Página 1 dos resultados de 17925 itens digitais encontrados em 0.012 segundos

Contact sensitizer nickel sulfate activates the transcription factors NF-kB and AP-1 and increases the expression of nitric oxide synthase in a skin dendritic cell line

Cruz, M. Teresa; Gonçalo, Margarida; Figueiredo, Américo; Carvalho, Arsélio P.; Duarte, Carlos B.; Lopes, M. Celeste
Fonte: Blackwell Munksgaard Publicador: Blackwell Munksgaard
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
36.550828%
Nuclear factor kappa B (NF-kB) and activating protein-1 (AP-1) transcription factors are ubiquitously expressed signaling molecules known to regulate the transcription of a large number of genes involved in immune responses, namely the inducible isoform of nitric oxide synthase (iNOS). In this study, we demonstrate that a fetal skin-derived dendritic cell line (FSDC) produces nitric oxide (NO) in response to the contact sensitizer nickel sulfate (NiSO4) and increases the expression of the iNOS protein, as determined by immunofluorescence and Western blot analysis. The sensitizer NiSO4 increased cytoplasmic iNOS expression by 31.9+10.3% and nitrite production, as assayed by the Griess reaction, by 27.6+9.5%. Electrophoretic mobility shift assay (EMSA), showed that 30min of FSDC exposure to NiSO4 activates the transcription factor NF-kB by 58.2+7.0% and 2 h of FSDC exposure to NiSO4 activates the transcription factor AP-1 by 26.0+1.4%. Together, these results indicate that NiSO4 activates the NF-kB and AP-1 pathways and induces iNOS expression in skin dendritic cells.

Excitotoxicity mediated by Ca2+-permeable GluR4-containing AMPA receptors involves the AP-1 transcription factor

Santos, A. E.; Duarte, C. B.; Iizuka, M.; Barsoumian, E. L.; Ham, J.; Lopes, M. C.; Carvalho, A. P.; Carvalho, A. L.
Fonte: Nature Publishing Group Publicador: Nature Publishing Group
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
36.550828%
Cells preferentially expressing GluR4-containing alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptors are particularly sensitive to excitotoxicity mediated through non-N-methyl-D-aspartate receptors. However, the excitotoxic signalling pathways associated with GluR4-containing AMPA receptors are not known. In this work, we investigated the downstream signals coupled to excitotoxicity mediated by Ca2+-permeable GluR4-containing AMPA receptors, using a HEK 293 cell line constitutively expressing the GluR4flip subunit of AMPA receptors (HEK-GluR4). Glutamate stimulation of GluR4-containing AMPA receptors decreased cell viability, in a calcium-dependent manner, when the receptor desensitisation was prevented with cyclothiazide. The excitotoxic stimulation mediated through GluR4-containing AMPA receptors increased activator protein-1 (AP-1) DNA-binding activity. Inhibition of the AP-1 activity by overexpression of a c-Jun dominant-negative form protected HEK-GluR4 cells against excitotoxic damage. Taken together, the results indicate that overactivation of Ca2+-permeable GluR4-containing AMPA receptors is coupled to a death pathway mediated, at least in part, by the AP-1 transcription factor

Expression of transcription factors NF-kappa B and AP-1 in nasal polyposis

VALERA, F. C. P.; QUEIROZ, R.; SCRIDELI, C.; TONE, L. G.; ANSELMO-LIMA, W. T.
Fonte: BLACKWELL PUBLISHING Publicador: BLACKWELL PUBLISHING
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
36.550828%
Background The treatment and prognosis of nasal polyposis (NP) may be influenced by transcription factors, but their expression is poorly understood. Objective To determine the expression of transcription factors [(nuclear factor-kappa B) NF-kappa B and (activator protein) AP-1], cytokines [IL-1 beta, TNF-alpha and (granulocytes and macrophage colony-stimulating factor) GM-CSF], growth factor (b-FGF), chemokine (eotaxin-2) and adhesion molecule (ICAM-1) in NP in comparison with nasal mucosa controls. Methods Cross-sectional study. Twenty biopsies of nasal polyps were compared with eight middle turbinate biopsies. p65, c-Fos, IL-1 beta, TNF-alpha, ICAM-1, b-FGF, eotaxin-2 and GM-CSF were analysed through RQ-PCR, and p65 and c-Fos were also analysed through Western blotting. Results NF-kappa B expression was increased in patients with NP when compared with control mucosa (P < 0.05), whereas AP-1 expression did not differ significantly between groups. Expressions of IL-1 beta, eotaxin-2 and b-FGF were also increased in patients with NP compared with controls (P < 0.05). Conclusions The transcription factor NF-kappa B is more expressed in NP than in control mucosa. This is important in NP because NF-kappa B can induce the transcription of cytokines...

"Determinação do perfil de expressão dos RNAs mensageiros da família das Smads e dos componentes do complexo AP-1 em carcinoma de célula escamosa de cabeça e pescoço" ; Smads and AP-1 messenger RNA expression pattern in Head and Neck Squamous Cell Carcinoma

Mangone, Flavia Regina Rotea
Fonte: Biblioteca Digitais de Teses e Dissertações da USP Publicador: Biblioteca Digitais de Teses e Dissertações da USP
Tipo: Tese de Doutorado Formato: application/pdf
Publicado em 28/03/2005 Português
Relevância na Pesquisa
36.602522%
A expressão de Smads e de membros da família AP1/ jun-fos podem refletir alterações da via de TGFb, uma via importante para o câncer epidermóide de cabeça e pescoço (HNSCC). Encontramos expressão aumentada dos mRNAs das Smads1-8 em HNSCC em comparação com tecido normal adjacente, por RPA. Além disso, as curvas de sobrevida de Kaplan Meier e a análise multivariada mostraram que a Smad6+ parece ser um fator determinante de bom prognóstico em HNSCC. Quanto a família AP-1, mensurado por Northern blot, somente Fra-1 mostrou-se aumentado no tumor e associado à presença de linfonodos comprometidos. Nossos dados sugerem que a positividade de Smad6 possa ser marcador de bom prognóstico em HNSCC ; Smad and AP1 messenger RNA expression may underlie disruptions affecting TGFb signaling in head and neck squamous cell carcinoma (HNSCC). Analysis of Smads1-8 mRNA expression by RPA has shown Smad expression is globally increased in tumor as compared to adjacent normal tissue. Kaplan Meier survival curves and multivariate analysis revealed that Smad6 positivity in tumor was an independent good prognostic factor in HNSCC. In relation to AP-1, as measured by Northern blot, only Fra-1 was overexpressed in tumor and directly related to the presence of lymph node involvement. Our data suggest that Smad6 may be a marker of good prognosis in HNSCC

Efeitos de ACTH, PMA e dcAMP na expressão de genes das famílias FOS e JUN do gene C-MYC e na atividade do fator de transcrição AP-1 em células adrenocorticais Y-1.; Effects of ACTH, PMA and dcAMP on fos, jun and c-myc gene expression and AP-1 transcription factor activity control in Y-1 adrenocortical cells

Lepique, Ana Paula
Fonte: Biblioteca Digitais de Teses e Dissertações da USP Publicador: Biblioteca Digitais de Teses e Dissertações da USP
Tipo: Dissertação de Mestrado Formato: application/pdf
Publicado em 04/11/1996 Português
Relevância na Pesquisa
36.672197%
As células Y-1 pertencem a uma linhagem clonal de células funcionais de córtex adrenal de camundongo, que respondem a ACTH. Em células Y-1, ACTH promove a esteroidogênese (função) e tem efeitos regulatórios complexos na transição G0→G1→S do ciclo celular. ACTH promove a transição G0→G1, mas inibe a transição G1→S. É possível que a regulação do ciclo celular por ACTH seja mediada pelo controle da expressão dos proto-oncogenes das famílias fos, jun e myc. Nosso laboratório mostrou, anteriormente, que ACTH induz a expressão dos genes fos e jun, mas inibe c-myc. O objetivo deste trabalho foi identificar pontos de controle na expressão dos genes fos, jun e myc e na atividade dos fatores de transcrição AP-1 (dímeros da proteínas Fos e Jun) por ACTH, derivados de cAMP (ativadores de PKA), PMA (ativador de PKC) e FCS (soro fetal bovino). ACTH, PMA e dcAMP aumentam a atividade de ligação de AP-1 a DNA, independentemente de síntese protéica. Ensaios de elongação de cadeia nascente de RNA (run off transcription) mostram que ACTH, PMA e FCS são fortes indutores de c-fos, c-jun e junB, enquanto dcAMP induz apenas c-fos e junB. Hibridizações Northern permitiram estimar a meia-vida dos mRNAs de c-fos e c-jun em 30 min...

Papel do fator de transcrição AP-1 na hipernocicepção neuropática em camundongos; Role of the AP-1 transcription factor in neuropathic hypernociception in mice.

Poloni, Rafael
Fonte: Biblioteca Digitais de Teses e Dissertações da USP Publicador: Biblioteca Digitais de Teses e Dissertações da USP
Tipo: Tese de Doutorado Formato: application/pdf
Publicado em 24/02/2014 Português
Relevância na Pesquisa
36.808787%
A dor neuropática pode ser causada por lesões e/ou disfunções no sistema somatossensorial. Nestes tipos de dores, alterações plásticas ao longo de todo o sistema sensorial nociceptivo estão associadas à cronificação do processo doloroso. A plasticidade observada pode ser resultante da indução e/ou repressão de genes, os quais geralmente são modulados por fatores de transcrição. Um dos principais fatores de transcrição até então conhecido é a proteína ativadora-1 (AP-1), que pode ser estruturalmente formado principalmente por proteínas das famílias Jun e Fos. Entretanto, na dor neuropática, a participação e o papel do AP-1 não estão bem elucidados. Dessa forma, a hipótese deste trabalho é que a ativação do AP-1 contribua para a indução e/ou manutenção da dor neuropática, através da ativação de células gliais e de proteinocinases ativadas por mitógenos (MAPK) e por indução da produção e liberação de mediadores pró-inflamatórios, bem como de metaloproteinases da matriz extracelular (MMP) na medula espinal. Esses fatores contribuem para sensibilização central causada pela SNI, facilitando a transmissão dolorosa. Assim, a inibição do AP-1 seria uma potencial estratégia terapêutica no tratamento da dor neuropática. Foi utilizado o modelo experimental de dor neuropática de lesão limitada do nervo isquiático (SNI...

Clonagem, expressão, purificação e caracterização estrutural da região AP-1 da oncoproteína Jun; Cloning, expression, purification and structural evaluation of the region AP-1 oncoprotein Jun

Silva, Flavio Sousa
Fonte: Biblioteca Digitais de Teses e Dissertações da USP Publicador: Biblioteca Digitais de Teses e Dissertações da USP
Tipo: Dissertação de Mestrado Formato: application/pdf
Publicado em 25/06/2014 Português
Relevância na Pesquisa
36.672197%
A proteína jun é um dos principais integrantes do complexo AP-1 e está envolvido nos processos inflamatórios, diferenciação, apoptose e migração celular. Esta proteína pode formar homodímeros e heterodímeros por meio da dimerização que ocorre pelo sítio de sequências de leucinas. Existem evidências de que a proteína jun pode ser inibida pela proteína RPL10 mediante a ligação destas proteínas, no mesmo sítio de sequências de leucinas no núcleo celular, parando a progressão de tumores. O objetivo deste trabalho foi expressar, isolar e caracterizar a região de ligação das sequências de leucinas (região AP-1), para estudos posteriores de ligação com a proteína RPL10. O cDNA para proteína jun foi amplificado por PCR e clonado nos vetores de expressão pET 26b(+), pET 28a-c(+) e p1813 e expressa em E.coli BL21 (DE3). A proteína expressa em vetor pET28_AP1 foi eficientemente purificada pela técnica de cromatografia de afinidade a íons metálicos, por possuir uma sequência (poli)histidina que facilitou a purificação, apresentando um excelente grau de pureza. A identidade da proteína foi confirmada através de análise feita por western blotting e dot blotting e também por analise por espectrometria de massas.; The jun protein is one of the main AP-1 complex members and is involved in the inflammatory process...

Aplicabilidade do programa de eficiência energética Eco.Ap

Santos, João Dinis Gomes dos
Fonte: Universidade de Lisboa Publicador: Universidade de Lisboa
Tipo: Dissertação de Mestrado
Publicado em //2012 Português
Relevância na Pesquisa
36.78886%
Tese de mestrado integrado em Engenharia da Energia e do Ambiente, apresentada à Universidade de Lisboa, através da Faculdade de Ciências, 2012; A eficiência energética é uma matéria que tem vindo a assumir maior relevância na sociedade, face aos compromissos internacionais no combate ao desperdício de energia e às alterações climáticas. É neste contexto que o Governo Português avança com o Programa de Eficiência Energética na Administração Pública (Eco.Ap), que tem como objectivos promover a eficiência energética na administração pública e desenvolver um novo mercado de serviços de energia, através da contratação de Empresas de Serviços Energéticos (ESE) e da promoção de Contratos de Desempenho Energético (CDE). Esta dissertação tem como objectivo principal analisar a aplicabilidade do programa Eco.Ap, através de uma avaliação energética realizada a um dos edifícios com potencialidades para ser abrangido neste programa e com base na análise crítica aos modelos do Caderno de Encargos e Programa de Procedimentos Tipo (versões colocadas para consulta pública em Março de 2012) propostos para o programa Eco.Ap. O edifício objecto de estudo encontra-se no Campus do Laboratório Nacional de Energia e Geologia (LNEG). O estudo incluiu a participação numa auditoria energética...

Caracterização de dois cDNAs homológos e uma AP endonuclease em cana-de-açúcar

Oliveira, Andrea de Lima
Fonte: Universidade Federal do Rio Grande do Norte; BR; UFRN; Programa de Pós-Graduação em Genética e Biologia Molecular; Genética e Biologia Molecular Publicador: Universidade Federal do Rio Grande do Norte; BR; UFRN; Programa de Pós-Graduação em Genética e Biologia Molecular; Genética e Biologia Molecular
Tipo: Dissertação Formato: application/pdf
Português
Relevância na Pesquisa
36.641606%
The genome of all organisms is subject to injuries that can be caused by endogenous and environmental factors. If these lesions are not corrected, it can be fixed generating a mutation which can be lethal to the organisms. In order to prevent this, there are different DNA repair mechanisms. These mechanisms are well known in bacteria, yeast, human, but not in plants. Two plant models Oriza sativa and Arabidopsis thaliana had the genome sequenced and due to this some DNA repair genes have been characterized. The aim of this work is to characterized two sugarcane cDNAs that had homology to AP endonuclease: scARP1 and scARP3. In silico has been done with these two sequences and other from plants. It has been observed domain conservation on these sequences, but the cystein at 65 position that is a characteristic from the redox domain in APE1 protein was not so conservated in plants. Phylogenetic relationship showed two branches, one branch with dicots and monocots sequence and the other branch with only monocots sequences. Another approach in order to characterized these two cDNAs was to construct overexpression cassettes (sense and antisense orientation) using the 35S promoter. After that, these cassettes were transferred to the binary vector pPZP211. Furthermore...

Distribui??o espacial de criadouros de Aedes (Stegomyia) aegypti Linnaeus 1762 (Diptera: Culicidae) em pontos georreferenciados de dois bairros da cidade de Macap?-AP: ?rea end?mica de dengue

CORR?A, Ana Paula Sales de Andrade
Fonte: Universidade Federal do Pará Publicador: Universidade Federal do Pará
Tipo: Dissertação de Mestrado
Português
Relevância na Pesquisa
36.602522%
O presente trabalho teve como objetivo estudar a distribui??o espacial dos criadouros de Aedes (Stegomyia) aegypti Linnaeus 1762 Diptera: Culicidae) em pontos georreferenciados de dois bairros da cidade de Macap?-AP. Os esp?cimes foram coletados em dois per?odos (seco e chuvoso) e analisados qualitativa e quantitativamente. Realizou-se mapeamento dos im?veis inspecionados, destacando-se aqueles com criadouros positivos para formas imaturas de A. aegypti, al?m de entrevistas com os residentes locais, a fim de se avaliar aspectos s?cio-econ?micos relacionados ? ocorr?ncia da esp?cie em quest?o. No bairro do Trem os dep?sitos m?veis, detiveram 21,90% das larvas coletadas no per?odo seco e 24,60% no per?odo chuvoso; dep?sitos fixos 22,38% no per?odo seco e 20,59% no per?odo chuvoso; e dep?sitos remov?veis 49,05% no per?odo seco e 48,93% no per?odo chuvoso. No Bairro Cidade Nova as fossas e dep?sitos de ?gua para consumo, detiveram 26,79% e 18,66% no per?odo seco respectivamente. No per?odo chuvoso, os dep?sitos de ?gua para consumo subiram para 34,16 %, as fossas se mantiveram inalteradas, sugerindo que esse ?ltimo seja considerado um recipiente preferencial para a desova do mosquito. Constatou-se que o abastecimento de ?gua encanada cobre 93% das resid?ncias do bairro do Trem...

Regulation of MAPK activation, AP-1 transcription factor expression and keratinocyte differentiation in wounded fetal skin

Gangnuss, S.; Cowin, A.; Daehn, I.; Hatzirodos, N.; Rothnagel, J.; Varelias, A.; Rayner, T.
Fonte: Blackwell Publishing Inc Publicador: Blackwell Publishing Inc
Tipo: Artigo de Revista Científica
Publicado em //2004 Português
Relevância na Pesquisa
36.602522%
Fetal epithelium retains the ability to re-epithelialize a wound in organotypic culture in a manner not dependent on the presence of underlying dermal substrata. This capacity is lost late in the third trimester of gestation or after embryonic day 17 (E(17)) in the rat such that embryonic day 19 (E(19)) wounds do not re-epithelialize. Moreover, wounds created in E(17) fetuses in utero heal in a regenerative, scar-free fashion. To investigate the molecular events regulating re-epithelialization in fetal skin, the wound-induced expression profile and tissue localization of activator protein 1 (AP-1) transcription factors c-Fos and c-Jun was characterised in E(17) and E(19) skin using organotypic fetal cultures. The involvement of mitogen-activated protein kinase (MAPK) signaling in mediating wound-induced transcription factor expression and wound re-epithelialization was assessed, with the effect of wounding on the expression of keratinocyte differentiation markers determined. Our results show that expression of AP-1 transcription factors was induced immediately by wounding and localized predominantly to the epidermis in E(17) and E(19) skin. c-fos and c-jun induction was transient in E(17) skin with MAPK-dependent c-fos expression necessary for the re-epithelialization of an excisional wound in organotypic culture. In E(19) skin...

Die Rolle von AP-2alpha bei der Melanomentstehung und Progression; The role of AP-2alpha in developement and progression of malignant melanoma

Grieb, Cornelia
Fonte: Universidade de Tubinga Publicador: Universidade de Tubinga
Tipo: Dissertação
Português
Relevância na Pesquisa
36.838186%
Der Transkriptionsfaktor AP-2alpha spielt eine entscheidende Rolle bei der Regulation der Expression von verschiedenen Genen, die für das Wachstum und die Progression des malignen Melanoms wichtig sind. Das Ziel der vorliegenden Arbeit bestand in der Untersuchung des Expressionsprofils von AP-2alpha in der Tumorprogression des malignen Melanoms. Die AP-2alpha-Expression wurde einerseits an Zelllinien analysiert, die von Melanozyten über melanozytäre Nävi, von Melanomen der radialen und vertikalen Wachstumsphase, von metastasierten Melanomen und einigen anderen Tumorzelllinien sowie von normalem Gewebe etabliert worden sind. Andererseits wurde die Expression von AP-2alpha auf verschiedenen Ebenen untersucht, dass bedeutet auf DNA-, RNA- und Proteinebene. Hierzu wurden die Methoden der PCR, des Northern Blottings, des Western Blottings und der Immunhistologie in Verbindung mit der konfokalen Laserscanningmikroskopie angewandt. In situ konnte mit Hilfe von Immunhistologie und konfokaler Laserscanningmikroskopie eine deutliche Herunterregulation der AP-2alpha Expression im Verlauf der Melanomprogression gezeigt werden. Dabei konnte eine Verschiebung der Lokalisation des AP-2alpha Proteins beobachtet werden. Während bei Nävuszellen und Primärmelanomen AP-2alpha vermehrt im Kern nachweisbar war (aktivierte Form)...

Insulin-like Growth Factor I (IGF-I), IGFBP-3 und Alkalische Phosphatase (AP) bei idiopathischem Wachstumshormonmangel (iGHD) und Neurosekretorischer Dysfunktion (NSD) vor und während der Therapie mit Wachstumshormon (GH); Insulin-like Growth Factor I (IGF-I), IGFBP-3 and Alkaline Phosphatase (AP) in children with idiopathic Growth Hormone Deficiency (iGHD) and Neurosecretoric Dysfunction (NSD) before and during therapy with human Growth Hormone (GH)

Rist, Roland
Fonte: Universität Tübingen Publicador: Universität Tübingen
Tipo: Dissertation; info:eu-repo/semantics/doctoralThesis
Português
Relevância na Pesquisa
36.716987%
Es wurden 116 überwiegend präpubertäre Kinder über einen Zeitraum von einem bzw. vier Jahren untersucht, die an der Universitäts-Kinderklinik Tübingen wegen idiopathischem Wachstumshormonmangel (iGHD) oder wegen Neurosekretorischer Dysfunktion (NSD) mit ca. 0,6 IU rekombinantem Wachstumshormon pro kg Körpergewicht und Woche behandelt wurden. Die Diagnose iGHD wurde gestellt bei einer mittleren nächtlichen Spontansekretion von <3,5ng/ml GH in Verbindung mit <10ng/ml GH in zwei GH-Stimulationstests mit Arginin oder Insulin. Die Diagnose NSD entsprechend bei <3,5ng/ml bzw. >10ng/ml GH. Es wurden folgende Parameter untersucht: Körpergröße/ -gewicht, Body-Mass-Index, Knochenalter, Insulin-like Growth Factor I (IGF-I), IGFBP-3 und Alkalische Phosphatase (AP). Die Körpergröße war bei beiden Diagnosen zu Therapiebeginn deutlich erniedrigt (iGHD: MW=-3,7+/-1,3SD; NSD: MW=-3,0+/-0,7SD). Die iGHD-Patienten zeigten zu Therapiebeginn signifikant niedrigere Werte für die Körpergröße, die IGF-I- und die IGFBP-3-Serumkonzentration (p<0,001). Während des ersten Jahres konnte bei beiden Diagnosen ein signifikanter Anstieg der Parameter Körpergröße, Körpergewicht, IGF-I, IGFBP-3 und AP festgestellt werden (p<0,001 außer AP[NSD]: p=0...

Transcription factor Ap-2 alpha is necessary for development of embryonic melanophores, autonomic neurons and pharyngeal skeleton in zebrafish

d’Alencon, Claudia; Eisen, Judith S.; Yelon, Deborah; Cornell, Robert A.; Bonde, Gregory; Gelb, Bruce D.; Allende Connelly, Miguel Luis; Li, Wei; Schoenebeck, Jeff; O’Brien, Erin K.
Fonte: ACADEMIC PRESS INC ELSEVIER SCIENCE Publicador: ACADEMIC PRESS INC ELSEVIER SCIENCE
Tipo: Artículo de revista
Português
Relevância na Pesquisa
36.748206%
The genes that control development of embryonic melanocytes are poorly defined. Although transcription factor Ap-2a is expressed in neural crest (NC) cells, its role in development of embryonic melanocytes and other neural crest derivatives is unclear because mouse Ap-2a mutants die before melanogenesis. We show that zebrafish embryos injected with morpholino antisense oligonucleotides complementary to ap-2a (ap-2a MO) complete early morphogenesis normally and have neural crest cells. Expression of c-kit, which encodes the receptor for the Steel ligand, is reduced in these embryos, and, similar to zebrafish c-kit mutant embryos, embryonic melanophores are reduced in number and migration. The effects of ap-2a MO injected into heterozygous and homozygous c-kit mutants support the notion that Ap-2a works through C-kit and additional target genes to mediate melanophore cell number and migration. In contrast to c-kit mutant embryos, in ap-2a MO-injected embryos, melanophores are small and under-pigmented, and unexpectedly, analysis of mosaic embryos suggests Ap-2a regulates melanophore differentiation through cell non-autonomous targets. In addition to melanophore phenotypes, we document reduction of other neural crest derivatives in ap-2a MO-injected embryos...

Transcriptional activation by AP-2 is modulated by the oncogene DEK

Campillos, Mónica; García, Miguel Ángel; Valdivieso Amate, Fernando; Vázquez, Jesús
Fonte: Oxford University Press Publicador: Oxford University Press
Tipo: Artículo Formato: 122002 bytes; application/pdf
Português
Relevância na Pesquisa
36.716987%
Cell differentiation and development are highly regulated processes at the transcriptional level. One of the main transcription factors that regulate these processes is AP-2, a cell-type specific protein required for vertebrate development and embryogenesis. AP-2 also regulates apoptosis and cell-cycle specific events by interacting with the oncogene c-Myc. In searching for novel AP-2- interacting factors, using an affinity chromatography approach, we have observed that oncoprotein DEK interacts with AP-2 in vitro. The existence of an interaction between AP-2 and DEK in cellular cultures was demonstrated by expression of a tagged AP-2 form followed by immunodetection. By transient co-expression experiments using a reporter for APOE promoter activity we have found that DEK stimulates the transactivation activity of AP-2 over APOE promoter. Finally, electrophoretic mobility shift assays suggested that DEK enhances the DNA-binding activity of AP-2. Our data suggest a novel cellular function of DEK as a transcriptional co-activator; This work was supported by CICYT SAF 2000-0178 and 08.5/0065.1/2001 grants from Spanish Ministerio de Ciencia y Tecnología and from Comunidad Autónoma de Madrid, and by an institutional grant by Fundación Ramón Areces to CBMSO; Peer reviewed

Transcriptional activation by AP-2alpha is modulated by the oncogene DEK

Campillos, Mónica; García, Miguel Ángel; Valdivieso Amate, Fernando; Vázquez, Jesús
Fonte: Oxford University Press Publicador: Oxford University Press
Tipo: Artículo Formato: 122002 bytes; application/pdf
Português
Relevância na Pesquisa
36.716987%
Cell differentiation and development are highly regulated processes at the transcriptional level. One of the main transcription factors that regulate these processes is AP-2alpha, a cell-type specific protein required for vertebrate development and embryogenesis. AP-2alpha also regulates apoptosis and cell-cycle specific events by interacting with the oncogene c-Myc. In searching for novel AP-2alpha- interacting factors, using an affinity chromatography approach, we have observed that oncoprotein DEK interacts with AP-2alpha in vitro. The existence of an interaction between AP-2alpha and DEK in cellular cultures was demonstrated by expression of a tagged AP-2alpha form followed by immunodetection. By transient co-expression experiments using a reporter for APOE promoter activity we have found that DEK stimulates the transactivation activity of AP-2alpha over APOE promoter. Finally, electrophoretic mobility shift assays suggested that DEK enhances the DNA-binding activity of AP-2alpha. Our data suggest a novel cellular function of DEK as a transcriptional co-activator; This work was supported by CICYT SAF 2000-0178 and 08.5/0065.1/2001 grants from Spanish Ministerio de Ciencia y Tecnología and from Comunidad Autónoma de Madrid, and by an institutional grant by Fundación Ramón Areces to CBMSO; Peer reviewed

Fast regulation of AP-1 activity through interaction of lamin A/C, ERK1/2, and c-Fos at the nuclear envelope

González, José M.; Navarro, Ana; Casar, Berta; Crespo, Piero; Andrés, Vicente
Fonte: Rockefeller University Press Publicador: Rockefeller University Press
Tipo: Artículo Formato: 3870787 bytes; application/pdf
Português
Relevância na Pesquisa
36.602522%
This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication.; Sequestration of c-Fos at the nuclear envelope (NE) through interaction with A-type lamins suppresses AP-1-dependent transcription. We show here that c-Fos accumulation within the extraction-resistant nuclear fraction (ERNF) and its interaction with lamin A are reduced and enhanced by gain-of and loss-of ERK1/2 activity, respectively. Moreover, hindering ERK1/2-dependent phosphorylation of c-Fos attenuates its release from the ERNF induced by serum and promotes its interaction with lamin A. Accordingly, serum stimulation rapidly releases preexisting c-Fos from the NE via ERK1/2-dependent phosphorylation, leading to a fast activation of AP-1 before de novo c-Fos synthesis. Moreover, lamin A-null cells exhibit increased AP-1 activity and reduced levels of c-Fos phosphorylation. We also find that active ERK1/2 interacts with lamin A and colocalizes with c-Fos and A-type lamins at the NE. Thus, NE-bound ERK1/2 functions as a molecular switch for rapid mitogen-dependent AP-1 activation through phosphorylation-induced release of preexisting c-Fos from its inhibitory interaction with lamin A/C.; This work was supported by grants SAF2004-03057 and SAF2007-6211 (Spanish Ministry of Science and Innovation–MICINN...

Characterisation of the AP-3 adaptor-like complex

Peden, Andrew Alexander
Fonte: University of Cambridge; Department of Clinical Biochemistry Publicador: University of Cambridge; Department of Clinical Biochemistry
Tipo: Thesis; doctoral; PhD
Português
Relevância na Pesquisa
36.760518%
Clathrin coated vesicles were the first type of coated vesicle to be characterised. The coat consists of two components, clathrin and adaptor (or AP) complexes, the AP-1 complex is associated with the clathrin coated vesicles that bud from the TGN and the AP-2 complex is associated with the clathrin coated vesicles that bud from the plasma membrane. A new type of adaptor-like complex was discovered in our laboratory and was published in 1996. The complex has been shown to consist of two known proteins, beta3B and mu3B, and two unknown proteins of 160kD and 22kD. Unlike the conventional adaptor complexes this complex is not associated with clathrin. The aim of this thesis was to complete the characterisation of the adaptor-like complex and to establish its function. My studies have shown that, the adaptor-like complex consist of an alpha/gamma like subunit, delta, a beta subunit (beta3A/B), a mu subunit (mu3A/B) and a sigma subunit (sigma3A/B). We named the adaptor-like complex AP-3, by analogy with the AP-1 and AP-2 complexes. The AP-3 complex is localised to perinuclear and more peripheral membranes in non-neuronal cells, with little overlap with endocytic markers. The beta subunit of the AP-3 complex is the major target for phosphorylation. Analysis of mice with mutations in the beta3A subunit...

A region between -141 and -61 bp containing a proximal AP-1 is essential for constitutive expression of urokinase-type plasminogen activator receptor

Dang, J; Boyd, Douglas; Allgayer, H; Doe, W; Wang, Yang
Fonte: Blackwell Publishing Ltd Publicador: Blackwell Publishing Ltd
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
36.641606%
An 8.5-kb 5'-flanking region of the human urokinase-type plasminogen activator receptor (uPAR) gene was cloned and the detailed uPAR promoter region defined in an 188-bp fragment between bases -141 and +47 relative to the transcription-start site. 5;-Deletion to - 100 and -60 in the region abolished its promoter activity, indicating that an 81-bp segment between - 141 and -61, which contains a proximal AP-1 site at position -70, is required for uPAR promoter activity. Nuclear extracts from HCT116 cells contain proteins that specifically bind to the AP-1 site. Mutation of the AP-1 motif reduced uPAR promoter activity in comparison with the wild-types. Induction of uPAR expression by phorbol ester requires this AP-1 motif in colon cancer cells. Cotransfection with the c-jun and c-fos expression vectors stimulated the uPAR promoter activity four- to fivefold. These results demonstrate that the proximal AP-1 motif is responsible for ≃50% of the basal expression of the uPAR gene.

A role for Ets1, synergizing with AP-1 and GATA-3 in the regulation of IL-5 transcription in mouse Th2 lymphocytes

Wang, Jun; Shannon, M Frances; Young, Ian
Fonte: Oxford University Press Publicador: Oxford University Press
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
36.733875%
IL-5 is a key regulator of eosinophilic inflammation and is selectively expressed by antigen-activated Th2 lymphocytes. An important role for the proximal AP-1 and GATA sites in regulating IL-5 transcription is generally accepted but the significance of an adjacent Ets/NFAT site has remained unclear. We have investigated its role using the mouse Th2 clone D10.G4.1. Transcription of IL-5 reporter gene plasmids could be induced in D10 cells by phorbol myristate acetate/ cyclic adenosine monophosphate (PMA/cAMP) stimulation and significantly further enhanced by activation of the mitogen-activated protein (MAP) kinase pathways. Strong induction of IL-5 mRNA was also induced by PMA/ cAMP. Mutagenesis showed that the Ets/NFAT site is of critical importance along with the AP-1 and GATA sites in regulating IL-5 transcription stimulated by PMA/cAMP and MAP kinase activation. Transactivation was used to investigate the transcription factors which could function at the three sites and possible synergistic interactions. AP-1 (c-Fos/c-Jun) strongly induced IL-5 transcription and dominant negative AP-1 constructs confirmed that AP-1 plays an important role in regulating IL-5 expression. Ets1, unlike other members of the Ets/NFAT family, synergized strongly with AP-1 suggesting that Ets1 is the family member which functions at the Ets/NFAT site. AP-1/Ets1 transactivation also stimulated IL-5 mRNA expression. Ets1 binding to the proximal promoter region...