Cytostatic Agents); 0 (Imidazoles); 0 (Neoplasm Proteins); 0 (Oncogene Proteins v-abl); 0 (Oncogene Proteins, Fusion); 0 (Protein Kinase Inhibitors); 0 (Pyridazines); 0 (Tumor Suppressor Proteins); 4340891KFS (ponatinib); 8A1O1M485B (Imatinib Mesylate); EC 2.7.10.2 (Proto-Oncogene Proteins c-abl)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170713
[Lr] Data última revisão:
170713
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:160212
[St] Status:MEDLINE
[do] DOI:10.1182/blood-2015-11-681171


  7 / 230 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
PubMed Central Texto completo
Texto completo
[PMID]:26656091
[Au] Autor:Saleh T; Jankowski W; Sriram G; Rossi P; Shah S; Lee KB; Cruz LA; Rodriguez AJ; Birge RB; Kalodimos CG
[Ad] Endereço:Department of Biochemistry, Molecular Biology &Biophysics, University of Minnesota, Minneapolis, Minnesota, USA.
[Ti] Título:Cyclophilin A promotes cell migration via the Abl-Crk signaling pathway.
[So] Source:Nat Chem Biol;12(2):117-23, 2016 Feb.
[Is] ISSN:1552-4469
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Cyclophilin A (CypA) is overexpressed in a number of human cancer types, but the mechanisms by which the protein promotes oncogenic properties of cells are not understood. Here we demonstrate that CypA binds the CrkII adaptor protein and prevents it from switching to the inhibited state. CrkII influences cell motility and invasion by mediating signaling through its SH2 and SH3 domains. CrkII Tyr221 phosphorylation by the Abl or EGFR kinases induces an inhibited state of CrkII by means of an intramolecular SH2-pTyr221 interaction, causing signaling interruption. We show that the CrkII phosphorylation site constitutes a binding site for CypA. Recruitment of CypA sterically restricts the accessibility of Tyr221 to kinases, thereby suppressing CrkII phosphorylation and promoting the active state. Structural, biophysical and in vivo data show that CypA augments CrkII-mediated signaling. A strong stimulation of cell migration is observed in cancer cells wherein both CypA and CrkII are greatly upregulated.
[Mh] Termos MeSH primário: Ciclofilina A/farmacologia
Proteínas Oncogênicas v-abl/metabolismo
Proteínas Proto-Oncogênicas c-crk/metabolismo
Transdução de Sinais/efeitos dos fármacos
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Western Blotting
Calorimetria
Linhagem Celular Tumoral
Movimento Celular/efeitos dos fármacos
Seres Humanos
Dados de Sequência Molecular
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Oncogene Proteins v-abl); 0 (Proto-Oncogene Proteins c-crk); EC 5.2.1.- (Cyclophilin A)
[Em] Mês de entrada:1606
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:151215
[St] Status:MEDLINE
[do] DOI:10.1038/nchembio.1981


  8 / 230 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
PubMed Central Texto completo
Texto completo
[PMID]:26126715
[Au] Autor:Tu CC; Zhong Y; Nguyen L; Tsai A; Sridevi P; Tarn WY; Wang JY
[Ad] Endereço:Moores Cancer Center and Division of Hematology-Oncology, Department of Medicine, University of California, San Diego, La Jolla, CA 92093-0644, USA. Institute of Biomedical Sciences, Academia Sinica, Taipei 11529 Taiwan.
[Ti] Título:The kinase ABL phosphorylates the microprocessor subunit DGCR8 to stimulate primary microRNA processing in response to DNA damage.
[So] Source:Sci Signal;8(383):ra64, 2015 Jun 30.
[Is] ISSN:1937-9145
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The DNA damage response network stimulates microRNA (miRNA) biogenesis to coordinate repair, cell cycle checkpoints, and apoptosis. The multistep process of miRNA biogenesis involves the cleavage of primary miRNAs by the microprocessor complex composed of the ribonuclease Drosha and the RNA binding protein DGCR8. We found that the tyrosine kinase ABL phosphorylated DGCR8, a modification that was required for the induction of a subset of miRNAs after DNA damage. Focusing on the miR-34 family, ABL stimulated the production of miR-34c, but not miR-34a, through Drosha/DGCR8-dependent processing of primary miR-34c (pri-miR-34c). This miRNA-selective effect of ABL required the sequences flanking the precursor miR-34c (pre-miR-34c) stem-loop. In pri-miRNA processing, DGCR8 binds the pre-miR stem-loop and recruits Drosha to the miRNA. RNA cross-linking assays showed that DGCR8 and Drosha interacted with pri-miR-34c, but we found an inverse correlation between ABL-stimulated processing and DGCR8 association with pri-miR-34c. When coexpressed in HEK293T cells, ABL phosphorylated DGCR8 at Tyr(267). Ectopic expression of a Y267F-DGCR8 mutant reduced the recruitment of Drosha to pri-miR-34c and prevented ABL or Drosha from stimulating the processing of pri-miR-34c. In mice engineered to express a nuclear import-defective mutant of ABL, miR-34c, but not miR-34a, expression was reduced in the kidney, and apoptosis of the renal epithelial cells was impaired in response to cisplatin. These results reveal a new pathway in the DNA damage response wherein ABL-dependent tyrosine phosphorylation of DGCR8 stimulates the processing of selective primary miRNAs.
[Mh] Termos MeSH primário: Dano ao DNA
MicroRNAs/metabolismo
Proteínas Oncogênicas v-abl/metabolismo
Processamento Pós-Transcricional do RNA/fisiologia
Proteínas de Ligação a RNA/metabolismo
[Mh] Termos MeSH secundário: Animais
Seres Humanos
Camundongos
MicroRNAs/genética
Proteínas Oncogênicas v-abl/genética
Fosforilação/fisiologia
Proteínas de Ligação a RNA/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (DGCR8 protein, human); 0 (Dgcr8 protein, mouse); 0 (MIRN34 microRNA, human); 0 (MIRN34 microRNA, mouse); 0 (MicroRNAs); 0 (Oncogene Proteins v-abl); 0 (RNA-Binding Proteins)
[Em] Mês de entrada:1603
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150702
[St] Status:MEDLINE
[do] DOI:10.1126/scisignal.aaa4468


  9 / 230 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
PubMed Central Texto completo
Texto completo
[PMID]:25999467
[Au] Autor:Ting PY; Johnson CW; Fang C; Cao X; Graeber TG; Mattos C; Colicelli J
[Ad] Endereço:*Molecular Biology Institute, Jonsson Comprehensive Cancer Center, Department of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA; Department of Chemistry and Chemical Biology, Northeastern University, Boston, Massachusetts, U
[Ti] Título:Tyrosine phosphorylation of RAS by ABL allosterically enhances effector binding.
[So] Source:FASEB J;29(9):3750-61, 2015 Sep.
[Is] ISSN:1530-6860
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:RAS proteins are signal transduction gatekeepers that mediate cell growth, survival, and differentiation through interactions with multiple effector proteins. The RAS effector RAS- and RAB-interacting protein 1 (RIN1) activates its own downstream effectors, the small GTPase RAB5 and the tyrosine kinase Abelson tyrosine-protein kinase (ABL), to modulate endocytosis and cytoskeleton remodeling. To identify ABL substrates downstream of RAS-to-RIN1 signaling, we examined human HEK293T cells overexpressing components of this pathway. Proteomic analysis revealed several novel phosphotyrosine peptides, including Harvey rat sarcoma oncogene (HRAS)-pTyr(137). Here we report that ABL phosphorylates tyrosine 137 of H-, K-, and NRAS. Increased RIN1 levels enhanced HRAS-Tyr(137) phosphorylation by nearly 5-fold, suggesting that RAS-stimulated RIN1 can drive ABL-mediated RAS modification in a feedback circuit. Tyr(137) is well conserved among RAS orthologs and is part of a transprotein H-bond network. Crystal structures of HRAS(Y137F) and HRAS(Y137E) revealed conformation changes radiating from the mutated residue. Although consistent with Tyr(137) participation in allosteric control of HRAS function, the mutations did not alter intrinsic GTP hydrolysis rates in vitro. HRAS-Tyr(137) phosphorylation enhanced HRAS signaling capacity in cells, however, as reflected by a 4-fold increase in the association of phosphorylated HRAS(G12V) with its effector protein RAF proto-oncogene serine/threonine protein kinase 1 (RAF1). These data suggest that RAS phosphorylation at Tyr(137) allosterically alters protein conformation and effector binding, providing a mechanism for effector-initiated modulation of RAS signaling.
[Mh] Termos MeSH primário: Proteínas Oncogênicas v-abl/metabolismo
Proteínas Proto-Oncogênicas p21(ras)/metabolismo
Transdução de Sinais/fisiologia
[Mh] Termos MeSH secundário: Substituição de Aminoácidos
Animais
Células HEK293
Seres Humanos
Peptídeos e Proteínas de Sinalização Intracelular/química
Peptídeos e Proteínas de Sinalização Intracelular/genética
Peptídeos e Proteínas de Sinalização Intracelular/metabolismo
Mutação de Sentido Incorreto
Proteínas Oncogênicas v-abl/química
Proteínas Oncogênicas v-abl/genética
Fosforilação/genética
Proteínas Proto-Oncogênicas p21(ras)/química
Proteínas Proto-Oncogênicas p21(ras)/genética
Ratos
Tirosina/química
Tirosina/genética
Tirosina/metabolismo
Proteínas rab5 de Ligação ao GTP/química
Proteínas rab5 de Ligação ao GTP/genética
Proteínas rab5 de Ligação ao GTP/metabolismo
Quinases raf/química
Quinases raf/genética
Quinases raf/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T; RESEARCH SUPPORT, U.S. GOV'T, NON-P.H.S.
[Nm] Nome de substância:
0 (Intracellular Signaling Peptides and Proteins); 0 (Oncogene Proteins v-abl); 0 (RIN1 protein, human); 42HK56048U (Tyrosine); EC 2.7.11.1 (raf Kinases); EC 3.6.1.- (RAB5C protein, human); EC 3.6.5.2 (Proto-Oncogene Proteins p21(ras)); EC 3.6.5.2 (rab5 GTP-Binding Proteins)
[Em] Mês de entrada:1511
[Cu] Atualização por classe:161228
[Lr] Data última revisão:
161228
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150523
[St] Status:MEDLINE
[do] DOI:10.1096/fj.15-271510


  10 / 230 MEDLINE  
              first record previous record
seleciona
para imprimir
Fotocópia
PubMed Central Texto completo
Texto completo
[PMID]:25917813
[Au] Autor:Felgentreff K; Lee YN; Frugoni F; Du L; van der Burg M; Giliani S; Tezcan I; Reisli I; Mejstrikova E; de Villartay JP; Sleckman BP; Manis J; Notarangelo LD
[Ad] Endereço:Division of Immunology, Boston Children's Hospital, Harvard Medical School, Boston, Mass.
[Ti] Título:Functional analysis of naturally occurring DCLRE1C mutations and correlation with the clinical phenotype of ARTEMIS deficiency.
[So] Source:J Allergy Clin Immunol;136(1):140-150.e7, 2015 Jul.
[Is] ISSN:1097-6825
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: The endonuclease ARTEMIS, which is encoded by the DCLRE1C gene, is a component of the nonhomologous end-joining pathway and participates in hairpin opening during the V(D)J recombination process and repair of a subset of DNA double-strand breaks. Patients with ARTEMIS deficiency usually present with severe combined immunodeficiency (SCID) and cellular radiosensitivity, but hypomorphic mutations can cause milder phenotypes (leaky SCID). OBJECTIVE: We sought to correlate the functional effect of human DCLRE1C mutations on phenotypic presentation in patients with ARTEMIS deficiency. METHODS: We studied the recombination and DNA repair activity of 41 human DCLRE1C mutations in Dclre1c(-/-) v-abl kinase-transformed pro-B cells retrovirally engineered with a construct that allows quantification of recombination activity by means of flow cytometry. For assessment of DNA repair efficacy, resolution of γH2AX accumulation was studied after ionizing radiation. RESULTS: Low or absent activity was detected for mutations causing a typical SCID phenotype. Most of the patients with leaky SCID were compound heterozygous for 1 loss-of-function and 1 hypomorphic allele, with significant residual levels of recombination and DNA repair activity. Deletions disrupting the C-terminus result in truncated but partially functional proteins and are often associated with leaky SCID. Overexpression of hypomorphic mutants might improve the functional defect. CONCLUSIONS: Correlation between the nature and location of DCLRE1C mutations, functional activity, and the clinical phenotype has been observed. Hypomorphic variants that have been reported in the general population can be disease causing if combined in trans with a loss-of-function allele. Therapeutic strategies aimed at inducing overexpression of hypomorphic alleles might be beneficial.
[Mh] Termos MeSH primário: Linfócitos B/fisiologia
Mutação/genética
Proteínas Nucleares/genética
Imunodeficiência Combinada Severa/genética
[Mh] Termos MeSH secundário: Adolescente
Adulto
Alelos
Linfócitos B/efeitos da radiação
Linhagem Celular Transformada
Criança
Pré-Escolar
Análise Mutacional de DNA
Reparo do DNA/genética
Endonucleases
Heterozigoto
Histonas/metabolismo
Seres Humanos
Lactente
Recém-Nascido
Masculino
Proteínas Oncogênicas v-abl/genética
Proteínas Oncogênicas v-abl/metabolismo
Fenótipo
Tolerância a Radiação/genética
Radiação Ionizante
Recombinação V(D)J/genética
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (H2AFX protein, human); 0 (Histones); 0 (Nuclear Proteins); 0 (Oncogene Proteins v-abl); EC 3.1.- (DCLRE1C protein, human); EC 3.1.- (Endonucleases)
[Em] Mês de entrada:1510
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:150429
[St] Status:MEDLINE



página 1 de 23 ir para página                         
   


Refinar a pesquisa
  Base de dados : MEDLINE Formulário avançado   

    Pesquisar no campo  
1  
2
3
 
           



Search engine: iAH v2.6 powered by WWWISIS

BIREME/OPAS/OMS - Centro Latino-Americano e do Caribe de Informação em Ciências da Saúde