Base de dados : MEDLINE
Pesquisa : D12.644.360.325.150.500 [Categoria DeCS]
Referências encontradas : 1510 [refinar]
Mostrando: 1 .. 10   no formato [Detalhado]

página 1 de 151 ir para página                         

  1 / 1510 MEDLINE  
              next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28469997
[Au] Autor:Zhao M; Zhang L; Lv S; Zhang C; Wang L; Chen H; Zhou Y; Lou J
[Ad] Endereço:Department of Laboratory Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong UniversityShanghai, China.
[Ti] Título:IQGAP1 Mediates Hcp1-Promoted Meningitis by Stimulating the MAPK Pathway.
[So] Source:Front Cell Infect Microbiol;7:132, 2017.
[Is] ISSN:2235-2988
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:-induced meningitis remains a life-threatening disease despite recent advances in the field of antibiotics-based therapeutics, necessitating continued research on its pathogenesis. The current study aims to elucidate the mechanism through which hemolysin-coregulated protein 1 (Hcp1) induces the apoptosis of human brain microvascular endothelial cells (HBMEC). Co-immunoprecipitation coupled with mass spectrometric (MS) characterization led to the identification of IQ motif containing GTPase activating protein 1 (IQGAP1) as a downstream target of Hcp1. IQGAP1 was found to be up-regulated by Hcp1 treatment and mediate the stimulation of HBMEC apoptosis. It was shown that Hcp1 could compete against Smurf1 for binding to IQGAP1, thereby rescuing the latter from ubiquitin-dependent degradation. Subsequent study suggested that IQGAP1 could stimulate the MAPK signaling pathway by promoting the phosphorylation of ERK1/2, an effect that was blocked by U0126, an MAPK inhibitor. Furthermore, U0126 also demonstrated therapeutic potential against meningitis in a mouse model. Taken together, our results suggested the feasibility of targeting the MAPK pathway as a putative therapeutic strategy against bacterial meningitis.
[Mh] Termos MeSH primário: Proteínas de Escherichia coli/farmacologia
Escherichia coli/metabolismo
Meningite devida a Escherichia coli/metabolismo
Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo
Fatores de Virulência/farmacologia
Proteínas Ativadoras de ras GTPase/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Apoptose/efeitos dos fármacos
Encéfalo
Butadienos/antagonistas & inibidores
Linhagem Celular
Citocinas/análise
Modelos Animais de Doenças
Células Endoteliais/efeitos dos fármacos
Seres Humanos
Meningite devida a Escherichia coli/tratamento farmacológico
Camundongos
Camundongos Endogâmicos C57BL
Proteína Quinase 3 Ativada por Mitógeno/metabolismo
Nitrilos/antagonistas & inibidores
Fosforilação
RNA Interferente Pequeno
Transdução de Sinais
Ubiquitina-Proteína Ligases
Regulação para Cima
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Butadienes); 0 (Cytokines); 0 (Escherichia coli Proteins); 0 (HCP1 protein, E coli); 0 (IQ motif containing GTPase activating protein 1); 0 (Nitriles); 0 (RNA, Small Interfering); 0 (U 0126); 0 (Virulence Factors); 0 (ras GTPase-Activating Proteins); EC 2.3.2.26 (SMURF1 protein, human); EC 2.3.2.27 (Ubiquitin-Protein Ligases); EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3); EC 2.7.12.2 (Mitogen-Activated Protein Kinase Kinases)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:180216
[Lr] Data última revisão:
180216
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170505
[St] Status:MEDLINE
[do] DOI:10.3389/fcimb.2017.00132


  2 / 1510 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29291408
[Au] Autor:Muro R; Nitta T; Kitajima M; Okada T; Suzuki H
[Ad] Endereço:Department of Immunology and Pathology, Research Institute, National Center for Global Health and Medicine, Chiba 272-8516, Japan.
[Ti] Título:Rasal3-mediated T cell survival is essential for inflammatory responses.
[So] Source:Biochem Biophys Res Commun;496(1):25-30, 2018 01 29.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Fine regulation of the Ras/mitogen-activating protein kinase (MAPK) pathway is crucial in controlling the survival, proliferation, and development of various types of cells. Ras-activating protein-like 3 (Rasal3) is a T cell-specific Ras GTPase-activating protein that negatively regulates T cell receptor (TCR)-induced activation of Ras/MAPK pathway. Rasal3-deficient mice showed a decreased number of naive T cells because Rasal3 is required for the survival of naive T cells. In the current study, we observed ameliorated Type1 T helper (Th1) cell- and Type2 T helper (Th2) cell-dependent contact hypersensitivity reactions in Rasal3-deficient mice, along with a marked shortage of T cells at regional lymph node. Activated Rasal3-deficient T cells showed an increased cell death with reduced Bcl2 expression, suggesting that Rasal3 is required for the survival of not only naïve T cells but also activated T cells. Collectively, Rasal3 controls the magnitude of inflammatory responses through the survival of both naive T cells and activated T cells in vivo.
[Mh] Termos MeSH primário: Sobrevivência Celular/imunologia
Dermatite de Contato/imunologia
Dermatite de Contato/patologia
Ativação Linfocitária/imunologia
Linfócitos T/imunologia
Proteínas Ativadoras de ras GTPase/imunologia
[Mh] Termos MeSH secundário: Animais
Camundongos
Camundongos Endogâmicos C57BL
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (RASAL3 protein, mouse); 0 (ras GTPase-Activating Proteins)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180214
[Lr] Data última revisão:
180214
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180102
[St] Status:MEDLINE


  3 / 1510 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29221435
[Au] Autor:König E; Volpato CB; Motta BM; Blankenburg H; Picard A; Pramstaller P; Casella M; Rauhe W; Pompilio G; Meraviglia V; Domingues FS; Sommariva E; Rossini A
[Ad] Endereço:Institute for Biomedicine, Eurac Research, Affiliated Institute of the University of Lübeck, Bolzano, Italy.
[Ti] Título:Exploring digenic inheritance in arrhythmogenic cardiomyopathy.
[So] Source:BMC Med Genet;18(1):145, 2017 12 08.
[Is] ISSN:1471-2350
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Arrhythmogenic cardiomyopathy (ACM) is an inherited genetic disorder, characterized by the substitution of heart muscle with fibro-fatty tissue and severe ventricular arrhythmias, often leading to heart failure and sudden cardiac death. ACM is considered a monogenic disorder, but the low penetrance of mutations identified in patients suggests the involvement of additional genetic or environmental factors. METHODS: We used whole exome sequencing to investigate digenic inheritance in two ACM families where previous diagnostic tests have revealed a PKP2 mutation in all affected and some healthy individuals. In family members with PKP2 mutations we determined all genes that harbor variants in affected but not in healthy carriers or vice versa. We computationally prioritized the most likely candidates, focusing on known ACM genes and genes related to PKP2 through protein interactions, functional relationships, or shared biological processes. RESULTS: We identified four candidate genes in family 1, namely DAG1, DAB2IP, CTBP2 and TCF25, and eleven candidate genes in family 2. The most promising gene in the second family is TTN, a gene previously associated with ACM, in which the affected individual harbors two rare deleterious-predicted missense variants, one of which is located in the protein's only serine kinase domain. CONCLUSIONS: In this study we report genes that might act as digenic players in ACM pathogenesis, on the basis of co-segregation with PKP2 mutations. Validation in larger cohorts is still required to prove the utility of this model.
[Mh] Termos MeSH primário: Displasia Arritmogênica Ventricular Direita/genética
[Mh] Termos MeSH secundário: Adulto
Idoso
Idoso de 80 Anos ou mais
Oxirredutases do Álcool/genética
Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética
Conectina/química
Conectina/genética
Distroglicanas/genética
Feminino
Seres Humanos
Masculino
Meia-Idade
Modelos Moleculares
Mutação
Proteínas do Tecido Nervoso/genética
Linhagem
Placofilinas/genética
Domínios Proteicos
Proteínas Repressoras/genética
Sequenciamento Completo do Exoma
Proteínas Ativadoras de ras GTPase/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Basic Helix-Loop-Helix Transcription Factors); 0 (Connectin); 0 (DAB2IP protein, human); 0 (DAG1 protein, human); 0 (Nerve Tissue Proteins); 0 (PKP2 protein, human); 0 (Plakophilins); 0 (Repressor Proteins); 0 (TCF25 protein, human); 0 (TTN protein, human); 0 (ras GTPase-Activating Proteins); 146888-27-9 (Dystroglycans); EC 1.1.- (Alcohol Oxidoreductases); EC 1.1.- (CTBP2 protein, human)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171231
[Lr] Data última revisão:
171231
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171210
[St] Status:MEDLINE
[do] DOI:10.1186/s12881-017-0503-7


  4 / 1510 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29240845
[Au] Autor:Reimer M; Denby E; Zustiak SP; Schober JM
[Ad] Endereço:Department of Pharmaceutical Sciences, Southern Illinois University Edwardsville, Edwardsville, Illinois, United States of America.
[Ti] Título:Ras GAP-related and C-terminal domain-dependent localization and tumorigenic activities of IQGAP1 in melanoma cells.
[So] Source:PLoS One;12(12):e0189589, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:IQGAP1 interacts with a number of binding partners through a calponin homology domain (CHD), a WW motif, IQ repeats, a Ras GAP-related domain (GRD), and a conserved C-terminal (CT) domain. Among various biological and cellular functions, IQGAP1 is known to play a role in actin cytoskeleton dynamics during membrane ruffling and lamellipodium protrusion. In addition, phosphorylation near the CT domain is thought to control IQGAP1 activity through regulation of intramolecular interaction. In a previous study, we discovered that IQGAP1 preferentially localizes to retracting areas in B16F10 mouse melanoma cells, not areas of membrane ruffling and lamellipodium protrusion. Nothing is known of the domains needed for retraction localization and very little is known of IQGAP1 function in the actin cytoskeleton of melanoma cells. Thus, we examined localization of IQGAP1 mutants to retracting areas, and characterized knock down phenotypes on tissue culture plastic and physiologic-stiffness hydrogels. Localization of IQGAP1 mutants (S1441E/S1443D, S1441A/S1443A, ΔCHD, ΔGRD or ΔCT) to retracting and protruding cell edges were measured. In retracting areas there was a decrease in S1441A/S1443A, ΔGRD and ΔCT localization, a minor decrease in ΔCHD localization, and normal localization of the S1441E/S1443D mutant. In areas of cell protrusion just behind the lamellipodium leading edge, we surprisingly observed both ΔGRD and ΔCT localization, and increased number of microtubules. IQGAP1 knock down caused loss of cell polarity on laminin-coated glass, decreased proliferation on tissue culture polystyrene, and abnormal spheroid growth on laminin-coated hydrogels. We propose that the GRD and CT domains regulate IQGAP1 localization to retracting actin networks to promote a tumorigenic role in melanoma cells.
[Mh] Termos MeSH primário: Melanoma Experimental/metabolismo
Proteínas Ativadoras de ras GTPase/metabolismo
[Mh] Termos MeSH secundário: Citoesqueleto de Actina/metabolismo
Animais
Carcinogênese
Linhagem Celular Tumoral
Técnicas de Silenciamento de Genes
Hidrogéis
Melanoma Experimental/patologia
Camundongos
Microtúbulos/metabolismo
Mutação
Pseudópodes/metabolismo
Proteínas Ativadoras de ras GTPase/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Hydrogels); 0 (IQ motif containing GTPase activating protein 1); 0 (ras GTPase-Activating Proteins)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171229
[Lr] Data última revisão:
171229
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171215
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0189589


  5 / 1510 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29073199
[Au] Autor:Kumar D; Hassan MK; Pattnaik N; Mohapatra N; Dixit M
[Ad] Endereço:School of Biological Sciences, National Institute of Science Education and Research, HBNI, Odisha, India.
[Ti] Título:Reduced expression of IQGAP2 and higher expression of IQGAP3 correlates with poor prognosis in cancers.
[So] Source:PLoS One;12(10):e0186977, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:IQGAPs is a family of proteins which comprises three members, in humans. The expression pattern and role of IQGAP1 has been well established in many cancers, whereas those of IQGAP2 and IQGAP3, have mostly remained unexplored. We used available large datasets, to explore the pan-cancer status of these two genes in-silico. Here we have analysed their mRNA expression and correlation with survivability in eight different cancers, including lung, breast, gastric, brain, colorectal, prostate, liver and kidney cancers and, their subtypes. The mRNA expression of IQGAP2 and IQGAP3 in individual cancers were analysed in two different publicly available databases viz. Oncomine and TCGA. The prognostic value of these genes in lung, breast and gastric cancer was analysed using Kaplan-Meier Plotter database, whereas for brain, colorectal, liver, prostate and kidney cancers, SurvExpress database was used. These results were validated by immunohistochemistry in cancer tissues (stomach, prostate, brain, colorectal). Moreover, we did IQGAP2 and IQGAP3 genomic alteration and, promoter methylation analysis using cBioportal and Wanderer web tool, respectively. Most of the cancer types (lung, breast, prostate, brain, gastric, liver, kidney and colorectal) showed increased IQGAP3 mRNA expression. In contrast, the IQGAP2 transcript levels were reduced across different cancers viz. lung, breast, gastric, liver, kidney and colorectal cancer. IQGAP2 expression correlated positively with survivability, on the contrary, IQGAP3 expression levels correlated inversely with survivability, in most of the cancers. Collectively, enhanced IQGAP3 and reduced IQGAP2 levels were frequently observed in multiple cancers with the former predicting poor survivability and the later opposite. Methylation pattern was significantly altered in most of the cancer types. We found copy no. variation and mutations in specific cancers, for IQGAP2 and IQGAP3. Our in-vivo (IHC) data confirmed the in-silico findings completely. Hence, IQGAP2 and IQGAP3 have potential to be used as prognostic markers or therapeutic targets in specific cancers.
[Mh] Termos MeSH primário: Proteínas Ativadoras de GTPase/genética
Regulação Neoplásica da Expressão Gênica
Neoplasias/diagnóstico
Neoplasias/genética
Proteínas Ativadoras de ras GTPase/genética
[Mh] Termos MeSH secundário: Biologia Computacional
Metilação de DNA
Mineração de Dados
Seres Humanos
Estadiamento de Neoplasias
Neoplasias/patologia
Prognóstico
Regiões Promotoras Genéticas/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (GTPase-Activating Proteins); 0 (IQGAP2 protein, human); 0 (IQGAP3 protein, human); 0 (ras GTPase-Activating Proteins)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171110
[Lr] Data última revisão:
171110
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171027
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0186977


  6 / 1510 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28970065
[Au] Autor:Itoh N; Nagai T; Watanabe T; Taki K; Nabeshima T; Kaibuchi K; Yamada K
[Ad] Endereço:Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8560, Japan; Department of Cell Pharmacology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8550, Jap
[Ti] Título:Valosin-containing protein (VCP) is a novel IQ motif-containing GTPase activating protein 1 (IQGAP1)-interacting protein.
[So] Source:Biochem Biophys Res Commun;493(4):1384-1389, 2017 Dec 02.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Scaffold proteins play a pivotal role in making protein complexes, and organize binding partners into a functional unit to enhance specific signaling pathways. IQ motif-containing GTPase activating protein 1 (IQGAP1) is an essential protein for spine formation due to its role in scaffolding multiple signal complexes. However, it remains unclear how IQGAP1 interacts within the brain. In the present study, we screened novel IQGAP1-interacting proteins by a proteomic approach. As a novel IQGAP1-interacting protein, we identified valosin-containing protein (VCP) which is a causative gene in patients with inclusion body myopathy with Paget's disease of bone and frontotemporal dementia (IBMPFD). The physiological interaction of IQGAP1 with VCP was confirmed by an immunoprecipitation assay. Both the N-terminal (N-half) and C-terminal (C-half) fragments of IQGAP1 interacted with the N-terminal region of VCP. Co-localization of IQGAP1 and VCP was observed in the growth corn, axonal shaft, cell body, and dendrites in cultured hippocampal neurons at 4 days in vitro (DIV4). In cultured neurons at DIV14, IQGAP1 co-localized with VCP in dendrites. When HEK293T cells were co-transfected with IQGAP1 and VCP, an immunoprecipitation assay revealed that binding of IQGAP1 with disease-related mutant (R155H or A232E) VCP was markedly reduced compared to wild-type (WT) VCP. These results suggest that reduction of IQGAP1 and VCP interaction may be associated with the pathophysiology of IBMPFD.
[Mh] Termos MeSH primário: Adenosina Trifosfatases/metabolismo
Proteínas de Ciclo Celular/metabolismo
Proteínas Ativadoras de ras GTPase/metabolismo
[Mh] Termos MeSH secundário: Adenosina Trifosfatases/química
Adenosina Trifosfatases/genética
Substituição de Aminoácidos
Proteínas de Ciclo Celular/química
Proteínas de Ciclo Celular/genética
Demência Frontotemporal/genética
Demência Frontotemporal/metabolismo
Células HEK293
Células HeLa
Hipocampo/metabolismo
Seres Humanos
Imuno-Histoquímica
Distrofia Muscular do Cíngulo dos Membros/genética
Distrofia Muscular do Cíngulo dos Membros/metabolismo
Mutagênese Sítio-Dirigida
Proteínas Mutantes/química
Proteínas Mutantes/genética
Proteínas Mutantes/metabolismo
Miosite de Corpos de Inclusão/genética
Miosite de Corpos de Inclusão/metabolismo
Neurônios/metabolismo
Osteíte Deformante/genética
Osteíte Deformante/metabolismo
Domínios e Motivos de Interação entre Proteínas
Proteômica
Proteínas Recombinantes/química
Proteínas Recombinantes/genética
Proteínas Recombinantes/metabolismo
Proteína com Valosina
Proteínas Ativadoras de ras GTPase/química
Proteínas Ativadoras de ras GTPase/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cell Cycle Proteins); 0 (IQ motif containing GTPase activating protein 1); 0 (Mutant Proteins); 0 (Recombinant Proteins); 0 (ras GTPase-Activating Proteins); EC 3.6.1.- (Adenosine Triphosphatases); EC 3.6.4.6 (VCP protein, human); EC 3.6.4.6 (Valosin Containing Protein)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171004
[St] Status:MEDLINE


  7 / 1510 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28912364
[Au] Autor:Zhang L; Chen Q; An W; Yang F; Maguire EM; Chen D; Zhang C; Wen G; Yang M; Dai B; Luong LA; Zhu J; Xu Q; Xiao Q
[Ad] Endereço:From the Department of Cardiology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China (L.Z., Q.C., F.Y., M.Y., B.D., J.Z., Q. Xu); Centre for Clinical Pharmacology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Ma
[Ti] Título:Novel Pathological Role of hnRNPA1 (Heterogeneous Nuclear Ribonucleoprotein A1) in Vascular Smooth Muscle Cell Function and Neointima Hyperplasia.
[So] Source:Arterioscler Thromb Vasc Biol;37(11):2182-2194, 2017 Nov.
[Is] ISSN:1524-4636
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: hnRNPA1 (heterogeneous nuclear ribonucleoprotein A1) plays a variety of roles in gene expression. However, little is known about the functional involvement of hnRNPA1 in vascular smooth muscle cell (VSMC) function and neointima hyperplasia. In this study, we have attempted to investigate the functional roles of hnRNPA1 in the contexts of VSMC function, injury-induced vessel remodeling, and human atherosclerotic lesions, as well as discern the molecular mechanisms involved. APPROACH AND RESULTS: hnRNPA1 expression levels were consistently modulated during VSMC phenotype switching and neointimal lesion formation induced by wire injury. Functional studies showed that VSMC-specific gene expression, proliferation, and migration were regulated by hnRNPA1. Our data show that hnRNPA1 exerts its effects on VSMC functions through modulation of IQGAP1 (IQ motif containing GTPase activating protein 1). Mechanistically, hnRNPA1 regulates IQGAP1 mRNA degradation through 2 mechanisms: upregulating microRNA-124 (miR-124) and binding to AU-rich element of IQGAP1 gene. Further evidence suggests that hnRNPA1 upregulates miR-124 by modulating miR-124 biogenesis and that IQGAP1 is the authentic target gene of miR-124. Importantly, ectopic overexpression of hnRNPA1 greatly reduced VSMC proliferation and inhibited neointima formation in wire-injured carotid arteries. Finally, lower expression levels of hnRNPA1 and miR-124, while higher expression levels of IQGAP1, were observed in human atherosclerotic lesions. CONCLUSIONS: Our data show that hnRNPA1 is a critical regulator of VSMC function and behavior in the context of neointima hyperplasia, and the hnRNPA1/miR-124/IQGAP1 regulatory axis represents a novel therapeutic target for the prevention of cardiovascular diseases.
[Mh] Termos MeSH primário: Lesões das Artérias Carótidas/metabolismo
Proliferação Celular
Ribonucleoproteínas Nucleares Heterogêneas Grupo A-B/metabolismo
Músculo Liso Vascular/metabolismo
Miócitos de Músculo Liso/metabolismo
Neointima
[Mh] Termos MeSH secundário: Regiões 3' não Traduzidas
Animais
Lesões das Artérias Carótidas/genética
Lesões das Artérias Carótidas/patologia
Artéria Carótida Primitiva/metabolismo
Artéria Carótida Primitiva/patologia
Movimento Celular
Células Cultivadas
Modelos Animais de Doenças
Regulação da Expressão Gênica
Ribonucleoproteína Nuclear Heterogênea A1
Ribonucleoproteínas Nucleares Heterogêneas Grupo A-B/genética
Hiperplasia
Masculino
Camundongos
Camundongos Endogâmicos C57BL
MicroRNAs/genética
MicroRNAs/metabolismo
Músculo Liso Vascular/lesões
Músculo Liso Vascular/patologia
Miócitos de Músculo Liso/patologia
Interferência de RNA
Transdução de Sinais
Fatores de Tempo
Transfecção
Proteínas Ativadoras de ras GTPase/genética
Proteínas Ativadoras de ras GTPase/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (3' Untranslated Regions); 0 (HNRPA1 protein, human); 0 (Heterogeneous Nuclear Ribonucleoprotein A1); 0 (Heterogeneous-Nuclear Ribonucleoprotein Group A-B); 0 (Hnrnpa1 protein, mouse); 0 (IQ motif containing GTPase activating protein 1); 0 (MicroRNAs); 0 (Mirn124 microRNA, mouse); 0 (ras GTPase-Activating Proteins)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171123
[Lr] Data última revisão:
171123
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170916
[St] Status:MEDLINE
[do] DOI:10.1161/ATVBAHA.117.310020


  8 / 1510 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28864474
[Au] Autor:Tocker AM; Durocher E; Jacob KD; Trieschman KE; Talento SM; Rechnitzer AA; Roberts DM; Davis BK
[Ad] Endereço:Department of Biology, Franklin and Marshall College, Lancaster, PA 17604.
[Ti] Título:The Scaffolding Protein IQGAP1 Interacts with NLRC3 and Inhibits Type I IFN Production.
[So] Source:J Immunol;199(8):2896-2909, 2017 Oct 15.
[Is] ISSN:1550-6606
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Sensing of cytosolic nucleotides is a critical initial step in the elaboration of type I IFN. One of several upstream receptors, cyclic GMP-AMP synthase, binds to cytosolic DNA and generates dicyclic nucleotides that act as secondary messengers. These secondary messengers bind directly to stimulator of IFN genes (STING). STING recruits TNFR-associated NF-κB kinase-binding kinase 1 which acts as a critical node that allows for efficient activation of IFN regulatory factors to drive the antiviral transcriptome. NLRC3 is a recently characterized nucleotide-binding domain, leucine-rich repeat containing protein (NLR) that negatively regulates the type I IFN pathway by inhibiting subcellular redistribution and effective signaling of STING, thus blunting the transcription of type I IFNs. NLRC3 is predominantly expressed in lymphoid and myeloid cells. IQGAP1 was identified as a putative interacting partner of NLRC3 through yeast two-hybrid screening. In this article, we show that IQGAP1 associates with NLRC3 and can disrupt the NLRC3-STING interaction in the cytosol of human epithelial cells. Furthermore, knockdown of IQGAP1 in THP1 and HeLa cells causes significantly more IFN-ß production in response to cytosolic nucleic acids. This result phenocopies NLRC3-deficient macrophages and fibroblasts and short hairpin RNA knockdown of NLRC3 in THP1 cells. Our findings suggest that IQGAP1 is a novel regulator of type I IFN production, possibly via interacting with NLRC3 in human monocytic and epithelial cells.
[Mh] Termos MeSH primário: Células Epiteliais/fisiologia
Peptídeos e Proteínas de Sinalização Intercelular/metabolismo
Macrófagos/fisiologia
Viroses/imunologia
Proteínas Ativadoras de ras GTPase/metabolismo
[Mh] Termos MeSH secundário: Células HEK293
Células HeLa
Seres Humanos
Imunidade
Interferon Tipo I/metabolismo
Proteínas de Membrana/metabolismo
Ácidos Nucleicos/imunologia
Ligação Proteica
RNA Interferente Pequeno/genética
Transdução de Sinais
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (IQ motif containing GTPase activating protein 1); 0 (Intercellular Signaling Peptides and Proteins); 0 (Interferon Type I); 0 (MPYS protein, human); 0 (Membrane Proteins); 0 (NLRC3 protein, human); 0 (Nucleic Acids); 0 (RNA, Small Interfering); 0 (ras GTPase-Activating Proteins)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171101
[Lr] Data última revisão:
171101
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170903
[St] Status:MEDLINE
[do] DOI:10.4049/jimmunol.1601370


  9 / 1510 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28739799
[Au] Autor:Carmon KS; Gong X; Yi J; Wu L; Thomas A; Moore CM; Masuho I; Timson DJ; Martemyanov KA; Liu QJ
[Ad] Endereço:From the Brown Foundation Institute of Molecular Medicine and Texas Therapeutics Institute, University of Texas Health Science Center, Houston, Texas 77030.
[Ti] Título:LGR5 receptor promotes cell-cell adhesion in stem cells and colon cancer cells via the IQGAP1-Rac1 pathway.
[So] Source:J Biol Chem;292(36):14989-15001, 2017 Sep 08.
[Is] ISSN:1083-351X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5) is a marker of adult stem cells in several epithelial tissues, most notably in the intestinal crypts, and is highly up-regulated in many colorectal, hepatocellular, and ovarian cancers. LGR5 activation by R-spondin (RSPO) ligands potentiates Wnt/ß-catenin signaling ; however, deletion of LGR5 in stem cells has little or no effect on Wnt/ß-catenin signaling or cell proliferation Remarkably, modulation of LGR5 expression has a major impact on the actin cytoskeletal structure and cell adhesion in the absence of RSPO stimulation, but the molecular mechanism is unclear. Here, we show that LGR5 interacts with IQ motif-containing GTPase-activating protein 1 (IQGAP1), an effector of Rac1/CDC42 GTPases, in the regulation of actin cytoskeleton dynamics and cell-cell adhesion. Specifically, LGR5 decreased levels of IQGAP1 phosphorylation at Ser-1441/1443, leading to increased binding of Rac1 to IQGAP1 and thus higher levels of cortical F-actin and enhanced cell-cell adhesion. LGR5 ablation in colon cancer cells and crypt stem cells resulted in loss of cortical F-actin, reduced cell-cell adhesion, and disrupted localization of adhesion-associated proteins. No evidence of LGR5 coupling to any of the four major subtypes of heterotrimeric G proteins was found. These findings suggest that LGR5 primarily functions via the IQGAP1-Rac1 pathway to strengthen cell-cell adhesion in normal adult crypt stem cells and colon cancer cells.
[Mh] Termos MeSH primário: Adesão Celular
Neoplasias do Colo/patologia
Receptores Acoplados a Proteínas-G/metabolismo
Células-Tronco/citologia
Proteínas rac1 de Ligação ao GTP/metabolismo
Proteínas Ativadoras de ras GTPase/metabolismo
[Mh] Termos MeSH secundário: Animais
Células CHO
Células Cultivadas
Neoplasias do Colo/metabolismo
Cricetulus
Células HEK293
Seres Humanos
Células-Tronco/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (IQ motif containing GTPase activating protein 1); 0 (LGR5 protein, human); 0 (RAC1 protein, human); 0 (Receptors, G-Protein-Coupled); 0 (ras GTPase-Activating Proteins); EC 3.6.5.2 (rac1 GTP-Binding Protein)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170929
[Lr] Data última revisão:
170929
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170726
[St] Status:MEDLINE
[do] DOI:10.1074/jbc.M117.786798


  10 / 1510 MEDLINE  
              first record previous record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28720574
[Au] Autor:Jin X; Pan Y; Wang L; Ma T; Zhang L; Tang AH; Billadeau DD; Wu H; Huang H
[Ad] Endereço:Department of Digestive Surgical Oncology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
[Ti] Título:Fructose-1,6-bisphosphatase Inhibits ERK Activation and Bypasses Gemcitabine Resistance in Pancreatic Cancer by Blocking IQGAP1-MAPK Interaction.
[So] Source:Cancer Res;77(16):4328-4341, 2017 Aug 15.
[Is] ISSN:1538-7445
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Dysregulation of the MAPK pathway correlates with progression of pancreatic ductal adenocarcinoma (PDAC) progression. IQ motif containing GTPase-activating protein 1 (IQGAP1) is a MAPK scaffold that directly regulates the activation of RAF, MEK, and ERK. Fructose-1,6-bisphosphatase (FBP1), a key enzyme in gluconeogenesis, is transcriptionally downregulated in various cancers, including PDAC. Here, we demonstrate that FBP1 acts as a negative modulator of the IQGAP1-MAPK signaling axis in PDAC cells. FBP1 binding to the WW domain of IQGAP1 impeded IQGAP1-dependent ERK1/2 phosphorylation (pERK1/2) in a manner independent of FBP1 enzymatic activity. Conversely, decreased FBP1 expression induced pERK1/2 levels in PDAC cell lines and correlated with increased pERK1/2 levels in patient specimens. Treatment with gemcitabine caused undesirable activation of ERK1/2 in PDAC cells, but cotreatment with the FBP1-derived small peptide inhibitor FBP1 E4 overcame gemcitabine-induced ERK activation, thereby increasing the anticancer efficacy of gemcitabine in PDAC. These findings identify a primary mechanism of resistance of PDAC to standard therapy and suggest that the FBP1-IQGAP1-ERK1/2 signaling axis can be targeted for effective treatment of PDAC. .
[Mh] Termos MeSH primário: Antimetabólitos Antineoplásicos/farmacologia
Carcinoma Ductal Pancreático/tratamento farmacológico
Carcinoma Ductal Pancreático/genética
Desoxicitidina/análogos & derivados
Frutose-Bifosfatase/metabolismo
Sistema de Sinalização das MAP Quinases/efeitos dos fármacos
Neoplasias Pancreáticas/tratamento farmacológico
Neoplasias Pancreáticas/genética
Proteínas Ativadoras de ras GTPase/antagonistas & inibidores
[Mh] Termos MeSH secundário: Linhagem Celular Tumoral
Desoxicitidina/farmacologia
Resistência a Medicamentos Antineoplásicos
Frutose-Bifosfatase/genética
Seres Humanos
Neoplasias Pancreáticas/metabolismo
Transdução de Sinais
Transfecção
Proteínas Ativadoras de ras GTPase/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antimetabolites, Antineoplastic); 0 (IQ motif containing GTPase activating protein 1); 0 (ras GTPase-Activating Proteins); 0W860991D6 (Deoxycytidine); B76N6SBZ8R (gemcitabine); EC 3.1.3.11 (Fructose-Bisphosphatase)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170929
[Lr] Data última revisão:
170929
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170720
[St] Status:MEDLINE
[do] DOI:10.1158/0008-5472.CAN-16-3143



página 1 de 151 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