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Pesquisa : D08.811.277.040.330.300.100.102 [Categoria DeCS]
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[PMID]:29024627
[Au] Autor:Deng Z; Luo P; Lai W; Song T; Peng J; Wei HK
[Ad] Endereço:Department of Animal Nutrition and Feed Science, College of Animal Science and Technology, Huazhong Agricultural University, 430070, Wuhan, China; The Cooperative Innovation Center for Sustainable Pig Production, Wuhan, 430070, Hubei, China.
[Ti] Título:Myostatin inhibits eEF2K-eEF2 by regulating AMPK to suppress protein synthesis.
[So] Source:Biochem Biophys Res Commun;494(1-2):278-284, 2017 Dec 09.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Growth of skeletal muscle is dependent on the protein synthesis, and the rate of protein synthesis is mainly regulated in the stage of translation initiation and elongation. Myostatin, a member of the transforming growth factor-ß (TGF-ß) superfamily, is a negative regulator of protein synthesis. C2C12 myotubes was incubated with 0, 0.01, 0.1, 1, 2, 3 µg/mL myostatin recombinant protein, and then we detected the rates of protein synthesis by the method of SUnSET. We found that high concentrations of myostatin (2 and 3 µg/mL) inhibited protein synthesis by blocking mTOR and eEF2K-eEF2 pathway, while low concentration of myostatin (0.01, 0.1 and 1 µg/mL) regulated eEF2K-eEF2 pathway activity to block protein synthesis without affected mTOR pathway, and myostatin inhibited eEF2K-eEF2 pathway through regulating AMPK pathway to suppress protein synthesis. It provided a new mechanism for myostatin regulating protein synthesis and treating muscle atrophy.
[Mh] Termos MeSH primário: Proteínas Quinases Ativadas por AMP/genética
Quinase do Fator 2 de Elongação/antagonistas & inibidores
Mioblastos/efeitos dos fármacos
Miostatina/farmacologia
Fator 2 de Elongação de Peptídeos/antagonistas & inibidores
Biossíntese de Proteínas/efeitos dos fármacos
[Mh] Termos MeSH secundário: Proteínas Quinases Ativadas por AMP/metabolismo
Animais
Linhagem Celular Transformada
Relação Dose-Resposta a Droga
Quinase do Fator 2 de Elongação/genética
Quinase do Fator 2 de Elongação/metabolismo
Regulação da Expressão Gênica
Camundongos
Desenvolvimento Muscular/genética
Mioblastos/citologia
Mioblastos/metabolismo
Miostatina/genética
Miostatina/metabolismo
Fator 2 de Elongação de Peptídeos/genética
Fator 2 de Elongação de Peptídeos/metabolismo
Transdução de Sinais
Serina-Treonina Quinases TOR/genética
Serina-Treonina Quinases TOR/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Mstn protein, mouse); 0 (Myostatin); 0 (Peptide Elongation Factor 2); EC 2.7.1.1 (TOR Serine-Threonine Kinases); EC 2.7.1.1 (mTOR protein, mouse); EC 2.7.11.20 (Eef2k protein, mouse); EC 2.7.11.20 (Elongation Factor 2 Kinase); EC 2.7.11.31 (AMP-Activated Protein Kinases)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171013
[St] Status:MEDLINE


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[PMID]:28345161
[Au] Autor:McCamphill PK; Ferguson L; Sossin WS
[Ad] Endereço:Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada.
[Ti] Título:A decrease in eukaryotic elongation factor 2 phosphorylation is required for local translation of sensorin and long-term facilitation in Aplysia.
[So] Source:J Neurochem;142(2):246-259, 2017 Jul.
[Is] ISSN:1471-4159
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Mechanistic target of rapamycin complex 1 (mTORC1)-dependent protein synthesis is required for many forms of synaptic plasticity and memory, but the downstream pathways important for synaptic plasticity are poorly understood. Long-term facilitation (LTF) in Aplysia is a form of synaptic plasticity that is closely linked to behavioral memory and an attractive model system for examining the important downstream targets for mTORC1 in regulating synaptic plasticity. Although mTORC1-regulated protein synthesis has been strongly linked to translation initiation, translation elongation is also regulated by mTORC1 and LTF leads to an mTORC1-dependent decrease in eukaryotic elongation factor 2 (eEF2) phosphorylation. The purpose of this study is to test the hypothesis that the decrease in eEF2 phosphorylation is required for mTORC1-dependent translation and plasticity. We show that the LTF-induced decrease in eEF2 phosphorylation is blocked by expression of an eEF2 kinase (eEF2K) modified to be resistant to mTORC1 regulation. We found that expression of this modified kinase blocked LTF. LTF requires local protein synthesis of the neuropeptide sensorin and importantly, local sensorin synthesis can be measured using a dendra fluorescent protein containing the 5' and 3' untranslated regions (UTRs) of sensorin. Using this construct, we show that blocking eEF2 dephosphorylation also blocks the increase in local sensorin synthesis. These results identify decreases in eEF2 phosphorylation as a critical downstream effector of mTOR required for long-term plasticity and identify an important translational target regulated by decreases in eEF2 phosphorylation.
[Mh] Termos MeSH primário: Quinase do Fator 2 de Elongação/metabolismo
Eucariotos/metabolismo
Potenciação de Longa Duração/fisiologia
Fator 2 de Elongação de Peptídeos/metabolismo
[Mh] Termos MeSH secundário: Animais
Aplysia
Células Cultivadas
Quinase do Fator 2 de Elongação/genética
Neuropeptídeos/metabolismo
Fosforilação
Transdução de Sinais/fisiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Neuropeptides); 0 (Peptide Elongation Factor 2); EC 2.7.11.20 (Elongation Factor 2 Kinase)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170810
[Lr] Data última revisão:
170810
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170328
[St] Status:MEDLINE
[do] DOI:10.1111/jnc.14030


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[PMID]:28180304
[Au] Autor:Mikhailova T; Shuvalova E; Ivanov A; Susorov D; Shuvalov A; Kolosov PM; Alkalaeva E
[Ad] Endereço:Engelhardt Institute of Molecular Biology, The Russian Academy of Sciences, Moscow, Russia.
[Ti] Título:RNA helicase DDX19 stabilizes ribosomal elongation and termination complexes.
[So] Source:Nucleic Acids Res;45(3):1307-1318, 2017 02 17.
[Is] ISSN:1362-4962
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The human DEAD-box RNA-helicase DDX19 functions in mRNA export through the nuclear pore complex. The yeast homolog of this protein, Dbp5, has been reported to participate in translation termination. Using a reconstituted mammalian in vitro translation system, we show that the human protein DDX19 is also important for translation termination. It is associated with the fraction of translating ribosomes. We show that DDX19 interacts with pre-termination complexes (preTCs) in a nucleotide-dependent manner. Furthermore, DDX19 increases the efficiency of termination complex (TC) formation and the peptide release in the presence of eukaryotic release factors. Using the eRF1(AGQ) mutant protein or a non-hydrolysable analog of GTP to inhibit subsequent peptidyl-tRNA hydrolysis, we reveal that the activation of translation termination by DDX19 occurs during the stop codon recognition. This activation is a result of DDX19 binding to preTC and a concomitant stabilization of terminating ribosomes. Moreover, we show that DDX19 stabilizes ribosome complexes with translation elongation factors eEF1 and eEF2. Taken together, our findings reveal that the human RNA helicase DDX19 actively participates in protein biosynthesis.
[Mh] Termos MeSH primário: RNA Helicases DEAD-box/metabolismo
Proteínas de Transporte Nucleocitoplasmático/metabolismo
Elongação Traducional da Cadeia Peptídica/fisiologia
Terminação Traducional da Cadeia Peptídica/fisiologia
Ribossomos/metabolismo
[Mh] Termos MeSH secundário: Códon de Terminação
RNA Helicases DEAD-box/genética
Células HEK293
Seres Humanos
Mutação
Proteínas de Transporte Nucleocitoplasmático/genética
Fator 1 de Elongação de Peptídeos/metabolismo
Fator 2 de Elongação de Peptídeos/metabolismo
Polirribossomos/metabolismo
Aminoacil-RNA de Transferência/metabolismo
Proteínas de Saccharomyces cerevisiae/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Codon, Terminator); 0 (Nucleocytoplasmic Transport Proteins); 0 (Peptide Elongation Factor 1); 0 (Peptide Elongation Factor 2); 0 (RNA, Transfer, Amino Acyl); 0 (Saccharomyces cerevisiae Proteins); 0 (tRNA, peptidyl-); EC 3.6.1.- (DBP5 protein, S cerevisiae); EC 3.6.1.- (DDX19B protein, human); EC 3.6.4.13 (DEAD-box RNA Helicases)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171003
[Lr] Data última revisão:
171003
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170210
[St] Status:MEDLINE
[do] DOI:10.1093/nar/gkw1239


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[PMID]:28042029
[Au] Autor:Honda T; Imai H; Suzuki T; Miyoshi T; Ito K; Uchiumi T
[Ad] Endereço:Department of Biology, Faculty of Science, Niigata University, Niigata, 950-2181, Japan.
[Ti] Título:Binding of translation elongation factors to individual copies of the archaeal ribosomal stalk protein aP1 assembled onto aP0.
[So] Source:Biochem Biophys Res Commun;483(1):153-158, 2017 Jan 29.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Ribosomes in all organisms contain oligomeric and flexible proteins called stalks, which are responsible for the recruitment of translational GTPase factors to the ribosome. Archaeal ribosomes have three stalk homodimers (aP1) that constitute a heptameric complex with the anchor protein aP0. We investigated the factor binding ability of aP1 proteins assembled onto aP0, by gel-retardation assays. The isolated aP0(aP1) (aP1) (aP1) complex, as well as the form bound to the Escherichia coli 50S core, as a hybrid 50S particle, interacted strongly with elongation factor aEF2, but weakly with aEF1A. These interactions were disrupted by a point mutation, F107S, at the C-terminus of aP1. To examine the ability of each copy of aP0-associated aP1 to bind to elongation factors, we constructed aP0·aP1 variant trimers, composed of an aP0 mutant and a single (aP1) dimer. Biochemical and quantitative analyses revealed that the resultant three trimers, aP0(aP1) , aP0(aP1) , and aP0(aP1) , individually bound two molecules of aEF2, suggesting that each copy of the aP1 C-terminal region in the aP0·aP1 trimers can bind tightly to aEF2. Interestingly, the unstable binding of aEF1A to each of the three aP0·aP1 trimers was remarkably stabilized in the presence of aEF2. The stability of the aEF1A binding to the stalk complex may be affected by the presence of aEF2 bound to the complex, by an unknown mechanism.
[Mh] Termos MeSH primário: Proteínas Arqueais/metabolismo
Fator 2 de Elongação de Peptídeos/metabolismo
Proteínas Ribossômicas/metabolismo
[Mh] Termos MeSH secundário: Proteínas Arqueais/química
Proteínas Arqueais/genética
Mutação
Fator 1 de Elongação de Peptídeos/química
Fator 1 de Elongação de Peptídeos/genética
Fator 1 de Elongação de Peptídeos/metabolismo
Fator 2 de Elongação de Peptídeos/química
Fator 2 de Elongação de Peptídeos/genética
Multimerização Proteica
Pyrococcus horikoshii/metabolismo
Proteínas Ribossômicas/química
Proteínas Ribossômicas/genética
Ribossomos/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Archaeal Proteins); 0 (Peptide Elongation Factor 1); 0 (Peptide Elongation Factor 2); 0 (Ribosomal Proteins)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170601
[Lr] Data última revisão:
170601
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170103
[St] Status:MEDLINE


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[PMID]:27401398
[Au] Autor:Zhang C; Liu X; Zhang C; Li J; Guo W; Yan D; Yang C; Zhao J; Wu X; Shi J
[Ad] Endereço:Department of Cardiology, Affiliated Hospital of Nantong University, Nantong, PR China; Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College, Nantong University, Nantong, Jiangsu, PR China.
[Ti] Título:Phosphorylated eEF2 is SUMOylated and induces cardiomyocyte apoptosis during myocardial ischemia reperfusion.
[So] Source:J Cardiol;69(4):689-698, 2017 Apr.
[Is] ISSN:1876-4738
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Cardiomyocyte apoptosis after myocardial ischemia reperfusion (MIR) blocks the recovery of cardiac function during revascularization treatment. Protein synthesis mediated by eukaryotic elongation factor 2 (eEF2) is vital for the recovery of MIR. eEF2 promotes peptide elongation without phosphorylation of itself. However, the exact function of eEF2 during MIR is unknown. METHODS: We used suture tie-down of left coronary artery (LCA) to induce MIR in vivo, which was confirmed by electrocardiography and Evan's blue/triphenyltetrazolium chloride double staining. Hypoxia/reoxygenation (H/R) treatment was utilized to stimulate H9c2 cells, which was detected by CCK8 assay to evaluate cell viability. eEF2, phosphorylated eEF2, SUMO, Bax, and Bcl-2 protein expressions and location of eEF2 and phosphorylated eEF2 were determined by western blot, immunocytochemistry and immunofluorescent staining. H9c2 cell apoptosis was assessed by flow cytometry. The effects of eEF2 full-length plasmid and its fragments on H9c2 cells were also detected. RESULTS: In vivo, phosphorylated eEF2 to eEF2 ratio decreased gently in rat MIR model. Immunocytochemistry showed that phosphorylated eEF2 translocated to the nucleus of cardiomyocytes during myocardial reperfusion. Furthermore, double immunofluorescent staining in H9c2 cells after H/R treatment also showed phosphorylated eEF2 translocated to the nucleus. Meanwhile, SUMOylation of eEF2 was detected. The overexpression of eEF2 upregulated Bcl-2 expression after H/R treatment, suggesting that eEF2 might reduce cardiomyocyte apoptosis during MIR. In addition, the N-terminal fragment of eEF2 transfection could promote apoptosis. CONCLUSIONS: eEF2 plays a bidirectional role in regulating cardiomyocyte apoptosis during MIR, in which eEF2 can be SUMOylated and translocate into nucleus of cardiomyocytes to promote cardiomyocyte apoptosis when eEF2 is phosphorylated.
[Mh] Termos MeSH primário: Apoptose
Reperfusão Miocárdica
Miócitos Cardíacos/patologia
Sumoilação
[Mh] Termos MeSH secundário: Animais
Modelos Animais de Doenças
Masculino
Fator 2 de Elongação de Peptídeos/metabolismo
Fosforilação
Proteínas Proto-Oncogênicas c-bcl-2/metabolismo
Ratos Sprague-Dawley
Proteína X Associada a bcl-2/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Bax protein, rat); 0 (Peptide Elongation Factor 2); 0 (Proto-Oncogene Proteins c-bcl-2); 0 (bcl-2-Associated X Protein)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170609
[Lr] Data última revisão:
170609
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160713
[St] Status:MEDLINE


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[PMID]:28064318
[Au] Autor:Zolotarev NA; Maksimenko OG; Shidlovskii YV; Georgiev PG; Bonchuk AN
[Ad] Endereço:Institute of Gene Biology, Russian Academy of Sciences, Moscow, 119334 Russia.
[Ti] Título:[Translation elongation factor EF1α1 interacts with ZAD domains of transcription factors from Drosophila melanogaster].
[So] Source:Mol Biol (Mosk);50(6):1014-1019, 2016 Nov-Dec.
[Is] ISSN:0026-8984
[Cp] País de publicação:Russia (Federation)
[La] Idioma:rus
[Ab] Resumo:A large class of arthropod transcription factors is formed by proteins with a characteristic N-terminal Zinc-finger-Associated Domain (ZAD) which contains four cysteine residues that coordinate a zinc ion. The number of putative proteins with ZAD in the Drosophila genome exceeds 90, and the degree of sequence similarity between these domains can be as low as 23%. Efficient binding of ZADs from the proteins Grau, ZIPIC, and Zw5 to the translation elongation factor EF1α1 in nuclear and cytoplasmic extracts has been demonstrated. EF1α1 is probably involved in the regulation of the activity of ZAD-containing transcription factors.
[Mh] Termos MeSH primário: Núcleo Celular/metabolismo
Citoplasma/metabolismo
Proteínas de Ligação a DNA/metabolismo
Proteínas de Drosophila/metabolismo
Fator 2 de Elongação de Peptídeos/metabolismo
Fatores de Transcrição/metabolismo
[Mh] Termos MeSH secundário: Animais
Núcleo Celular/genética
Citoplasma/genética
Proteínas de Ligação a DNA/genética
Proteínas de Drosophila/genética
Drosophila melanogaster
Fator 2 de Elongação de Peptídeos/genética
Domínios Proteicos
Fatores de Transcrição/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (DNA-Binding Proteins); 0 (Drosophila Proteins); 0 (Peptide Elongation Factor 2); 0 (Transcription Factors); 0 (dwg protein, Drosophila); 0 (grau protein, Drosophila)
[Em] Mês de entrada:1703
[Cu] Atualização por classe:170321
[Lr] Data última revisão:
170321
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170109
[St] Status:MEDLINE
[do] DOI:10.7868/S0026898416060252


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[PMID]:28035954
[Au] Autor:Al-Jazzar A; Javaheri B; Prideaux M; Boyde A; Scudamore CL; Cherifi C; Hay E; Hopkinson M; Boyd M; Cohen-Solal M; Farquharson C; Pitsillides AA
[Ad] Endereço:Skeletal Biology Group, Comparative Biomedical Sciences, Royal Veterinary College, Royal College Street, London NW1 0TU, UK. aaljazzar@rvc.ac.uk.
[Ti] Título:Dmp1 Promoter-Driven Diphtheria Toxin Receptor Transgene Expression Directs Unforeseen Effects in Multiple Tissues.
[So] Source:Int J Mol Sci;18(1), 2016 Dec 26.
[Is] ISSN:1422-0067
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:Mice harbouring a dentin matrix protein 1 ( ) promoter-driven human diphtheria toxin (DT) receptor ( ) transgene (Tg) have recently been used to attain targeted ablation of osteocytes by diphtheria toxin (DT) treatment in order to define osteocyte function. Use of these Tg mice has asserted mechano- and novel paracrine regulatory osteocyte functions. To explore osteocyte roles fully, we sought to confirm the selectivity of DT effects in these transgenic mice. However, our findings revealed incomplete DT-induced osteocyte ablation, prevalent misexpression, as well as more prominent histopathological DT-induced changes in multiple organs in Tg than in wild-type (WT) littermate mice. Mechanistic evidence for DT action, via prominent regulation of phosphorylation status of elongation factor-2 (EF-2), was also found in many non-skeletal tissues in Tg mice; indicative of direct "off-target" DT action. Finally, very rapid deterioration in health and welfare status in response to DT treatment was observed in these Tg when compared to WT control mice. Together, these data lead us to conclude that alternative models for osteocyte ablation should be sought and caution be exercised when drawing conclusions from experiments using these Tg mice alone.
[Mh] Termos MeSH primário: Proteínas da Matriz Extracelular/genética
Fator de Crescimento Semelhante a EGF de Ligação à Heparina/genética
Transgenes
[Mh] Termos MeSH secundário: Animais
Osso e Ossos/metabolismo
Encéfalo/metabolismo
Toxina Diftérica/toxicidade
Fator de Crescimento Semelhante a EGF de Ligação à Heparina/metabolismo
Seres Humanos
Rim/metabolismo
Camundongos
Miocárdio/metabolismo
Especificidade de Órgãos
Osteócitos/efeitos dos fármacos
Osteócitos/metabolismo
Fator 2 de Elongação de Peptídeos/metabolismo
Regiões Promotoras Genéticas
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Diphtheria Toxin); 0 (Dmp1 protein, mouse); 0 (Extracellular Matrix Proteins); 0 (Heparin-binding EGF-like Growth Factor); 0 (Peptide Elongation Factor 2)
[Em] Mês de entrada:1704
[Cu] Atualização por classe:170922
[Lr] Data última revisão:
170922
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161231
[St] Status:MEDLINE


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[PMID]:27964761
[Au] Autor:Moreira DS; Murta SM
[Ad] Endereço:Centro de Pesquisas René Rachou CPqRR, Fundação Oswaldo Cruz - FIOCRUZ, Avenida Augusto de Lima 1715, Belo Horizonte, MG, Brazil.
[Ti] Título:Involvement of nucleoside diphosphate kinase b and elongation factor 2 in Leishmania braziliensis antimony resistance phenotype.
[So] Source:Parasit Vectors;9(1):641, 2016 Dec 13.
[Is] ISSN:1756-3305
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Nucleoside diphosphate kinase b (NDKb) is responsible for nucleoside triphosphates synthesis and it has key role in the purine metabolism in trypanosomatid protozoans. Elongation factor 2 (EF2) is an important factor for protein synthesis. Recently, our phosphoproteomic analysis demonstrated that NDKb and EF2 proteins were phosphorylated and dephosphorylated in antimony (Sb )-resistant L. braziliensis line compared to its Sb -susceptible pair, respectively. METHODS: In this study, the overexpression of NDKb and EF2 genes in L. braziliensis and L. infantum was performed to investigate the contribution of these proteins in the Sb -resistance phenotype. Furthermore, we examined the role of lamivudine on Sb susceptibility in clones that overexpress the NDKb gene, and the effect of EF2 kinase (EF2K) inhibitor on the growth of EF2-overexpressing parasites. RESULTS: Western blot analysis demonstrated that NDKb and EF2 proteins are more and less expressed, respectively, in Sb -resistant line of L. braziliensis than its wild-type (WTS) counterpart, corroborating our previous phosphoproteomic data. NDKb or EF2-overexpressing L. braziliensis lines were 1.6 to 2.1-fold more resistant to Sb than the untransfected WTS line. In contrast, no difference in Sb susceptibility was observed in L. infantum parasites overexpressing NDKb or EF2. Susceptibility assays showed that NDKb-overexpressing L. braziliensis lines presented elevated resistance to lamivudine, an antiviral agent, but it did not alter the leishmanicidal activity in association with Sb . EF2-overexpressing L. braziliensis clone was slightly more resistant to EF2K inhibitor than the WTS line. Surprisingly, this inhibitor increased the antileishmanial effect of Sb , suggesting that this association might be a valuable strategy for leishmaniasis chemotherapy. CONCLUSION: Our findings represent the first study of NDKb and EF2 genes overexpression that demonstrates an increase of Sb resistance in L. braziliensis which can contribute to develop new strategies for leishmaniasis treatment.
[Mh] Termos MeSH primário: Antimônio/toxicidade
Resistência a Medicamentos
Leishmania braziliensis/efeitos dos fármacos
Leishmania braziliensis/genética
Nucleosídeo NM23 Difosfato Quinases/análise
Fator 2 de Elongação de Peptídeos/análise
[Mh] Termos MeSH secundário: Western Blotting
Perfilação da Expressão Gênica
Leishmania infantum/efeitos dos fármacos
Leishmania infantum/genética
Nucleosídeo NM23 Difosfato Quinases/genética
Fator 2 de Elongação de Peptídeos/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (NM23 Nucleoside Diphosphate Kinases); 0 (Peptide Elongation Factor 2); 9IT35J3UV3 (Antimony)
[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:161215
[St] Status:MEDLINE


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[PMID]:27572820
[Au] Autor:De Gassart A; Demaria O; Panes R; Zaffalon L; Ryazanov AG; Gilliet M; Martinon F
[Ad] Endereço:Department of Biochemistry, University of Lausanne, Epalinges, Switzerland.
[Ti] Título:Pharmacological eEF2K activation promotes cell death and inhibits cancer progression.
[So] Source:EMBO Rep;17(10):1471-1484, 2016 Oct.
[Is] ISSN:1469-3178
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Activation of the elongation factor 2 kinase (eEF2K) leads to the phosphorylation and inhibition of the elongation factor eEF2, reducing mRNA translation rates. Emerging evidence indicates that the regulation of factors involved in protein synthesis may be critical for controlling diverse biological processes including cancer progression. Here we show that inhibitors of the HIV aspartyl protease (HIV-PIs), nelfinavir in particular, trigger a robust activation of eEF2K leading to the phosphorylation of eEF2. Beyond its anti-viral effects, nelfinavir has antitumoral activity and promotes cell death. We show that nelfinavir-resistant cells specifically evade eEF2 inhibition. Decreased cell viability induced by nelfinavir is impaired in cells lacking eEF2K. Moreover, nelfinavir-mediated anti-tumoral activity is severely compromised in eEF2K-deficient engrafted tumors in vivo Our findings imply that exacerbated activation of eEF2K is detrimental for tumor survival and describe a mechanism explaining the anti-tumoral properties of HIV-PIs.
[Mh] Termos MeSH primário: Quinase do Fator 2 de Elongação/metabolismo
Neoplasias/metabolismo
Neoplasias/patologia
[Mh] Termos MeSH secundário: Proteínas Quinases Ativadas por AMP/metabolismo
Animais
Morte Celular/efeitos dos fármacos
Morte Celular/genética
Linhagem Celular
Sobrevivência Celular/efeitos dos fármacos
Sobrevivência Celular/genética
Modelos Animais de Doenças
Progressão da Doença
Relação Dose-Resposta a Droga
Resistência a Medicamentos/genética
Quinase do Fator 2 de Elongação/genética
Feminino
Expressão Gênica
Seres Humanos
Alvo Mecanístico do Complexo 1 de Rapamicina
Camundongos
Camundongos Knockout
Complexos Multiproteicos/metabolismo
Nelfinavir/química
Nelfinavir/farmacologia
Neoplasias/genética
Fator 2 de Elongação de Peptídeos/metabolismo
Fosforilação
Biossíntese de Proteínas
Serina-Treonina Quinases TOR/metabolismo
Carga Tumoral
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Multiprotein Complexes); 0 (Peptide Elongation Factor 2); EC 2.7.1.1 (TOR Serine-Threonine Kinases); EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 1); EC 2.7.11.20 (Eef2k protein, mouse); EC 2.7.11.20 (Elongation Factor 2 Kinase); EC 2.7.11.31 (AMP-Activated Protein Kinases); HO3OGH5D7I (Nelfinavir)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160831
[St] Status:MEDLINE


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[PMID]:27572728
[Au] Autor:Grigorieff N
[Ad] Endereço:Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, United States. Electronic address: niko@grigorieff.org.
[Ti] Título:Frealign: An Exploratory Tool for Single-Particle Cryo-EM.
[So] Source:Methods Enzymol;579:191-226, 2016.
[Is] ISSN:1557-7988
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Frealign is a software tool designed to process electron microscope images of single molecules and complexes to obtain reconstructions at the highest possible resolution. It provides a number of refinement parameters and options that allow users to tune their refinement to achieve specific goals, such as masking to classify selected regions within a particle, control over the refinement of specific alignment parameters to accommodate various data collection schemes, refinement of pseudosymmetric particles, and generation of initial maps. This chapter provides a general overview of Frealign functions and a more detailed guide to using Frealign in typical scenarios.
[Mh] Termos MeSH primário: Algoritmos
Microscopia Crioeletrônica/métodos
Processamento de Imagem Assistida por Computador/estatística & dados numéricos
Imagem Individual de Molécula/métodos
Software
[Mh] Termos MeSH secundário: Microscopia Crioeletrônica/instrumentação
Processamento de Imagem Assistida por Computador/métodos
Imagem Tridimensional/instrumentação
Imagem Tridimensional/métodos
Modelos Moleculares
Fator 2 de Elongação de Peptídeos/ultraestrutura
Ribossomos/ultraestrutura
Imagem Individual de Molécula/estatística & dados numéricos
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Peptide Elongation Factor 2)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170811
[Lr] Data última revisão:
170811
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160831
[St] Status:MEDLINE



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