Base de dados : MEDLINE
Pesquisa : D12.776.157.725.813.250 [Categoria DeCS]
Referências encontradas : 79 [refinar]
Mostrando: 1 .. 10   no formato [Detalhado]

página 1 de 8 ir para página                    

  1 / 79 MEDLINE  
              next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28031331
[Au] Autor:Schultz AS; Preussner M; Bunse M; Karni R; Heyd F
[Ad] Endereço:Freie Universität Berlin, Institute of Chemistry and Biochemistry, Berlin, Germany.
[Ti] Título:Activation-Dependent TRAF3 Exon 8 Alternative Splicing Is Controlled by CELF2 and hnRNP C Binding to an Upstream Intronic Element.
[So] Source:Mol Cell Biol;37(7), 2017 Apr 01.
[Is] ISSN:1098-5549
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Cell-type-specific and inducible alternative splicing has a fundamental impact on regulating gene expression and cellular function in a variety of settings, including activation and differentiation. We have recently shown that activation-induced skipping of TRAF3 exon 8 activates noncanonical NF-κB signaling upon T cell stimulation, but the regulatory basis for this splicing event remains unknown. Here we identify - and -regulatory elements rendering this splicing switch activation dependent and cell type specific. The -acting element is located 340 to 440 nucleotides upstream of the regulated exon and acts in a distance-dependent manner, since altering the location reduces its activity. A small interfering RNA screen, followed by cross-link immunoprecipitation and mutational analyses, identified CELF2 and hnRNP C as -acting factors that directly bind the regulatory sequence and together mediate increased exon skipping in activated T cells. CELF2 expression levels correlate with TRAF3 exon skipping in several model systems, suggesting that CELF2 is the decisive factor, with hnRNP C being necessary but not sufficient. These data suggest an interplay between CELF2 and hnRNP C as the mechanistic basis for activation-dependent alternative splicing of TRAF3 exon 8 and additional exons and uncover an intronic splicing silencer whose full activity depends on the precise location more than 300 nucleotides upstream of the regulated exon.
[Mh] Termos MeSH primário: Processamento Alternativo/genética
Proteínas CELF/metabolismo
Éxons/genética
Ribonucleoproteínas Nucleares Heterogêneas Grupo C/metabolismo
Íntrons/genética
Ativação Linfocitária/genética
Proteínas do Tecido Nervoso/metabolismo
Fator 3 Associado a Receptor de TNF/genética
[Mh] Termos MeSH secundário: Sítios de Ligação
Células HEK293
Seres Humanos
Poli U/metabolismo
Ligação Proteica/genética
RNA Interferente Pequeno/metabolismo
Elementos Silenciadores Transcricionais/genética
Linfócitos T/imunologia
Fator 3 Associado a Receptor de TNF/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (CELF Proteins); 0 (CELF2 protein, human); 0 (Heterogeneous-Nuclear Ribonucleoprotein Group C); 0 (Nerve Tissue Proteins); 0 (RNA, Small Interfering); 0 (TNF Receptor-Associated Factor 3); 27416-86-0 (Poly U)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170917
[Lr] Data última revisão:
170917
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161230
[St] Status:MEDLINE


  2 / 79 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:27300488
[Au] Autor:Shetty M; Srikanth A; Kadandale J; Hegde S
[Ad] Endereço:Department of Medical Genetics, Manipal Hospital, Bangalore, India.
[Ti] Título:Pre- and Postnatal Diagnosis of 10p14 Deletion and 22q11.2 Deletion Syndrome and Significance of Non-Cardiac Markers.
[So] Source:Cytogenet Genome Res;148(4):249-55, 2016.
[Is] ISSN:1424-859X
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:Congenital heart defect (CHD) is the most common form of birth defects. There is a high association between increased nuchal translucency and CHD in fetuses, and CHD in the antenatal period has a high incidence of 22q11.2 deletion syndrome (22q11.2DS). Apart from 22q11.2DS, the BRUNOL3 gene at 10p14 is also associated with DiGeorge-like features. We studied a total of 110 pre- and postnatal CHD cases with FISH probes. 22q11.2DS was detected in 5 cases and 10p14 deletion in 1 case. Antenatally diagnosed cases of CHD should be investigated by karyotyping and 22q11.2DS testing. Cases with increased nuchal translucency, intrauterine growth retardation, and other non-cardiac malformations because of 22q11.2DS should be screened carefully for thymus dysgenesis. It is also advisable to screen patients referred for 22q11.2DS for a 10p14 deletion, therefore enabling appropriate parental counseling.
[Mh] Termos MeSH primário: Deleção Cromossômica
Cromossomos Humanos Par 10/genética
Cromossomos Humanos Par 22/genética
Síndrome de DiGeorge/genética
[Mh] Termos MeSH secundário: Anormalidades Múltiplas/genética
Biomarcadores
Proteínas CELF/genética
Feminino
Seres Humanos
Hibridização in Situ Fluorescente
Lactente
Cariótipo
Proteínas do Tecido Nervoso/genética
Diagnóstico Pré-Natal
Adulto Jovem
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers); 0 (CELF Proteins); 0 (CELF2 protein, human); 0 (Nerve Tissue Proteins)
[Em] Mês de entrada:1701
[Cu] Atualização por classe:170119
[Lr] Data última revisão:
170119
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160615
[St] Status:MEDLINE
[do] DOI:10.1159/000446162


  3 / 79 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
PubMed Central Texto completo
Texto completo
[PMID]:27253061
[Au] Autor:Chen L; Liu Z; Zhou B; Wei C; Zhou Y; Rosenfeld MG; Fu XD; Chisholm AD; Jin Y
[Ad] Endereço:Section of Neurobiology, University of California, San Diego, Division of Biological Sciences, San Diego, United States.
[Ti] Título:CELF RNA binding proteins promote axon regeneration in C. elegans and mammals through alternative splicing of Syntaxins.
[So] Source:Elife;5, 2016 Jun 02.
[Is] ISSN:2050-084X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Axon injury triggers dramatic changes in gene expression. While transcriptional regulation of injury-induced gene expression is widely studied, less is known about the roles of RNA binding proteins (RBPs) in post-transcriptional regulation during axon regeneration. In C. elegans the CELF (CUGBP and Etr-3 Like Factor) family RBP UNC-75 is required for axon regeneration. Using crosslinking immunoprecipitation coupled with deep sequencing (CLIP-seq) we identify a set of genes involved in synaptic transmission as mRNA targets of UNC-75. In particular, we show that UNC-75 regulates alternative splicing of two mRNA isoforms of the SNARE Syntaxin/unc-64. In C. elegans mutants lacking unc-75 or its targets, regenerating axons form growth cones, yet are deficient in extension. Extending these findings to mammalian axon regeneration, we show that mouse Celf2 expression is upregulated after peripheral nerve injury and that Celf2 mutant mice are defective in axon regeneration. Further, mRNAs for several Syntaxins show CELF2 dependent regulation. Our data delineate a post-transcriptional regulatory pathway with a conserved role in regenerative axon extension.
[Mh] Termos MeSH primário: Processamento Alternativo/genética
Axônios/fisiologia
Proteínas CELF/metabolismo
Caenorhabditis elegans/fisiologia
Proteínas Qa-SNARE/genética
[Mh] Termos MeSH secundário: Animais
Proteínas CELF/genética
Caenorhabditis elegans/genética
Proteínas de Caenorhabditis elegans/metabolismo
Regulação da Expressão Gênica
Locomoção
Camundongos
Camundongos Knockout
Mutação
Traumatismos dos Nervos Periféricos/metabolismo
Traumatismos dos Nervos Periféricos/patologia
Isoformas de Proteínas
Proteínas Qa-SNARE/metabolismo
Proteínas de Ligação a RNA/metabolismo
Regeneração
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (CELF Proteins); 0 (Caenorhabditis elegans Proteins); 0 (Celf2 protein, mouse); 0 (Protein Isoforms); 0 (Qa-SNARE Proteins); 0 (RNA-Binding Proteins); 0 (UNC-75 protein, C elegans)
[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:160603
[St] Status:MEDLINE


  4 / 79 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:27137075
[Au] Autor:Okuda J; Takeuchi Y; Yasuda M; Nakai T
[Ad] Endereço:Graduate School of Biosphere Science, Hiroshima University, Higashi-Hiroshima 739-8528, Japan.
[Ti] Título:ORF13 in the Type III secretion system gene cluster of Edwardsiella tarda binds to the mammalian factor Cugbp2.
[So] Source:Dis Aquat Organ;119(2):173-7, 2016 May 03.
[Is] ISSN:0177-5103
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:The Type III secretion system (TTSS) is essential for the intracellular replication of Edwardsiella tarda in phagocytes of fish and mammals, and a hypothetical gene (orf13) located in the TTSS gene cluster is required for intracellular replication and virulence of E. tarda. Here, we show that under TTSS-inducing conditions, the protein ORF13 was secreted into culture supernatant. Then, using a yeast 2-hybrid screen, we show that the mammalian factor Cugbp2, which regulates apoptosis in breast cancer cells, directly interacts with ORF13. A pull-down assay revealed that ORF13 binds to the C-terminal region of Cugbp2. Our results suggest that ORF13 may facilitate E. tarda replication in phagocytes by binding to Cugbp2.
[Mh] Termos MeSH primário: Proteínas de Bactérias/metabolismo
Edwardsiella tarda/metabolismo
Proteínas de Ligação a RNA/metabolismo
Sistemas de Secreção Tipo III/metabolismo
[Mh] Termos MeSH secundário: Animais
Proteínas de Bactérias/genética
Proteínas CELF/genética
Proteínas CELF/metabolismo
Edwardsiella tarda/genética
Infecções por Enterobacteriaceae/microbiologia
Infecções por Enterobacteriaceae/veterinária
Doenças dos Peixes/microbiologia
Linguado
Regulação Bacteriana da Expressão Gênica
Mamíferos
Camundongos
Técnicas do Sistema de Duplo-Híbrido
Sistemas de Secreção Tipo III/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Bacterial Proteins); 0 (CELF Proteins); 0 (Celf2 protein, mouse); 0 (RNA-Binding Proteins); 0 (Type III Secretion Systems)
[Em] Mês de entrada:1608
[Cu] Atualização por classe:160504
[Lr] Data última revisão:
160504
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160504
[St] Status:MEDLINE
[do] DOI:10.3354/dao02987


  5 / 79 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
PubMed Central Texto completo
Texto completo
[PMID]:27096301
[Au] Autor:Ajith S; Gazzara MR; Cole BS; Shankarling G; Martinez NM; Mallory MJ; Lynch KW
[Ad] Endereço:a Department of Biochemistry and Biophysics , University of Pennsylvania Perelman School of Medicine , Philadelphia , PA , USA.
[Ti] Título:Position-dependent activity of CELF2 in the regulation of splicing and implications for signal-responsive regulation in T cells.
[So] Source:RNA Biol;13(6):569-81, 2016 Jun 02.
[Is] ISSN:1555-8584
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:CELF2 is an RNA binding protein that has been implicated in developmental and signal-dependent splicing in the heart, brain and T cells. In the heart, CELF2 expression decreases during development, while in T cells CELF2 expression increases both during development and in response to antigen-induced signaling events. Although hundreds of CELF2-responsive splicing events have been identified in both heart and T cells, the way in which CELF2 functions has not been broadly investigated. Here we use CLIP-Seq to identified physical targets of CELF2 in a cultured human T cell line. By comparing the results with known functional targets of CELF2 splicing regulation from the same cell line we demonstrate a generalizable position-dependence of CELF2 activity that is consistent with previous mechanistic studies of individual CELF2 target genes in heart and brain. Strikingly, this general position-dependence is sufficient to explain the bi-directional activity of CELF2 on 2 T cell targets recently reported. Therefore, we propose that the location of CELF2 binding around an exon is a primary predictor of CELF2 function in a broad range of cellular contexts.
[Mh] Termos MeSH primário: Proteínas CELF/metabolismo
Proteínas do Tecido Nervoso/metabolismo
RNA/metabolismo
Análise de Sequência de RNA/métodos
Linfócitos T/metabolismo
[Mh] Termos MeSH secundário: Processamento Alternativo
Encéfalo/metabolismo
Células Cultivadas
Éxons
Regulação da Expressão Gênica no Desenvolvimento
Seres Humanos
Células Jurkat
Miocárdio/metabolismo
Processamento de RNA
Transdução de Sinais
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (CELF Proteins); 0 (CELF2 protein, human); 0 (Nerve Tissue Proteins); 63231-63-0 (RNA)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171011
[Lr] Data última revisão:
171011
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160421
[St] Status:MEDLINE
[do] DOI:10.1080/15476286.2016.1176663


  6 / 79 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Registro de Ensaios Clínicos
Texto completo
[PMID]:26811534
[Au] Autor:Wang X; Sun CL; Quiñones-Lombraña A; Singh P; Landier W; Hageman L; Mather M; Rotter JI; Taylor KD; Chen YD; Armenian SH; Winick N; Ginsberg JP; Neglia JP; Oeffinger KC; Castellino SM; Dreyer ZE; Hudson MM; Robison LL; Blanco JG; Bhatia S
[Ad] Endereço:Xuexia Wang, University of Wisconsin-Milwaukee, Milwaukee, WI; Can-Lan Sun, Molly Mather, Saro H. Armenian, City of Hope, Duarte; Jerome I. Rotter, Kent D. Taylor, Yii-Der Ida Chen, Los Angeles Biomedical Research Institute at Harbor-University of California, Los Angeles, Torrance, CA; Adolfo Quiñon
[Ti] Título:CELF4 Variant and Anthracycline-Related Cardiomyopathy: A Children's Oncology Group Genome-Wide Association Study.
[So] Source:J Clin Oncol;34(8):863-70, 2016 Mar 10.
[Is] ISSN:1527-7755
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:PURPOSE: Interindividual variability in the dose-dependent association between anthracyclines and cardiomyopathy suggests that genetic susceptibility could play a role. The current study uses an agnostic approach to identify genetic variants that could modify cardiomyopathy risk. METHODS: A genome-wide association study was conducted in childhood cancer survivors with and without cardiomyopathy (cases and controls, respectively). Single-nucleotide polymorphisms (SNPs) that surpassed a prespecified threshold for statistical significance were independently replicated. The possible mechanistic significance of validated SNP(s) was sought by using healthy heart samples. RESULTS: No SNP was marginally associated with cardiomyopathy. However, SNP rs1786814 on the CELF4 gene passed the significance cutoff for gene-environment interaction (Pge = 1.14 × 10(-5)). Multivariable analyses adjusted for age at cancer diagnosis, sex, anthracycline dose, and chest radiation revealed that, among patients with the A allele, cardiomyopathy was infrequent and not dose related. However, among those exposed to greater than 300 mg/m(2) of anthracyclines, the rs1786814 GG genotype conferred a 10.2-fold (95% CI, 3.8- to 27.3-fold; P < .001) increased risk of cardiomyopathy compared with those who had GA/AA genotypes and anthracycline exposure of 300 mg/m(2) or less. This gene-environment interaction was successfully replicated in an independent set of anthracycline-related cardiomyopathy. CUG-BP and ETR-3-like factor proteins control developmentally regulated splicing of TNNT2, the gene that encodes for cardiac troponin T (cTnT), a biomarker of myocardial injury. Coexistence of more than one cTnT variant results in a temporally split myofilament response to calcium, which causes decreased contractility. Analysis of TNNT2 splicing variants in healthy human hearts suggested an association between the rs1786814 GG genotype and coexistence of more than one TNNT2 splicing variant (90.5% GG v 41.7% GA/AA; P = .005). CONCLUSION: We report a modifying effect of a polymorphism of CELF4 (rs1786814) on the dose-dependent association between anthracyclines and cardiomyopathy, which possibly occurs through a pathway that involves the expression of abnormally spliced TNNT2 variants.
[Mh] Termos MeSH primário: Antraciclinas/efeitos adversos
Proteínas CELF/genética
Cardiomiopatias/induzido quimicamente
Cardiomiopatias/genética
[Mh] Termos MeSH secundário: Adolescente
Adulto
Cardiomiopatias/metabolismo
Estudos de Casos e Controles
Criança
Pré-Escolar
Relação Dose-Resposta a Droga
Feminino
Estudo de Associação Genômica Ampla
Seres Humanos
Lactente
Recém-Nascido
Masculino
Polimorfismo de Nucleotídeo Único
Isoformas de Proteínas
Troponina T/biossíntese
Troponina T/genética
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Anthracyclines); 0 (CELF Proteins); 0 (CELF4 protein, human); 0 (Protein Isoforms); 0 (TNNT2 protein, human); 0 (Troponin T)
[Em] Mês de entrada:1607
[Cu] Atualização por classe:170224
[Lr] Data última revisão:
170224
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160127
[Cl] Clinical Trial:ClinicalTrial
[St] Status:MEDLINE
[do] DOI:10.1200/JCO.2015.63.4550


  7 / 79 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
PubMed Central Texto completo
Texto completo
[PMID]:26796035
[Au] Autor:Martone J; Briganti F; Legnini I; Morlando M; Picillo E; Sthandier O; Politano L; Bozzoni I
[Ad] Endereço:Department of Biology and Biotechnology Charles Darwin, Sapienza University of Rome, P.le A. Moro 5, Rome 00185, Italy.
[Ti] Título:The lack of the Celf2a splicing factor converts a Duchenne genotype into a Becker phenotype.
[So] Source:Nat Commun;7:10488, 2016 Jan 22.
[Is] ISSN:2041-1723
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Substitutions, deletions and duplications in the dystrophin gene lead to either the severe Duchenne muscular dystrophy (DMD) or mild Becker muscular dystrophy depending on whether out-of-frame or in-frame transcripts are produced. We identified a DMD case (GSΔ44) where the correlation between genotype and phenotype is not respected, even if carrying a typical Duchenne mutation (exon 44 deletion) a Becker-like phenotype was observed. Here we report that in this patient, partial restoration of an in-frame transcript occurs by natural skipping of exon 45 and that this is due to the lack of Celf2a, a splicing factor that interacts with exon 45 in the dystrophin pre-mRNA. Several experiments are presented that demonstrate the central role of Celf2a in controlling exon 45 splicing; our data point to this factor as a potential target for the improvement of those DMD therapeutic treatments, which requires exon 45 skipping.
[Mh] Termos MeSH primário: Proteínas CELF/genética
Distrofia Muscular de Duchenne/genética
Proteínas do Tecido Nervoso/genética
[Mh] Termos MeSH secundário: Adolescente
Proteínas CELF/metabolismo
Distrofina/genética
Distrofina/metabolismo
Éxons
Genótipo
Seres Humanos
Masculino
Distrofia Muscular de Duchenne/metabolismo
Proteínas do Tecido Nervoso/metabolismo
Fenótipo
Processamento de RNA
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (CELF Proteins); 0 (CELF2 protein, human); 0 (Dystrophin); 0 (Nerve Tissue Proteins)
[Em] Mês de entrada:1606
[Cu] Atualização por classe:170922
[Lr] Data última revisão:
170922
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160123
[St] Status:MEDLINE
[do] DOI:10.1038/ncomms10488


  8 / 79 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:26691217
[Au] Autor:Jakstaite A; Maziukiene A; Silkuniene G; Kmieliute K; Dauksa A; Paskauskas S; Gulbinas A; Dambrauskas Z
[Ad] Endereço:Institute for Digestive System Research, Lithuanian University of Health Sciences, Eiveniu str. 4, Kaunas, 50161, Lithuania. aldona.jakstaite@gmail.com.
[Ti] Título:Upregulation of cugbp2 increases response of pancreatic cancer cells to chemotherapy.
[So] Source:Langenbecks Arch Surg;401(1):99-111, 2016 Feb.
[Is] ISSN:1435-2451
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:PURPOSE: Altered expression and/or function of ribosomal RNA (rRNA)-binding proteins CUGBP2/CELF2 might influence post-transcriptional regulation of the HO-1- and COX-2-mediated cytoprotective pathways and represents an important therapeutic target. The aim of this study was to assess the effects of CUGBP2-mediated post-transcriptional regulation of COX-2 and HO-1 in pancreatic cancer cells in regard of response to gemcitabine (GEM) treatment. METHODS: Expression of CUGBP2, COX-2, and HO-1 was evaluated using qRT-PCR and Western blot methods. Cell viability after treatment with GEM and/or curcumin and siCUGBP2 was evaluated using MTT and crystal violet tests. RNA immunoprecipitation analysis was used to confirm COX-2 and HO-1 post-transcriptional regulation by CUGBP2 protein. RESULTS: CUGBP2 expression at the messenger RNA (mRNA) level was 2.2-fold lower (p = 0.007), but HO-1 and COX-2 expression was increased 6.9- (p = 0.023) and 2.3- (p = 0.046) fold in pancreatic cancer tissues. The median survival of patients with low CUGBP2 expression from the lowest tercile was 13.8 months. The median survival of patients in terciles of middle and high CUGBP2 expression levels was 21.9 month (p = 0.123). Induction of CUGBP2 expression by curcumin resulted in the downregulation of HO-1 and COX-2 and strongly sensitized tumor cells to GEM treatment. However, CUGBP2 silencing upregulated HO-1 and COX-2 protein expression and had a high effect on cells viability. CONCLUSION: Decreased activity of CUGBP2 could be associated with high chemoresistance and early dissemination of pancreatic cancer through the HO-1- and COX-2-mediated cytoprotective and carcinogenesis pathways. Curcumin significantly increased the effectiveness of GEM treatment in vitro via the CUGBP2-mediated post-transcriptional regulation pathway.
[Mh] Termos MeSH primário: Antineoplásicos/uso terapêutico
Proteínas CELF/metabolismo
Resistência a Medicamentos Antineoplásicos/genética
Proteínas do Tecido Nervoso/metabolismo
Neoplasias Pancreáticas/tratamento farmacológico
Neoplasias Pancreáticas/metabolismo
[Mh] Termos MeSH secundário: Idoso
Ciclo-Oxigenase 2/metabolismo
Feminino
Heme Oxigenase-1/metabolismo
Seres Humanos
Masculino
Meia-Idade
Neoplasias Pancreáticas/genética
RNA Mensageiro/genética
RNA Mensageiro/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (CELF Proteins); 0 (CELF2 protein, human); 0 (Nerve Tissue Proteins); 0 (RNA, Messenger); EC 1.14.14.18 (Heme Oxygenase-1); EC 1.14.99.1 (Cyclooxygenase 2)
[Em] Mês de entrada:1701
[Cu] Atualização por classe:171005
[Lr] Data última revisão:
171005
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:151223
[St] Status:MEDLINE
[do] DOI:10.1007/s00423-015-1364-1


  9 / 79 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:25682262
[Au] Autor:Maloney SE; Khangura E; Dougherty JD
[Ad] Endereço:Department of Genetics, Washington University School of Medicine, Campus Box 8232, 4566 Scott Ave., St. Louis, MO, 63110, USA.
[Ti] Título:The RNA-binding protein Celf6 is highly expressed in diencephalic nuclei and neuromodulatory cell populations of the mouse brain.
[So] Source:Brain Struct Funct;221(4):1809-31, 2016 May.
[Is] ISSN:1863-2661
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:The gene CUG-BP, Elav-like factor 6 (CELF6) appears to be important for proper functioning of neurocircuitry responsible for behavioral output. We previously discovered that polymorphisms in or near CELF6 may be associated with autism spectrum disorder (ASD) in humans and that the deletion of this gene in mice results in a partial ASD-like phenotype. Here, to begin to understand which circuits might mediate these behavioral disruptions, we sought to establish in what structures, with what abundance, and at which ages Celf6 protein is present in the mouse brain. Using both a knockout-validated antibody to Celf6 and a novel transgenic mouse line, we characterized Celf6 expression in the mouse brain across development. Celf6 gene products were present early in neurodevelopment and in adulthood. The greatest protein expression was observed in distinct nuclei of the diencephalon and neuromodulatory cell populations of the midbrain and hindbrain, with clear expression in dopaminergic, noradrenergic, histaminergic, serotonergic and cholinergic populations, and a variety of presumptive peptidergic cells of the hypothalamus. These results suggest that disruption of Celf6 expression in hypothalamic nuclei may impact a variety of behaviors downstream of neuropeptide activity, while disruption in neuromodulatory transmitter expressing areas such as the ventral tegmental area, substantia nigra, raphe nuclei and locus coeruleus may have far-reaching influences on overall brain activity.
[Mh] Termos MeSH primário: Encéfalo/crescimento & desenvolvimento
Encéfalo/metabolismo
Proteínas CELF/metabolismo
Diencéfalo/crescimento & desenvolvimento
Diencéfalo/metabolismo
Neurônios/metabolismo
[Mh] Termos MeSH secundário: Neurônios Adrenérgicos/metabolismo
Animais
Proteínas CELF/genética
Neurônios Colinérgicos/metabolismo
Neurônios Dopaminérgicos/metabolismo
Hipotálamo/metabolismo
Mesencéfalo/crescimento & desenvolvimento
Mesencéfalo/metabolismo
Camundongos
Camundongos Endogâmicos C57BL
Camundongos Knockout
Rombencéfalo/crescimento & desenvolvimento
Rombencéfalo/metabolismo
Neurônios Serotoninérgicos/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (CELF Proteins); 0 (Celf6 protein, mouse)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171003
[Lr] Data última revisão:
171003
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150216
[St] Status:MEDLINE
[do] DOI:10.1007/s00429-015-1005-z


  10 / 79 MEDLINE  
              first record previous record
seleciona
para imprimir
Fotocópia
PubMed Central Texto completo
Texto completo
[PMID]:26443849
[Au] Autor:Martinez NM; Agosto L; Qiu J; Mallory MJ; Gazzara MR; Barash Y; Fu XD; Lynch KW
[Ad] Endereço:Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA; Biochemistry and Molecular Biophysics Graduate Group, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA;
[Ti] Título:Widespread JNK-dependent alternative splicing induces a positive feedback loop through CELF2-mediated regulation of MKK7 during T-cell activation.
[So] Source:Genes Dev;29(19):2054-66, 2015 Oct 01.
[Is] ISSN:1549-5477
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Alternative splicing is prevalent among genes encoding signaling molecules; however, the functional consequence of differential isoform expression remains largely unknown. Here we demonstrate that, in response to T-cell activation, the Jun kinase (JNK) kinase MAP kinase kinase 7 (MKK7) is alternatively spliced to favor an isoform that lacks exon 2. This isoform restores a JNK-docking site within MKK7 that is disrupted in the larger isoform. Consistently, we show that skipping of MKK7 exon 2 enhances JNK pathway activity, as indicated by c-Jun phosphorylation and up-regulation of TNF-α. Moreover, this splicing event is itself dependent on JNK signaling. Thus, MKK7 alternative splicing represents a positive feedback loop through which JNK promotes its own signaling. We further show that repression of MKK7 exon 2 is dependent on the presence of flanking sequences and the JNK-induced expression of the RNA-binding protein CELF2, which binds to these regulatory elements. Finally, we found that ∼25% of T-cell receptor-mediated alternative splicing events are dependent on JNK signaling. Strikingly, these JNK-dependent events are also significantly enriched for responsiveness to CELF2. Together, our data demonstrate a widespread role for the JNK-CELF2 axis in controlling splicing during T-cell activation, including a specific role in propagating JNK signaling.
[Mh] Termos MeSH primário: Processamento Alternativo/genética
Proteínas CELF/metabolismo
Regulação da Expressão Gênica
Proteínas Quinases JNK Ativadas por Mitógeno/genética
Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo
MAP Quinase Quinase 7/genética
Proteínas do Tecido Nervoso/metabolismo
Linfócitos T/metabolismo
[Mh] Termos MeSH secundário: Linfócitos T CD4-Positivos/citologia
Linfócitos T CD4-Positivos/metabolismo
Retroalimentação Fisiológica/fisiologia
Seres Humanos
Células Jurkat
MAP Quinase Quinase 7/metabolismo
Estabilidade de RNA/genética
Transdução de Sinais/genética
Linfócitos T/citologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (CELF Proteins); 0 (CELF2 protein, human); 0 (Nerve Tissue Proteins); EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases); EC 2.7.12.2 (MAP Kinase Kinase 7)
[Em] Mês de entrada:1601
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:151008
[St] Status:MEDLINE
[do] DOI:10.1101/gad.267245.115



página 1 de 8 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