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Pesquisa : D12.776.835.725.868.124 [Categoria DeCS]
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[PMID]:28810145
[Au] Autor:Robertson AG; Shih J; Yau C; Gibb EA; Oba J; Mungall KL; Hess JM; Uzunangelov V; Walter V; Danilova L; Lichtenberg TM; Kucherlapati M; Kimes PK; Tang M; Penson A; Babur O; Akbani R; Bristow CA; Hoadley KA; Iype L; Chang MT; Cherniack AD; Benz C; Mills GB; Verhaak RGW; Griewank KG; Felau I; Zenklusen JC; Gershenwald JE; Schoenfield L; Lazar AJ; Abdel-Rahman MH; Roman-Roman S; Stern MH; Cebulla CM; Williams MD; Jager MJ; Coupland SE; Esmaeli B; Kandoth C; Woodman SE; TCGA Research Network
[Ad] Endereço:Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, BC V5Z 4S6, Canada.
[Ti] Título:Integrative Analysis Identifies Four Molecular and Clinical Subsets in Uveal Melanoma.
[So] Source:Cancer Cell;32(2):204-220.e15, 2017 Aug 14.
[Is] ISSN:1878-3686
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Comprehensive multiplatform analysis of 80 uveal melanomas (UM) identifies four molecularly distinct, clinically relevant subtypes: two associated with poor-prognosis monosomy 3 (M3) and two with better-prognosis disomy 3 (D3). We show that BAP1 loss follows M3 occurrence and correlates with a global DNA methylation state that is distinct from D3-UM. Poor-prognosis M3-UM divide into subsets with divergent genomic aberrations, transcriptional features, and clinical outcomes. We report change-of-function SRSF2 mutations. Within D3-UM, EIF1AX- and SRSF2/SF3B1-mutant tumors have distinct somatic copy number alterations and DNA methylation profiles, providing insight into the biology of these low- versus intermediate-risk clinical mutation subtypes.
[Mh] Termos MeSH primário: Biomarcadores Tumorais/genética
Metilação de DNA
Regulação Neoplásica da Expressão Gênica
Melanoma/genética
Mutação
Neoplasias Uveais/genética
[Mh] Termos MeSH secundário: Variações do Número de Cópias de DNA
Fator de Iniciação 1 em Eucariotos/genética
Seres Humanos
Melanoma/classificação
Monossomia
Fosfoproteínas/genética
Prognóstico
Fatores de Processamento de RNA/genética
Fatores de Processamento de Serina-Arginina/genética
Proteínas Supressoras de Tumor/genética
Ubiquitina Tiolesterase/genética
Neoplasias Uveais/classificação
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers, Tumor); 0 (Eukaryotic Initiation Factor-1); 0 (Phosphoproteins); 0 (RNA Splicing Factors); 0 (SF3B1 protein, human); 0 (SRSF3 protein, human); 0 (Tumor Suppressor Proteins); 0 (eukaryotic peptide initiation factor-1A); 170974-22-8 (Serine-Arginine Splicing Factors); EC 3.1.2.15 (BAP1 protein, human); EC 3.4.19.12 (Ubiquitin Thiolesterase)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170930
[Lr] Data última revisão:
170930
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170816
[St] Status:MEDLINE


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[PMID]:28700778
[Au] Autor:Scholz SL; Möller I; Reis H; Süßkind D; van de Nes JAP; Leonardelli S; Schilling B; Livingstone E; Schimming T; Paschen A; Sucker A; Murali R; Steuhl KP; Schadendorf D; Westekemper H; Griewank KG
[Ad] Endereço:Department of Ophthalmology, University Hospital Essen, West German Cancer Center, University Duisburg-Essen and the German Cancer Consortium (DKTK), Essen, Germany.
[Ti] Título:Frequent GNAQ, GNA11, and EIF1AX Mutations in Iris Melanoma.
[So] Source:Invest Ophthalmol Vis Sci;58(9):3464-3470, 2017 Jul 01.
[Is] ISSN:1552-5783
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Purpose: The most common malignant intraocular tumors with a high mortality in adults are uveal melanomas. Uveal melanomas arise most frequently in the choroid or ciliary body (97%) and rarely in the iris (3%). Whereas conjunctival and posterior uveal (ciliary body and choroidal) melanomas have been studied in more detail genetically, little data exist regarding iris melanomas. Methods: In our study, we genetically analyzed 19 iris melanomas, 8 ciliary body melanomas, 3 ring melanomas, and 4 iris nevi. A targeted next-generation sequencing approach was applied, covering the mutational hotspot regions of nine genes known to be mutated in conjunctival and uveal melanoma (BRAF, NRAS, KIT, GNAQ, GNA11, CYSLTR2, SF3B1, EIF1AX, and BAP1). Results: Activating GNAQ or GNA11 hotspot mutations were detected in a mutually exclusive fashion in 84% (16/19) of iris melanomas. EIF1AX gene mutations also were frequent, detected in 42% (8/19) of iris melanomas. In 4 iris nevi, one GNAQ mutation was identified. GNAQ, GNA11, EIF1AX, and BAP1 mutations were identified at varying frequencies in ciliary body and ring melanomas. Conclusions: In this most comprehensive genetic analysis of iris melanomas published to date, we find iris melanomas to be related genetically to choroidal and ciliary body melanomas, frequently harboring GNAQ, GNA11, and EIF1AX mutations. Future studies will need to assess if screening mutation profiles in iris melanomas may be of diagnostic or prognostic value.
[Mh] Termos MeSH primário: DNA de Neoplasias/genética
Fator de Iniciação 1 em Eucariotos/genética
Subunidades alfa Gq-G11 de Proteínas de Ligação ao GTP/genética
Subunidades alfa de Proteínas de Ligação ao GTP/genética
Neoplasias da Íris/genética
Melanoma/genética
Mutação
[Mh] Termos MeSH secundário: Idoso
Análise Mutacional de DNA
Fator de Iniciação 1 em Eucariotos/metabolismo
Feminino
Subunidades alfa de Proteínas de Ligação ao GTP/metabolismo
Subunidades alfa Gq-G11 de Proteínas de Ligação ao GTP/metabolismo
Seres Humanos
Neoplasias da Íris/metabolismo
Neoplasias da Íris/patologia
Masculino
Melanoma/metabolismo
Melanoma/patologia
Meia-Idade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (DNA, Neoplasm); 0 (Eukaryotic Initiation Factor-1); 0 (GNA11 protein, human); 0 (GNAQ protein, human); 0 (GTP-Binding Protein alpha Subunits); 0 (eukaryotic peptide initiation factor-1A); EC 3.6.5.1 (GTP-Binding Protein alpha Subunits, Gq-G11)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170809
[Lr] Data última revisão:
170809
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170713
[St] Status:MEDLINE
[do] DOI:10.1167/iovs.17-21838


  3 / 264 MEDLINE  
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[PMID]:28646021
[Au] Autor:Etemadmoghadam D; Azar WJ; Lei Y; Moujaber T; Garsed DW; Kennedy CJ; Fereday S; Mitchell C; Chiew YE; Hendley J; Sharma R; Harnett PR; Li J; Christie EL; Patch AM; George J; Au-Yeung G; Mir Arnau G; Holloway TP; Semple T; Pearson JV; Waddell N; Grimmond SM; Köbel M; Rizos H; Lomakin IB; Bowtell DDL; deFazio A; Australian Ovarian Cancer Study Group
[Ad] Endereço:Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
[Ti] Título: and Mutations Co-occur and Cooperate in Low-Grade Serous Ovarian Carcinomas.
[So] Source:Cancer Res;77(16):4268-4278, 2017 Aug 15.
[Is] ISSN:1538-7445
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Low-grade serous ovarian carcinomas (LGSC) are associated with a poor response to chemotherapy and are molecularly characterized by RAS pathway activation. Using exome and whole genome sequencing, we identified recurrent mutations in the protein translational regulator and in , and RAS pathway mutations were mutually exclusive; however, we found significant co-occurrence of mutations in and Missense mutations were clustered at the N-terminus of the protein in a region associated with its role in ensuring translational initiation fidelity. Coexpression of mutant and proteins promoted proliferation and clonogenic survival in LGSC cells, providing the first example of co-occurring, growth-promoting mutational events in ovarian cancer. .
[Mh] Termos MeSH primário: Cistadenocarcinoma Seroso/genética
Fator de Iniciação 1 em Eucariotos/genética
GTP Fosfo-Hidrolases/genética
Proteínas de Membrana/genética
Mutação
Neoplasias Ovarianas/genética
[Mh] Termos MeSH secundário: Linhagem Celular Tumoral
Cistadenocarcinoma Seroso/patologia
Fator de Iniciação 1 em Eucariotos/biossíntese
Feminino
Técnicas de Silenciamento de Genes
Seres Humanos
Mutagênese Sítio-Dirigida
Gradação de Tumores
Estadiamento de Neoplasias
Neoplasias Ovarianas/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Eukaryotic Initiation Factor-1); 0 (Membrane Proteins); 0 (eukaryotic peptide initiation factor-1A); EC 3.6.1.- (GTP Phosphohydrolases); EC 3.6.1.- (NRAS protein, human)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170929
[Lr] Data última revisão:
170929
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170625
[St] Status:MEDLINE
[do] DOI:10.1158/0008-5472.CAN-16-2224


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[PMID]:28594900
[Au] Autor:Johnson CP; Kim IK; Esmaeli B; Amin-Mansour A; Treacy DJ; Carter SL; Hodis E; Wagle N; Seepo S; Yu X; Lane AM; Gragoudas ES; Vazquez F; Nickerson E; Cibulskis K; McKenna A; Gabriel SB; Getz G; Van Allen EM; 't Hoen PAC; Garraway LA; Woodman SE
[Ad] Endereço:Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, United States of America.
[Ti] Título:Systematic genomic and translational efficiency studies of uveal melanoma.
[So] Source:PLoS One;12(6):e0178189, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:To further our understanding of the somatic genetic basis of uveal melanoma, we sequenced the protein-coding regions of 52 primary tumors and 3 liver metastases together with paired normal DNA. Known recurrent mutations were identified in GNAQ, GNA11, BAP1, EIF1AX, and SF3B1. The role of mutated EIF1AX was tested using loss of function approaches including viability and translational efficiency assays. Knockdown of both wild type and mutant EIF1AX was lethal to uveal melanoma cells. We probed the function of N-terminal tail EIF1AX mutations by performing RNA sequencing of polysome-associated transcripts in cells expressing endogenous wild type or mutant EIF1AX. Ribosome occupancy of the global translational apparatus was sensitive to suppression of wild type but not mutant EIF1AX. Together, these studies suggest that cells expressing mutant EIF1AX may exhibit aberrant translational regulation, which may provide clonal selective advantage in the subset of uveal melanoma that harbors this mutation.
[Mh] Termos MeSH primário: Genoma Humano
Melanoma/genética
Biossíntese de Proteínas/genética
Neoplasias Uveais/genética
[Mh] Termos MeSH secundário: Adulto
Idoso
Idoso de 80 Anos ou mais
Fator de Iniciação 1 em Eucariotos/genética
Feminino
Seres Humanos
Masculino
Melanoma/patologia
Meia-Idade
Mutação
Neoplasias Uveais/patologia
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Eukaryotic Initiation Factor-1); 0 (eukaryotic peptide initiation factor-1A)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170918
[Lr] Data última revisão:
170918
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170609
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0178189


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[PMID]:28584194
[Au] Autor:Haimov O; Sinvani H; Martin F; Ulitsky I; Emmanuel R; Tamarkin-Ben-Harush A; Vardy A; Dikstein R
[Ad] Endereço:Department of Biomolecular Sciences, The Weizmann Institute of Science, Rehovot, Israel.
[Ti] Título:Efficient and Accurate Translation Initiation Directed by TISU Involves RPS3 and RPS10e Binding and Differential Eukaryotic Initiation Factor 1A Regulation.
[So] Source:Mol Cell Biol;37(15), 2017 Aug 01.
[Is] ISSN:1098-5549
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Canonical translation initiation involves ribosomal scanning, but short 5' untranslated region (5'UTR) mRNAs are translated in a scanning-independent manner. The extent and mechanism of scanning-independent translation are not fully understood. Here we report that short 5'UTR mRNAs constitute a substantial fraction of the translatome. Short 5'UTR mRNAs are enriched with TISU ( ranslation nitiator of hort 5' TR), a 12-nucleotide element directing efficient scanning-independent translation. Comprehensive mutagenesis revealed that each AUG codon-flanking nucleotide of TISU contributes to translational strength, but only a few are important for accuracy. Using site-specific UV cross-linking of ribosomal complexes assembled on TISU mRNA, we demonstrate specific binding of TISU to ribosomal proteins at the E and A sites. We identified RPS3 as the major TISU binding protein in the 48S complex A site. Upon 80S complex formation, RPS3 interaction is weakened and switched to RPS10e (formerly called RPS10). We further demonstrate that TISU is particularly dependent on eukaryotic initiation factor 1A (eIF1A) which interacts with both RPS3 and RPS10e. Our findings suggest that the cap-recruited ribosome specifically binds the TISU nucleotides at the A and E sites in cooperation with eIF1A to promote scanning arrest.
[Mh] Termos MeSH primário: Regiões 5´ não Traduzidas
Fator de Iniciação 1 em Eucariotos/metabolismo
Biossíntese de Proteínas
Proteínas Ribossômicas/metabolismo
[Mh] Termos MeSH secundário: Animais
Linhagem Celular
Células HEK293
Células HeLa
Seres Humanos
Camundongos
Ligação Proteica
Mapas de Interação de Proteínas
RNA Mensageiro/genética
RNA Mensageiro/metabolismo
Ribossomos/genética
Ribossomos/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (5' Untranslated Regions); 0 (Eukaryotic Initiation Factor-1); 0 (RNA, Messenger); 0 (RPS10 protein, human); 0 (RPS3 protein, human); 0 (Ribosomal Proteins); 0 (eukaryotic peptide initiation factor-1A)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170919
[Lr] Data última revisão:
170919
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170607
[St] Status:MEDLINE


  6 / 264 MEDLINE  
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[PMID]:28534687
[Au] Autor:Nikiforov YE
[Ti] Título:ROLE OF MOLECULAR MARKERS IN THYROID NODULE MANAGEMENT: THEN AND NOW.
[So] Source:Endocr Pract;23(8):979-988, 2017 Aug.
[Is] ISSN:1530-891X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: To describe the evolution and clinical utility of molecular testing for thyroid nodules and cancer achieved over the last 2 decades. METHODS: Scientific reports on thyroid cancer genetics and molecular diagnostics in thyroid nodules. RESULTS: Over the last 2 decades, our understanding of the genetic mechanisms of thyroid cancer has dramatically expanded, such that most thyroid cancers now have known gene driver events. This knowledge provides the basis for establishing and further improving molecular tests for thyroid nodules and cancer and for the introduction of new entities such as noninvasive follicular thyroid neoplasm with papillary-like nuclear features. The progress with molecular tests for thyroid nodules started in the 1990s from demonstrating feasibility of detecting various molecular alterations in fine-needle aspiration (FNA) material collected from thyroid nodules. It was followed by the introduction of the first single-gene mutational markers, such as BRAF, and a small mutational panel into clinical practice in the mid 2000s. Currently, several more advanced molecular tests are available for clinical use. They are based on multiple molecular markers and have increasing impact on the clinical management of patients with thyroid nodules. CONCLUSION: The evolution of molecular tests for thyroid nodules followed the discovery of various diagnostic and prognostic molecular markers of thyroid cancer that can be applied to thyroid FNA samples to inform more individualized management of these patients. ABBREVIATIONS: FNA = fine-needle aspiration miRNA = micro RNA NGS = next-generation sequencing NIFTP = noninvasive follicular thyroid neoplasm with papillary-like nuclear features NPV = negative predictive value PPV = positive predictive value PTC = papillary thyroid carcinoma RAI = radioactive iodine.
[Mh] Termos MeSH primário: Adenocarcinoma Folicular/genética
Biomarcadores Tumorais/genética
Carcinoma/genética
Neoplasias da Glândula Tireoide/genética
Nódulo da Glândula Tireoide/genética
[Mh] Termos MeSH secundário: Adenocarcinoma Folicular/diagnóstico
Adenocarcinoma Folicular/patologia
Biópsia por Agulha Fina
Carcinoma/diagnóstico
Carcinoma/patologia
Carcinoma Papilar
Fator de Iniciação 1 em Eucariotos/genética
GTP Fosfo-Hidrolases/genética
Fusão Gênica
Seres Humanos
Proteínas de Membrana/genética
Mutação
Valor Preditivo dos Testes
Prognóstico
Proteínas Proto-Oncogênicas B-raf/genética
Proteínas Proto-Oncogênicas p21(ras)/genética
Neoplasias da Glândula Tireoide/diagnóstico
Neoplasias da Glândula Tireoide/patologia
Nódulo da Glândula Tireoide/diagnóstico
Nódulo da Glândula Tireoide/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Biomarkers, Tumor); 0 (Eukaryotic Initiation Factor-1); 0 (KRAS protein, human); 0 (Membrane Proteins); 0 (eukaryotic peptide initiation factor-1A); EC 2.7.11.1 (BRAF protein, human); EC 2.7.11.1 (Proto-Oncogene Proteins B-raf); EC 3.6.1.- (GTP Phosphohydrolases); EC 3.6.1.- (NRAS protein, human); EC 3.6.5.2 (HRAS protein, human); EC 3.6.5.2 (Proto-Oncogene Proteins p21(ras))
[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:170524
[St] Status:MEDLINE
[do] DOI:10.4158/EP171805.RA


  7 / 264 MEDLINE  
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[PMID]:28520920
[Au] Autor:Jakobsson ME; Malecki J; Nilges BS; Moen A; Leidel SA; Falnes PØ
[Ad] Endereço:Department of Biosciences, Faculty of Mathematics and Natural Sciences, University of Oslo, Oslo 0316, Norway.
[Ti] Título:Methylation of human eukaryotic elongation factor alpha (eEF1A) by a member of a novel protein lysine methyltransferase family modulates mRNA translation.
[So] Source:Nucleic Acids Res;45(14):8239-8254, 2017 Aug 21.
[Is] ISSN:1362-4962
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Many cellular proteins are methylated on lysine residues and this has been most intensively studied for histone proteins. Lysine methylations on non-histone proteins are also frequent, but in most cases the functional significance of the methylation event, as well as the identity of the responsible lysine (K) specific methyltransferase (KMT), remain unknown. Several recently discovered KMTs belong to the so-called seven-ß-strand (7BS) class of MTases and we have here investigated an uncharacterized human 7BS MTase currently annotated as part of the endothelin converting enzyme 2, but which should be considered a separate enzyme. Combining in vitro enzymology and analyzes of knockout cells, we demonstrate that this MTase efficiently methylates K36 in eukaryotic translation elongation factor 1 alpha (eEF1A) in vitro and in vivo. We suggest that this novel KMT is named eEF1A-KMT4 (gene name EEF1AKMT4), in agreement with the recently established nomenclature. Furthermore, by ribosome profiling we show that the absence of K36 methylation affects translation dynamics and changes translation speed of distinct codons. Finally, we show that eEF1A-KMT4 is part of a novel family of human KMTs, defined by a shared sequence motif in the active site and we demonstrate the importance of this motif for catalytic activity.
[Mh] Termos MeSH primário: Fator de Iniciação 1 em Eucariotos/metabolismo
Metiltransferases/metabolismo
Biossíntese de Proteínas
RNA Mensageiro/metabolismo
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Sequência de Bases
Linhagem Celular
Eletroforese em Gel de Poliacrilamida
Fator de Iniciação 1 em Eucariotos/genética
Técnicas de Inativação de Genes
Seres Humanos
Lisina/genética
Lisina/metabolismo
Metilação
Metiltransferases/genética
Filogenia
RNA Mensageiro/genética
Homologia de Sequência de Aminoácidos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Eukaryotic Initiation Factor-1); 0 (RNA, Messenger); 0 (eukaryotic peptide initiation factor-1A); EC 2.1.1.- (DOT1L protein, human); EC 2.1.1.- (Methyltransferases); K3Z4F929H6 (Lysine)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171023
[Lr] Data última revisão:
171023
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170519
[St] Status:MEDLINE
[do] DOI:10.1093/nar/gkx432


  8 / 264 MEDLINE  
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[PMID]:28025327
[Au] Autor:Tsai NP; Wilkerson JR; Guo W; Huber KM
[Ad] Endereço:Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX, USA.
[Ti] Título:FMRP-dependent Mdm2 dephosphorylation is required for MEF2-induced synapse elimination.
[So] Source:Hum Mol Genet;26(2):293-304, 2017 Jan 15.
[Is] ISSN:1460-2083
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The Myocyte Enhancer Factor 2 (MEF2) transcription factors suppress an excitatory synapse number by promoting degradation of the synaptic scaffold protein, postsynaptic density protein 95 (PSD-95), a process that is deficient in the mouse model of Fragile X Syndrome, Fmr1 KO. How MEF2 activation results in PSD-95 degradation and why this is defective in Fmr1 KO neurons is unknown. Here we report that MEF2 induces a Protein phosphatase 2A (PP2A)-mediated dephosphorylation of murine double minute-2 (Mdm2), the ubiquitin E3 ligase for PSD-95, which results in nuclear export and synaptic accumulation of Mdm2 as well as PSD-95 degradation and synapse elimination. In Fmr1 KO neurons, Mdm2 is hyperphosphorylated, nuclear localized basally, and unaffected by MEF2 activation, which our data suggest due to an enhanced interaction with Eukaryotic Elongation Factor 1α (EF1α), whose protein levels are elevated in Fmr1 KO. Expression of a dephosphomimetic of Mdm2 rescues PSD-95 ubiquitination, degradation and synapse elimination in Fmr1 KO neurons. This work reveals detailed mechanisms of synapse elimination in health and a developmental brain disorder.
[Mh] Termos MeSH primário: Proteína do X Frágil de Retardo Mental/genética
Síndrome do Cromossomo X Frágil/genética
Guanilato Quinases/genética
Fatores de Transcrição MEF2/genética
Proteínas de Membrana/genética
Proteínas Proto-Oncogênicas c-mdm2/genética
[Mh] Termos MeSH secundário: Animais
Dendritos/metabolismo
Dendritos/patologia
Proteína 4 Homóloga a Disks-Large
Fator de Iniciação 1 em Eucariotos/genética
Síndrome do Cromossomo X Frágil/patologia
Seres Humanos
Camundongos
Camundongos Knockout
Neurônios/metabolismo
Neurônios/patologia
Fosforilação
Proteína Fosfatase 2/genética
Proteólise
Sinapses/genética
Sinapses/patologia
Ubiquitinação/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Disks Large Homolog 4 Protein); 0 (Dlg4 protein, mouse); 0 (Eukaryotic Initiation Factor-1); 0 (Fmr1 protein, mouse); 0 (MEF2 Transcription Factors); 0 (Membrane Proteins); 139135-51-6 (Fragile X Mental Retardation Protein); EC 2.3.2.27 (Mdm2 protein, mouse); EC 2.3.2.27 (Proto-Oncogene Proteins c-mdm2); EC 2.7.4.8 (Guanylate Kinases); EC 3.1.3.16 (Protein Phosphatase 2)
[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:161228
[St] Status:MEDLINE
[do] DOI:10.1093/hmg/ddw386


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[PMID]:28009256
[Au] Autor:Jaafar ZA; Oguro A; Nakamura Y; Kieft JS
[Ad] Endereço:Department of Biochemistry and Molecular Genetics, University of Colorado Denver School of Medicine, Aurora, United States.
[Ti] Título:Translation initiation by the hepatitis C virus IRES requires eIF1A and ribosomal complex remodeling.
[So] Source:Elife;5, 2016 Dec 23.
[Is] ISSN:2050-084X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Internal ribosome entry sites (IRESs) are important RNA-based translation initiation signals, critical for infection by many pathogenic viruses. The hepatitis C virus (HCV) IRES is the prototype for the type 3 IRESs and is also invaluable for exploring principles of eukaryotic translation initiation, in general. Current mechanistic models for the type 3 IRESs are useful but they also present paradoxes, including how they can function both with and without eukaryotic initiation factor (eIF) 2. We discovered that eIF1A is necessary for efficient activity where it stabilizes tRNA binding and inspects the codon-anticodon interaction, especially important in the IRES' eIF2-independent mode. These data support a model in which the IRES binds preassembled translation preinitiation complexes and remodels them to generate eukaryotic initiation complexes with bacterial-like features. This model explains previous data, reconciles eIF2-dependent and -independent pathways, and illustrates how RNA structure-based control can respond to changing cellular conditions.
[Mh] Termos MeSH primário: Fator de Iniciação 1 em Eucariotos/metabolismo
Hepacivirus/fisiologia
Interações Hospedeiro-Patógeno
Sítios Internos de Entrada Ribossomal
Iniciação Traducional da Cadeia Peptídica
Ribossomos/metabolismo
Proteínas Virais/biossíntese
[Mh] Termos MeSH secundário: Linhagem Celular
Seres Humanos
Modelos Biológicos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Eukaryotic Initiation Factor-1); 0 (Internal Ribosome Entry Sites); 0 (Viral Proteins); 0 (eukaryotic peptide initiation factor-1A)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171010
[Lr] Data última revisão:
171010
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161224
[St] Status:MEDLINE


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[PMID]:27959936
[Au] Autor:Enos RT; Velázquez KT; Carson MS; McClellan JL; Nagarkatti P; Nagarkatti M; Davis JM; Murphy EA
[Ad] Endereço:Department of Pathology, Microbiology & Immunology, School of Medicine, University of South Carolina, Columbia, SC, United States of America.
[Ti] Título:A Low Dose of Dietary Quercetin Fails to Protect against the Development of an Obese Phenotype in Mice.
[So] Source:PLoS One;11(12):e0167979, 2016.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The purpose of this study was to examine the effect of a 40% high-fat diet (HFD) supplemented with a dietary attainable level of quercetin (0.02%) on body composition, adipose tissue (AT) inflammation, Non-Alcoholic Fatty-Liver Disease (NAFLD), and metabolic outcomes. Diets were administered for 16 weeks to C57BL/6J mice (n = 10/group) beginning at 4 weeks of age. Body composition and fasting blood glucose, insulin, and total cholesterol concentrations were examined intermittently. AT and liver mRNA expression (RT-PCR) of inflammatory mediators (F4/80, CD206 (AT only), CD11c (AT only) TLR-2 (AT only), TLR-4 (AT only), MCP-1, TNF-α, IL-6 (AT only), and IL-10 (AT only)) were measured along with activation of NFκB-p65, and JNK (western blot). Hepatic lipid accumulation, gene expression (RT-PCR) of hepatic metabolic markers (ACAC1, SREBP-1, PPAR-γ), protein content of Endoplasmic Reticulum (ER) Stress markers (BiP, phosphorylated and total EIF2α, phosphorylated and total IRE1α, CHOP), and hepatic oxidative capacity were assessed (western blot). Quercetin administration had no effect at mitigating increases in visceral AT, AT inflammation, hepatic steatosis, ER Stress, decrements in hepatic oxidative capacity, or the development of insulin resistance and hypercholesterolemia. In conclusion, 0.02% quercetin supplementation is not an effective therapy for attenuating HFD-induced obesity development. It is likely that a higher dose of quercetin supplementation is needed to elicit favorable outcomes in obesity.
[Mh] Termos MeSH primário: Antioxidantes/uso terapêutico
Obesidade/prevenção & controle
Fenótipo
Quercetina/uso terapêutico
[Mh] Termos MeSH secundário: Animais
Antioxidantes/administração & dosagem
Antioxidantes/farmacologia
Glicemia/metabolismo
Composição Corporal/efeitos dos fármacos
Quimiocinas/genética
Quimiocinas/metabolismo
Colesterol/sangue
Suplementos Nutricionais
Estresse do Retículo Endoplasmático
Endorribonucleases/genética
Endorribonucleases/metabolismo
Fator de Iniciação 1 em Eucariotos/metabolismo
Insulina/sangue
Fígado/efeitos dos fármacos
Fígado/metabolismo
MAP Quinase Quinase 4/genética
MAP Quinase Quinase 4/metabolismo
Masculino
Camundongos
Camundongos Endogâmicos C57BL
NF-kappa B/genética
NF-kappa B/metabolismo
Obesidade/tratamento farmacológico
Obesidade/metabolismo
Estresse Oxidativo
Proteínas Serina-Treonina Quinases/genética
Proteínas Serina-Treonina Quinases/metabolismo
Quercetina/administração & dosagem
Quercetina/farmacologia
Receptores Toll-Like/genética
Receptores Toll-Like/metabolismo
Fator de Transcrição CHOP/genética
Fator de Transcrição CHOP/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antioxidants); 0 (Blood Glucose); 0 (Chemokines); 0 (Ddit3 protein, mouse); 0 (Eukaryotic Initiation Factor-1); 0 (Insulin); 0 (NF-kappa B); 0 (Toll-Like Receptors); 0 (eukaryotic peptide initiation factor-1A); 147336-12-7 (Transcription Factor CHOP); 97C5T2UQ7J (Cholesterol); 9IKM0I5T1E (Quercetin); EC 2.7.11.1 (Ern1 protein, mouse); EC 2.7.11.1 (Protein-Serine-Threonine Kinases); EC 2.7.12.2 (MAP Kinase Kinase 4); EC 3.1.- (Endoribonucleases)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170801
[Lr] Data última revisão:
170801
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161214
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0167979



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