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Pesquisa : D05.500.139 [Categoria DeCS]
Referências encontradas : 614 [refinar]
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[PMID]:29016691
[Au] Autor:Zhou W; Wan Y; Guo R; Deng M; Deng K; Wang Z; Zhang Y; Wang F
[Ad] Endereço:Jiangsu Livestock Embryo Engineering Laboratory, Nanjing Agricultural University, Nanjing, Jiangsu, PR, China.
[Ti] Título:Generation of beta-lactoglobulin knock-out goats using CRISPR/Cas9.
[So] Source:PLoS One;12(10):e0186056, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Goat's milk, considered a substitute for cow's milk, has a high nutritional value. However, goat's milk contains various allergens, predominantly ß-lactoglobulin (BLG). In this study, we employed the CRISPR/Cas9 system to target the BLG locus in goat fibroblasts for sgRNA optimization and generate BLG knock-out goats through co-injection of Cas9 mRNA and small guide RNAs (sgRNAs) into goat embryos at the one-cell stage. We firstly tested sgRNA editing efficiencies in goat fibroblast cells, and approximately 8.00%-9.09% of the cells were modified in single sgRNA-guided targeting experiment. Among the kids, the genome-targeting efficiencies of single sgRNA were 12.5% (10 ng/µL sg1) and 0% (10 ng/µL sg2) and efficiencies of dual sgRNAs were 25.0% (25 ng/µL sg2+sg3 group) and 28.6% (50 ng/µL sg2+sg3 group). Relative expression of BLG in BLG knock-out goat mammary glands significantly (p < 0.01) decreased as well as other milk protein coding genes, such as CSN1S1, CSN1S2, CSN2, CSN3 and LALBA (p < 0.05). As expected, BLG protein had been abolished in the milk of the BLG knock-out goat. In addition, most of the targeted kids were chimeric (3/4), and their various body tissues were edited simultaneously. Our study thus provides a basis for optimizing the quality of goat milk, which can be applied to biomedical and agricultural research.
[Mh] Termos MeSH primário: Sistemas CRISPR-Cas
Deleção de Genes
Edição de Genes
Lactoglobulinas/genética
Leite/química
[Mh] Termos MeSH secundário: Alérgenos/genética
Animais
Animais Geneticamente Modificados
Complexo do Signalossomo COP9
Quimerismo
Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas
Transferência Embrionária/métodos
Embrião de Mamíferos
Feminino
Fibroblastos/citologia
Fibroblastos/metabolismo
Expressão Gênica
Loci Gênicos
Cabras
Lactação/fisiologia
Lactoglobulinas/deficiência
Masculino
Microinjeções
Proteínas Nucleares/genética
Proteínas Nucleares/metabolismo
Cultura Primária de Células
Proteínas Quinases/genética
Proteínas Quinases/metabolismo
Subunidades Proteicas/genética
Subunidades Proteicas/metabolismo
RNA Guia/genética
RNA Guia/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Allergens); 0 (Lactoglobulins); 0 (Nuclear Proteins); 0 (Protein Subunits); 0 (RNA, Guide); EC 2.7.- (Protein Kinases); EC 3.4.19.12 (COP9 Signalosome Complex)
[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:171011
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0186056


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[PMID]:28919423
[Au] Autor:Zhang H; Zhong A; Sun J; Chen M; Xie S; Zheng H; Wang Y; Yu Y; Guo L; Lu R
[Ad] Endereço:Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China; Department of Clinical Laboratory, Fudan University Shanghai Cancer Center, Shanghai, China.
[Ti] Título:COPS5 inhibition arrests the proliferation and growth of serous ovarian cancer cells via the elevation of p27 level.
[So] Source:Biochem Biophys Res Commun;493(1):85-93, 2017 Nov 04.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The fifth component of the COP9 signalosome complex (COPS5), which plays an essential role in ubiquitin-mediated protein degradation, has been found as a prognostic biomarker for multiple cancers, however, the role of COPS5 in serous ovarian cancer (SOC) remain to be clarified. In this study, we found that COPS5 expression was significantly increased in SOC cells and tissues compared with those controls. Mechanistically, COPS5 and p27was proved to interact with each other, with COPS5 acts as a negative regulator of p27. SOC cells with COPS5 depletion were arrested in G1/G0-phase and exhibited a reduced proliferation ability and an increased cytoplasmic p27 expression. Whereas, the cells were stuck at S-phase accompanied with an elevation of nucleus p27 expression after knocking down COPS6 or blocking COPS5 by CSN5i-3. Furthermore, inhibition of COPS5 resulted in an elevation of Akt expression and sensitized SOC cells to Akt inhibitor MK2206. Suppression of COPS5 and Akt offers a potential strategy for the treatment of SOC.
[Mh] Termos MeSH primário: Proliferação Celular
Inibidor de Quinase Dependente de Ciclina p27/metabolismo
Cistadenocarcinoma Seroso/metabolismo
Cistadenocarcinoma Seroso/patologia
Peptídeos e Proteínas de Sinalização Intracelular/metabolismo
Neoplasias Ovarianas/metabolismo
Neoplasias Ovarianas/patologia
Peptídeo Hidrolases/metabolismo
[Mh] Termos MeSH secundário: Complexo do Signalossomo COP9
Pontos de Checagem do Ciclo Celular
Feminino
Seres Humanos
Células Tumorais Cultivadas
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Intracellular Signaling Peptides and Proteins); 147604-94-2 (Cyclin-Dependent Kinase Inhibitor p27); EC 3.4.- (Peptide Hydrolases); EC 3.4.-.- (COPS5 protein, human); EC 3.4.19.12 (COP9 Signalosome Complex)
[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:170919
[St] Status:MEDLINE


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[PMID]:28619822
[Au] Autor:Suisse A; He D; Legent K; Treisman JE
[Ad] Endereço:Helen L. and Martin S. Kimmel Center at the Skirball Institute for Biomolecular Medicine and Department of Cell Biology, NYU School of Medicine, 540 First Avenue, New York, NY 10016, USA.
[Ti] Título:COP9 signalosome subunits protect Capicua from MAPK-dependent and -independent mechanisms of degradation.
[So] Source:Development;144(14):2673-2682, 2017 07 15.
[Is] ISSN:1477-9129
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The COP9 signalosome removes Nedd8 modifications from the Cullin subunits of ubiquitin ligase complexes, reducing their activity. Here, we show that mutations in the ( ) gene increase the activity of ubiquitin ligases that contain Cullin 1. Analysis of mutant phenotypes revealed a requirement for the COP9 signalosome to prevent ectopic expression of Epidermal growth factor receptor (EGFR) target genes. It does so by protecting Capicua, a transcriptional repressor of EGFR target genes, from EGFR pathway-dependent ubiquitylation by a Cullin 1/SKP1-related A/Archipelago E3 ligase and subsequent proteasomal degradation. The CSN1b subunit also maintains basal Capicua levels by protecting it from a separate mechanism of degradation that is independent of EGFR signaling. As a suppressor of tumor growth and metastasis, Capicua may be an important target of the COP9 signalosome in cancer.
[Mh] Termos MeSH primário: Proteínas de Drosophila/metabolismo
Drosophila melanogaster/genética
Drosophila melanogaster/metabolismo
Proteínas HMGB/metabolismo
Complexos Multiproteicos/metabolismo
Peptídeo Hidrolases/metabolismo
Proteínas Repressoras/metabolismo
[Mh] Termos MeSH secundário: Animais
Animais Geneticamente Modificados
Complexo do Signalossomo COP9
Proteínas Culina/genética
Proteínas Culina/metabolismo
Proteínas de Drosophila/genética
Drosophila melanogaster/crescimento & desenvolvimento
Olho/crescimento & desenvolvimento
Olho/metabolismo
Feminino
Genes de Insetos
Proteínas HMGB/genética
Sistema de Sinalização das MAP Quinases
Masculino
Modelos Biológicos
Complexos Multiproteicos/genética
Mutação
Peptídeo Hidrolases/genética
Subunidades Proteicas/genética
Subunidades Proteicas/metabolismo
Proteólise
Receptor do Fator de Crescimento Epidérmico/genética
Receptor do Fator de Crescimento Epidérmico/metabolismo
Receptores de Peptídeos de Invertebrados/genética
Receptores de Peptídeos de Invertebrados/metabolismo
Proteínas Repressoras/genética
Ubiquitinação
Asas de Animais/crescimento & desenvolvimento
Asas de Animais/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (Cullin 1); 0 (Cullin Proteins); 0 (Drosophila Proteins); 0 (HMGB Proteins); 0 (Multiprotein Complexes); 0 (Protein Subunits); 0 (Receptors, Invertebrate Peptide); 0 (Repressor Proteins); 0 (cic protein, Drosophila); EC 2.7.10.1 (Egfr protein, Drosophila); EC 2.7.10.1 (Receptor, Epidermal Growth Factor); EC 3.4.- (Peptide Hydrolases); EC 3.4.19.12 (COP9 Signalosome Complex)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171126
[Lr] Data última revisão:
171126
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170617
[St] Status:MEDLINE
[do] DOI:10.1242/dev.148767


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[PMID]:28479251
[Au] Autor:Zhang S; Hong Z; Chai Y; Liu Z; Du Y; Li Q; Liu Q
[Ad] Endereço:Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province 330006, China; Department of General Surgery, Jiangxi Children's Hospital, Nanchang, Jiangxi Province 330006, China.
[Ti] Título:CSN5 promotes renal cell carcinoma metastasis and EMT by inhibiting ZEB1 degradation.
[So] Source:Biochem Biophys Res Commun;488(1):101-108, 2017 Jun 17.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:CSN5 (also known as COPS5) is a newly characterized oncogene involved in various types of cancer. However, its expression pattern and biological functions in renal cell carcinoma (RCC) is unknown. Here, we found that CSN5 expression was elevated in RCC tissues than those in paired normal renal tissues. Additionally, we demonstrated that high CSN5 level was closely correlated with tumor progression and poor survival in RCC patients. Our results showed that increased expression of CSN5 was observed in RCC cell lines and knockdown of CSN5 significantly suppressed the migration and invasion of RCC cells in vitro and in vivo. Additionally, CSN5 contributes to the metastasis and EMT (epithelial-mesenchymal transition) of RCC cells. Further investigation revealed that CSN5 led to the metastasis and EMT activation of RCC cells through increasing ZEB1 expression. Mechanistically, we found that CSN5 directly bound ZEB1 and decreased its ubiquitination to enhance the protein stability of ZEB1 in RCC cells. Taken together, our data identified CSN5 as a critical oncoprotein involved in migration and invasion of RCC cells, which could serve as a potential therapeutic target in RCC patients.
[Mh] Termos MeSH primário: Carcinoma de Células Renais/metabolismo
Carcinoma de Células Renais/patologia
Transição Epitelial-Mesenquimal
Peptídeos e Proteínas de Sinalização Intracelular/metabolismo
Neoplasias Renais/metabolismo
Neoplasias Renais/patologia
Peptídeo Hidrolases/metabolismo
Homeobox 1 de Ligação a E-box em Dedo de Zinco/metabolismo
[Mh] Termos MeSH secundário: Complexo do Signalossomo COP9
Feminino
Seres Humanos
Peptídeos e Proteínas de Sinalização Intracelular/genética
Masculino
Meia-Idade
Metástase Neoplásica
Peptídeo Hidrolases/genética
Estabilidade Proteica
Células Tumorais Cultivadas
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Intracellular Signaling Peptides and Proteins); 0 (ZEB1 protein, human); 0 (Zinc Finger E-box-Binding Homeobox 1); EC 3.4.- (Peptide Hydrolases); EC 3.4.-.- (COPS5 protein, human); EC 3.4.19.12 (COP9 Signalosome Complex)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170509
[St] Status:MEDLINE


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[PMID]:28335020
[Au] Autor:Anttonen AK; Laari A; Kousi M; Yang YJ; Jääskeläinen T; Somer M; Siintola E; Jakkula E; Muona M; Tegelberg S; Lönnqvist T; Pihko H; Valanne L; Paetau A; Lun MP; Hästbacka J; Kopra O; Joensuu T; Katsanis N; Lehtinen MK; Palvimo JJ; Lehesjoki AE
[Ad] Endereço:The Folkhälsan Institute of Genetics, Haartmaninkatu 8, 00290 Helsinki, Finland.
[Ti] Título:ZNHIT3 is defective in PEHO syndrome, a severe encephalopathy with cerebellar granule neuron loss.
[So] Source:Brain;140(5):1267-1279, 2017 05 01.
[Is] ISSN:1460-2156
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Progressive encephalopathy with oedema, hypsarrhythmia, and optic atrophy (PEHO) syndrome is an early childhood onset, severe autosomal recessive encephalopathy characterized by extreme cerebellar atrophy due to almost total granule neuron loss. By combining homozygosity mapping in Finnish families with Sanger sequencing of positional candidate genes and with exome sequencing a homozygous missense substitution of leucine for serine at codon 31 in ZNHIT3 was identified as the primary cause of PEHO syndrome. ZNHIT3 encodes a nuclear zinc finger protein previously implicated in transcriptional regulation and in small nucleolar ribonucleoprotein particle assembly and thus possibly to pre-ribosomal RNA processing. The identified mutation affects a highly conserved amino acid residue in the zinc finger domain of ZNHIT3. Both knockdown and genome editing of znhit3 in zebrafish embryos recapitulate the patients' cerebellar defects, microcephaly and oedema. These phenotypes are rescued by wild-type, but not mutant human ZNHIT3 mRNA, suggesting that the patient missense substitution causes disease through a loss-of-function mechanism. Transfection of cell lines with ZNHIT3 expression vectors showed that the PEHO syndrome mutant protein is unstable. Immunohistochemical analysis of mouse cerebellar tissue demonstrated ZNHIT3 to be expressed in proliferating granule cell precursors, in proliferating and post-mitotic granule cells, and in Purkinje cells. Knockdown of Znhit3 in cultured mouse granule neurons and ex vivo cerebellar slices indicate that ZNHIT3 is indispensable for granule neuron survival and migration, consistent with the zebrafish findings and patient neuropathology. These results suggest that loss-of-function of a nuclear regulator protein underlies PEHO syndrome and imply that establishment of its spatiotemporal interaction targets will be the basis for developing therapeutic approaches and for improved understanding of cerebellar development.
[Mh] Termos MeSH primário: Edema Encefálico/genética
Edema Encefálico/patologia
Cerebelo/patologia
Doenças Neurodegenerativas/genética
Doenças Neurodegenerativas/patologia
Neurônios/patologia
Proteínas Nucleares/genética
Proteínas Nucleares/fisiologia
Atrofia Óptica/genética
Atrofia Óptica/patologia
Espasmos Infantis/genética
Espasmos Infantis/patologia
[Mh] Termos MeSH secundário: Animais
Complexo do Signalossomo COP9
Movimento Celular/genética
Movimento Celular/fisiologia
Sobrevivência Celular/genética
Sobrevivência Celular/fisiologia
Cerebelo/metabolismo
Edema/complicações
Edema/genética
Exoma/genética
Edição de Genes
Técnicas de Silenciamento de Genes
Seres Humanos
Camundongos
Microcefalia/complicações
Microcefalia/genética
Mutação de Sentido Incorreto/genética
Mutação de Sentido Incorreto/fisiologia
Neurônios/metabolismo
Proteínas Nucleares/biossíntese
Análise de Sequência de DNA
Fatores de Transcrição/biossíntese
Peixe-Zebra
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cops2 protein, mouse); 0 (Nuclear Proteins); 0 (TRIP3 protein, human); 0 (Transcription Factors); EC 3.4.19.12 (COP9 Signalosome Complex)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170324
[St] Status:MEDLINE
[do] DOI:10.1093/brain/awx040


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[PMID]:28173800
[Au] Autor:Schwarz A; Bonaterra GA; Schwarzbach H; Kinscherf R
[Ad] Endereço:Anatomy and Cell Biology, Department of Medical Cell Biology, University of Marburg, Robert-Koch-Straße 8, 35032, Marburg, Germany. anja.schwarz@staff.uni-marburg.de.
[Ti] Título:Oxidized LDL-induced JAB1 influences NF-κB independent inflammatory signaling in human macrophages during foam cell formation.
[So] Source:J Biomed Sci;24(1):12, 2017 Feb 07.
[Is] ISSN:1423-0127
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Oxidized low-density lipoprotein (oxLDL) mediates the transformation of macrophages (MΦ) to cholesterol-rich foam cells and the release of pro-inflammatory cytokines during atherogenesis. JAB1 (Jun activation domain binding protein-1) is present in all stages of human plaques, involved in the Toll-like receptor-mediated activation of p38 mitogen-activated protein kinase (MAPK) and controls nuclear factor-kappa B (NF-κB) activation. Thus, we were interested in the role of JAB1 during foam cell formation of MΦ after oxLDL exposition. METHODS AND RESULTS: We found that JAB1 was present in CD68-immunoreactive (-ir) MΦ in atherosclerotic plaques of apolipoprotein E knockout (ApoE ) mice after a high cholesterol/fat diet. Furthermore, differentiated human U937 MΦ - incubated with oxLDL (4 h) to induce foam cell formation - showed a significant increase of JAB1 (50 µg/ml: 1.39 + 0.15-fold; 100 µg/ml: 1.80 + 0.26-fold; 200 µg/ml: 2.05 + 0.30-fold; p < 0.05) on the protein level compared to the control. Independent from JAB1 silencing, we found an increase of total cholesterol (TC), free cholesterol (FC) and cholesteryl ester (CE) after oxLDL exposition. However, siJAB1-MФ showed a reduction of tumor necrosis factor-alpha (TNF-α) (36%; p < 0.05 vs. non-transfected MФ) and interleukin (IL)-6 (30%; p < 0.05 vs. non-transfected MФ) mRNA expression, as well as TNF-α (46%; p < 0.05 vs. non-transfected MФ) and IL-6 (32%; p < 0.05 vs. non-transfected MФ) protein secretion after oxLDL exposition. In parallel with an upregulation of inflammatory cytokines (TNF-α, IL-6) after oxLDL exposition, we found a significant (p < 0.05) increase of 37% in p38 MAPK activation after 4 h oxLDL-treatment, independent from NF-kB signaling. In this context, we showed regional co-localization of JAB1 with p38 MAPK in atherosclerotic plaques of ApoE mice. Moreover, we detected interaction of JAB1 with p38 MAPK in U937 cells. CONCLUSION: We demonstrate that oxLDL induces JAB1 expression and influences its cellular localization, whereby the p38 MAPK signaling pathway is modified with consequences for inflammation of human MΦ in foam cells and atherosclerotic lesions.
[Mh] Termos MeSH primário: Células Espumosas/metabolismo
Peptídeos e Proteínas de Sinalização Intracelular/biossíntese
Lipoproteínas LDL/farmacologia
Sistema de Sinalização das MAP Quinases/efeitos dos fármacos
NF-kappa B/metabolismo
Peptídeo Hidrolases/biossíntese
Placa Aterosclerótica/metabolismo
[Mh] Termos MeSH secundário: Animais
Complexo do Signalossomo COP9
Células Espumosas/patologia
Seres Humanos
Peptídeos e Proteínas de Sinalização Intracelular/genética
Camundongos
Camundongos Knockout
NF-kappa B/genética
Peptídeo Hidrolases/genética
Placa Aterosclerótica/genética
Placa Aterosclerótica/patologia
Células U937
Proteínas Quinases p38 Ativadas por Mitógeno/genética
Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Intracellular Signaling Peptides and Proteins); 0 (Lipoproteins, LDL); 0 (NF-kappa B); 0 (oxidized low density lipoprotein); EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases); EC 3.4.- (Peptide Hydrolases); EC 3.4.-.- (COPS5 protein, human); EC 3.4.19.12 (COP9 Signalosome Complex)
[Em] Mês de entrada:1703
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170209
[St] Status:MEDLINE
[do] DOI:10.1186/s12929-017-0320-5


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[PMID]:28053002
[Au] Autor:Hernández-Puga G; Mendoza A; León-Del-Río A; Orozco A
[Ad] Endereço:Departamento de Neurobiología Celular y MolecularInstituto de Neurobiología, Universidad Nacional Autónoma de México (UNAM), Querétaro, Mexico.
[Ti] Título:Jab1 is a T2-dependent coactivator or a T3-dependent corepressor of TRB1-mediated gene regulation.
[So] Source:J Endocrinol;232(3):451-459, 2017 Mar.
[Is] ISSN:1479-6805
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Thyroid hormones (THs) induce pleiotropic effects in vertebrates, mainly through the activation or repression of gene expression. These mechanisms involve thyroid hormone binding to thyroid hormone receptors, an event that is followed by the sequential recruitment of coactivator or corepressor proteins, which in turn modify the rate of transcription. In the present study, we looked for specific coregulators recruited by the long isoform of the teleostean thyroid hormone receptor beta 1 (L-Trb1) when bound to the bioactive TH, 3,5-T (T ). We found that jun activation domain-binding protein1 (Jab1) interacts with L-Trb1 + T complex. Using both the teleostean and human TRB1 isoforms, we characterized the Jab1-TRB1 by yeast two-hybrid, pull-down and transactivation assays. Our results showed that the TRB1-Jab1 interaction was ligand dependent and involved the single Jab1 nuclear receptor box, as well as the ligand-binding and N-terminal domains of TRB1. We also provide evidence of ligand-dependent, dual coregulatory properties of Jab1. Indeed, when T is bound to L-Trb1 or hTRB1, Jab1 acts as a coactivator of transcription, whereas it has corepressor activity when interacting with the T -bound S-Trb1 or hTRB1. These mechanisms could explain some of the pleiotropic actions exerted by THs to regulate diverse biological processes.
[Mh] Termos MeSH primário: Regulação da Expressão Gênica/efeitos dos fármacos
Proteínas/metabolismo
Receptores beta dos Hormônios Tireóideos/metabolismo
Hormônios Tireóideos/farmacologia
[Mh] Termos MeSH secundário: Animais
Complexo do Signalossomo COP9
Linhagem Celular
Relação Dose-Resposta a Droga
Peptídeos e Proteínas de Sinalização Intracelular
Proteínas/genética
Ratos
Receptores dos Hormônios Tireóideos/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Gps1 protein, rat); 0 (Intracellular Signaling Peptides and Proteins); 0 (Proteins); 0 (Receptors, Thyroid Hormone); 0 (Thyroid Hormone Receptors beta); 0 (Thyroid Hormones); EC 3.4.19.12 (COP9 Signalosome Complex)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170106
[St] Status:MEDLINE
[do] DOI:10.1530/JOE-16-0485


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[PMID]:27869306
[Au] Autor:Li P; Xie L; Gu Y; Li J; Xie J
[Ad] Endereço:Institute of Modern Biopharmaceuticals, State Key Laboratory Breeding Base of Eco-Environment and Bio-Resource of the Three Gorges Area, Key Laboratory of Eco-environments in Three Gorges Reservoir Region, Ministry of Education, School of Life Sciences, Southwest University, Beibei, Chongqing, China
[Ti] Título:Roles of Multifunctional COP9 Signalosome Complex in Cell Fate and Implications for Drug Discovery.
[So] Source:J Cell Physiol;232(6):1246-1253, 2017 Jun.
[Is] ISSN:1097-4652
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The eight subunits containing COP9 signalosome (CSN) complex, is highly conserved among eukaryotes. CSN, identified as a negative regulator of photomorphogenesis, has also been demonstrated to be important in proteolysis, cellular signal transduction and cell cycle regulation in various eukaryotic organisms. This review mainly summarizes the roles of CSN in cell cycle regulation, signal transduction and apoptosis, and its potential as diagnostic biomarkers, drug targets for cancer and infectious diseases. J. Cell. Physiol. 232: 1246-1253, 2017. © 2016 Wiley Periodicals, Inc.
[Mh] Termos MeSH primário: Linhagem da Célula
Descoberta de Drogas
Complexos Multiproteicos/metabolismo
Peptídeo Hidrolases/metabolismo
[Mh] Termos MeSH secundário: Animais
Antineoplásicos/uso terapêutico
Complexo do Signalossomo COP9
Seres Humanos
Modelos Biológicos
Neoplasias/tratamento farmacológico
Neoplasias/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Multiprotein Complexes); EC 3.4.- (Peptide Hydrolases); EC 3.4.19.12 (COP9 Signalosome Complex)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161122
[St] Status:MEDLINE
[do] DOI:10.1002/jcp.25696


  9 / 614 MEDLINE  
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[PMID]:27546621
[Au] Autor:Hou J; Deng Q; Zhou J; Zou J; Zhang Y; Tan P; Zhang W; Cui H
[Ad] Endereço:Cell Biology Laboratory, State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing, China.
[Ti] Título:CSN6 controls the proliferation and metastasis of glioblastoma by CHIP-mediated degradation of EGFR.
[So] Source:Oncogene;36(8):1134-1144, 2017 Feb 23.
[Is] ISSN:1476-5594
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:CSN6, a critical subunit of the constitutive photomorphogenesis 9 (COP9) signalosome (CSN), has received attention as a regulator of the degradation of cancer-related proteins such as p53, c-myc and c-Jun, through the ubiquitin-proteasome system, suggesting its importance in cancerogenesis. However, the biological functions and molecular mechanisms of CSN6 in glioblastoma (GBM) remain poorly understood. Here, we report that GBM tumors overexpressed CSN6 compared with normal brain tissues and that CSN6 promoted GBM cell proliferation, migration, invasion and tumorigenesis. Erlotinib, a small-molecule epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, was used to reveal that the proliferative and metastatic effects of CSN6 on GBM cells were EGFR dependent. We also found that CSN6 positively regulated EGFR stability via reduced levels of EGFR ubiquitination, thereby elevating steady expression of EGFR. In addition, this study is the first description of a novel role for the CSN6-interacting E3 ligase, CHIP (carboxyl terminus of heat-shock protein 70-interacting protein), regulating EGFR ubiquitination in cancer cells. We showed that CSN6 associated with CHIP and led to CHIP destabilization by increasing CHIP self-ubiquitination. Moreover, CSN6 decreased CHIP expression and increased EGFR expression in the tumor samples. Deregulation of this axis promoted GBM cell's proliferation and metastasis. Thus, our study provides insights into the applicability of using the CSN6-CHIP-EGFR axis as a potential therapeutic target in cancer.
[Mh] Termos MeSH primário: Proteínas Adaptadoras de Transdução de Sinal/metabolismo
Movimento Celular
Proliferação Celular
Glioblastoma/patologia
Receptor do Fator de Crescimento Epidérmico/metabolismo
Ubiquitina-Proteína Ligases/metabolismo
[Mh] Termos MeSH secundário: Proteínas Adaptadoras de Transdução de Sinal/genética
Animais
Apoptose
Biomarcadores Tumorais
Complexo do Signalossomo COP9
Feminino
Glioblastoma/genética
Glioblastoma/metabolismo
Seres Humanos
Camundongos
Camundongos Endogâmicos NOD
Camundongos SCID
Estadiamento de Neoplasias
Prognóstico
Estabilidade Proteica
Receptor do Fator de Crescimento Epidérmico/genética
Transdução de Sinais
Células Tumorais Cultivadas
Ubiquitina/metabolismo
Ubiquitina-Proteína Ligases/genética
Ubiquitinação
Ensaios Antitumorais Modelo de Xenoenxerto
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Adaptor Proteins, Signal Transducing); 0 (Biomarkers, Tumor); 0 (COPS6 protein, human); 0 (Ubiquitin); EC 2.3.2.27 (STUB1 protein, human); EC 2.3.2.27 (Ubiquitin-Protein Ligases); EC 2.7.10.1 (EGFR protein, human); EC 2.7.10.1 (Receptor, Epidermal Growth Factor); EC 3.4.19.12 (COP9 Signalosome Complex)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160823
[St] Status:MEDLINE
[do] DOI:10.1038/onc.2016.280


  10 / 614 MEDLINE  
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[PMID]:27524414
[Au] Autor:Pan Y; Wang S; Su B; Zhou F; Zhang R; Xu T; Zhang R; Leventaki V; Drakos E; Liu W; Claret FX
[Ad] Endereço:Department of Pathology, Affiliated Hospital, Wuxi Medical School, Jiangnan University, Wuxi, China.
[Ti] Título:Stat3 contributes to cancer progression by regulating Jab1/Csn5 expression.
[So] Source:Oncogene;36(8):1069-1079, 2017 Feb 23.
[Is] ISSN:1476-5594
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Our previous studies demonstrated that Jab1/Csn5 overexpression is correlated with low survival rates in cancer patients, including nasopharyngeal carcinoma (NPC), breast cancer and hepatocellular carcinoma, and contributes to NPC's resistance to radiotherapy and cisplatin by regulating DNA damage and repair pathways. However, the molecular mechanism by which Jab1/Csn5 expression is upregulated in NPCs has yet to be determined. In the present study, we identified the upstream regulator of Jab1/Csn5 expression and demonstrated its role in intrinsic resistance of NPC cells to treatment with cisplatin. Signal transducer and activator of transcription-3 (Stat3) expression correlates with and contributes to Jab1/Csn5 transcription. Consistently, silencing of Stat3 in tumors reduced Jab1/Csn5 expression, thereby sensitizing NPC cells to cisplatin-induced apoptosis both in vitro and in vivo. Mechanistically, Stat3 transcriptionally regulated Jab1/Csn5. Furthermore, high mRNA expression levels of Stat3 or Jab1 in colon cancer, breast cancer and glioblastoma are associated with significantly shorter survival times from the R2 online database. These findings identify a novel Stat3-Jab1/Csn5 signaling axis in cancer pathogenesis with therapeutic and prognostic relevance.
[Mh] Termos MeSH primário: Biomarcadores Tumorais/metabolismo
Carcinoma/patologia
Regulação Neoplásica da Expressão Gênica
Inflamação/patologia
Peptídeos e Proteínas de Sinalização Intracelular/genética
Neoplasias Nasofaríngeas/patologia
Peptídeo Hidrolases/genética
Fator de Transcrição STAT3/metabolismo
[Mh] Termos MeSH secundário: Adolescente
Adulto
Idoso
Animais
Apoptose
Biomarcadores Tumorais/genética
Complexo do Signalossomo COP9
Carcinoma/genética
Carcinoma/metabolismo
Proliferação Celular
Progressão da Doença
Feminino
Seguimentos
Seres Humanos
Inflamação/genética
Inflamação/metabolismo
Peptídeos e Proteínas de Sinalização Intracelular/metabolismo
Masculino
Camundongos
Camundongos Nus
Meia-Idade
Neoplasias Nasofaríngeas/genética
Neoplasias Nasofaríngeas/metabolismo
Estadiamento de Neoplasias
Peptídeo Hidrolases/metabolismo
Prognóstico
Fator de Transcrição STAT3/genética
Transdução de Sinais
Ativação Transcricional
Células Tumorais Cultivadas
Ensaios Antitumorais Modelo de Xenoenxerto
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers, Tumor); 0 (Intracellular Signaling Peptides and Proteins); 0 (STAT3 Transcription Factor); 0 (STAT3 protein, human); EC 3.4.- (Peptide Hydrolases); EC 3.4.-.- (COPS5 protein, human); EC 3.4.19.12 (COP9 Signalosome Complex)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160816
[St] Status:MEDLINE
[do] DOI:10.1038/onc.2016.271



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