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[PMID]:28456966
[Au] Autor:Uh K; Lee K
[Ad] Endereço:Department of Animal and Poultry Sciences, Virginia Tech, Blacksburg, VA, USA.
[Ti] Título:Use of Chemicals to Inhibit DNA Replication, Transcription, and Protein Synthesis to Study Zygotic Genome Activation.
[So] Source:Methods Mol Biol;1605:191-205, 2017.
[Is] ISSN:1940-6029
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Maternal-to-zygotic transition is an event that developmental control of early embryos is switched from oocyte-derived factors to the zygotic genome. Ability to inhibit DNA replication, transcription, and translation is an important tool in studying events, such as zygotic genome activation, during embyogenesis. Here, we describe approaches to block DNA replication, transcription, and translation using chemical inhibitors. Then we also demonstrate how the transcript level of a maternally inherited gene, ten-eleven translocation methylcytosine dioxygenase 3, responses to the chemical treatments.
[Mh] Termos MeSH primário: Alfa-Amanitina/farmacologia
Cicloeximida/farmacologia
Inibidores da Síntese de Ácido Nucleico/farmacologia
Inibidores da Síntese de Proteínas/farmacologia
Suínos/embriologia
[Mh] Termos MeSH secundário: Animais
Metilação de DNA
Replicação do DNA/efeitos dos fármacos
Dioxigenases/genética
Herança Materna
Biossíntese de Proteínas/efeitos dos fármacos
Suínos/genética
Transcrição Genética/efeitos dos fármacos
Ativação Transcricional
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Alpha-Amanitin); 0 (Nucleic Acid Synthesis Inhibitors); 0 (Protein Synthesis Inhibitors); 98600C0908 (Cycloheximide); EC 1.13.11.- (Dioxygenases)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180212
[Lr] Data última revisão:
180212
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170501
[St] Status:MEDLINE
[do] DOI:10.1007/978-1-4939-6988-3_13


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[PMID]:28468971
[Au] Autor:Olson MR; Ulrich BJ; Hummel SA; Khan I; Meuris B; Cherukuri Y; Dent AL; Janga SC; Kaplan MH
[Ad] Endereço:Department of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202; olsonmr@iupui.edu mkaplan2@iupui.edu.
[Ti] Título:Paracrine IL-2 Is Required for Optimal Type 2 Effector Cytokine Production.
[So] Source:J Immunol;198(11):4352-4359, 2017 06 01.
[Is] ISSN:1550-6606
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:IL-2 is a pleiotropic cytokine that promotes the differentiation of Th cell subsets, including Th1, Th2, and Th9 cells, but it impairs the development of Th17 and T follicular helper cells. Although IL-2 is produced by all polarized Th subsets to some level, how it impacts cytokine production when effector T cells are restimulated is unknown. We show in this article that Golgi transport inhibitors (GTIs) blocked IL-9 production. Mechanistically, GTIs blocked secretion of IL-2 that normally feeds back in a paracrine manner to promote STAT5 activation and IL-9 production. IL-2 feedback had no effect on Th1- or Th17-signature cytokine production, but it promoted Th2- and Th9-associated cytokine expression. These data suggest that the use of GTIs results in an underestimation of the presence of type 2 cytokine-secreting cells and highlight IL-2 as a critical component in optimal cytokine production by Th2 and Th9 cells in vitro and in vivo.
[Mh] Termos MeSH primário: Citocinas/biossíntese
Interleucina-2/metabolismo
Interleucina-9/biossíntese
Comunicação Parácrina
Células Th2/imunologia
[Mh] Termos MeSH secundário: Animais
Brefeldina A/farmacologia
Diferenciação Celular
Citocinas/imunologia
Interleucina-2/secreção
Interleucina-9/antagonistas & inibidores
Interleucina-9/imunologia
Ativação Linfocitária
Camundongos
Camundongos Endogâmicos C57BL
Monensin/farmacologia
Inibidores da Síntese de Proteínas/farmacologia
Ionóforos de Próton/farmacologia
Fator de Transcrição STAT5/metabolismo
Células Th1/imunologia
Células Th17/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Cytokines); 0 (Interleukin-2); 0 (Interleukin-9); 0 (Protein Synthesis Inhibitors); 0 (Proton Ionophores); 0 (STAT5 Transcription Factor); 20350-15-6 (Brefeldin A); 906O0YJ6ZP (Monensin)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:180127
[Lr] Data última revisão:
180127
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170505
[St] Status:MEDLINE
[do] DOI:10.4049/jimmunol.1601792


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[PMID]:29028794
[Au] Autor:Ward JR; Vasu K; Deutschman E; Halawani D; Larson PA; Zhang D; Willard B; Fox PL; Moran JV; Longworth MS
[Ad] Endereço:Department of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, United States of America.
[Ti] Título:Condensin II and GAIT complexes cooperate to restrict LINE-1 retrotransposition in epithelial cells.
[So] Source:PLoS Genet;13(10):e1007051, 2017 Oct.
[Is] ISSN:1553-7404
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:LINE-1 (L1) retrotransposons can mobilize (retrotranspose) within the human genome, and mutagenic de novo L1 insertions can lead to human diseases, including cancers. As a result, cells are actively engaged in preventing L1 retrotransposition. This work reveals that the human Condensin II complex restricts L1 retrotransposition in both non-transformed and transformed cell lines through inhibition of L1 transcription and translation. Condensin II subunits, CAP-D3 and CAP-H2, interact with members of the Gamma-Interferon Activated Inhibitor of Translation (GAIT) complex including the glutamyl-prolyl-tRNA synthetase (EPRS), the ribosomal protein L13a, Glyceraldehyde 3-phosphate dehydrogenase (GAPDH), and NS1 associated protein 1 (NSAP1). GAIT has been shown to inhibit translation of mRNAs encoding inflammatory proteins in myeloid cells by preventing the binding of the translation initiation complex, in response to Interferon gamma (IFN-γ). Excitingly, our data show that Condensin II promotes complexation of GAIT subunits. Furthermore, RNA-Immunoprecipitation experiments in epithelial cells demonstrate that Condensin II and GAIT subunits associate with L1 RNA in a co-dependent manner, independent of IFN-γ. These findings suggest that cooperation between the Condensin II and GAIT complexes may facilitate a novel mechanism of L1 repression, thus contributing to the maintenance of genome stability in somatic cells.
[Mh] Termos MeSH primário: Proteínas de Ciclo Celular/genética
Interferon gama/genética
Elementos Nucleotídeos Longos e Dispersos/genética
Proteínas Nucleares/genética
[Mh] Termos MeSH secundário: Adenosina Trifosfatases/genética
Proteínas de Ligação a DNA/genética
Células Epiteliais/metabolismo
Genoma Humano
Seres Humanos
Fator Gênico 3 Estimulado por Interferon/genética
Complexos Multiproteicos/genética
Ligação Proteica
Inibidores da Síntese de Proteínas
RNA Mensageiro/genética
Retroelementos/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cell Cycle Proteins); 0 (DNA-Binding Proteins); 0 (Interferon-Stimulated Gene Factor 3); 0 (Multiprotein Complexes); 0 (NCAPH protein, human); 0 (Nuclear Proteins); 0 (Protein Synthesis Inhibitors); 0 (RNA, Messenger); 0 (Retroelements); 0 (chromosome-associated protein D3, human); 0 (condensin complexes); 0 (gamma interferon activation factor); 82115-62-6 (Interferon-gamma); EC 3.6.1.- (Adenosine Triphosphatases)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171110
[Lr] Data última revisão:
171110
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171014
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pgen.1007051


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[PMID]:28977617
[Au] Autor:Yang K; Chang JY; Cui Z; Li X; Meng R; Duan L; Thongchol J; Jakana J; Huwe CM; Sacchettini JC; Zhang J
[Ad] Endereço:Department of Biochemistry and Biophysics, Texas A&M University, College Station, TX 77843, USA.
[Ti] Título:Structural insights into species-specific features of the ribosome from the human pathogen Mycobacterium tuberculosis.
[So] Source:Nucleic Acids Res;45(18):10884-10894, 2017 Oct 13.
[Is] ISSN:1362-4962
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Ribosomes from Mycobacterium tuberculosis (Mtb) possess species-specific ribosomal RNA (rRNA) expansion segments and ribosomal proteins (rProtein). Here, we present the near-atomic structures of the Mtb 50S ribosomal subunit and the complete Mtb 70S ribosome, solved by cryo-electron microscopy. Upon joining of the large and small ribosomal subunits, a 100-nt long expansion segment of the Mtb 23S rRNA, named H54a or the 'handle', switches interactions from with rRNA helix H68 and rProtein uL2 to with rProtein bS6, forming a new intersubunit bridge 'B9'. In Mtb 70S, bridge B9 is mostly maintained, leading to correlated motions among the handle, the L1 stalk and the small subunit in the rotated and non-rotated states. Two new protein densities were discovered near the decoding center and the peptidyl transferase center, respectively. These results provide a structural basis for studying translation in Mtb as well as developing new tuberculosis drugs.
[Mh] Termos MeSH primário: Mycobacterium tuberculosis/química
Ribossomos/química
[Mh] Termos MeSH secundário: Microscopia Crioeletrônica
Modelos Moleculares
Movimento (Física)
Mycobacterium smegmatis/química
Inibidores da Síntese de Proteínas
Proteínas Ribossômicas/química
Subunidades Ribossômicas Maiores de Bactérias/química
Especificidade da Espécie
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Protein Synthesis Inhibitors); 0 (Ribosomal Proteins)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171107
[Lr] Data última revisão:
171107
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171005
[St] Status:MEDLINE
[do] DOI:10.1093/nar/gkx785


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[PMID]:28934499
[Au] Autor:Almutairi MM; Svetlov MS; Hansen DA; Khabibullina NF; Klepacki D; Kang HY; Sherman DH; Vázquez-Laslop N; Polikanov YS; Mankin AS
[Ad] Endereço:Center for Biomolecular Sciences, University of Illinois, Chicago, IL 60607, USA.
[Ti] Título:Co-produced natural ketolides methymycin and pikromycin inhibit bacterial growth by preventing synthesis of a limited number of proteins.
[So] Source:Nucleic Acids Res;45(16):9573-9582, 2017 Sep 19.
[Is] ISSN:1362-4962
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Antibiotics methymycin (MTM) and pikromycin (PKM), co-produced by Streptomyces venezuelae, represent minimalist macrolide protein synthesis inhibitors. Unlike other macrolides, which carry several side chains, a single desosamine sugar is attached to the macrolactone ring of MTM and PKM. In addition, the macrolactone scaffold of MTM is smaller than in other macrolides. The unusual structure of MTM and PKM and their simultaneous secretion by S. venezuelae bring about the possibility that two compounds would bind to distinct ribosomal sites. However, by combining genetic, biochemical and crystallographic studies, we demonstrate that MTM and PKM inhibit translation by binding to overlapping sites in the ribosomal exit tunnel. Strikingly, while MTM and PKM readily arrest the growth of bacteria, ∼40% of cellular proteins continue to be synthesized even at saturating concentrations of the drugs. Gel electrophoretic analysis shows that compared to other ribosomal antibiotics, MTM and PKM prevent synthesis of a smaller number of cellular polypeptides illustrating a unique mode of action of these antibiotics.
[Mh] Termos MeSH primário: Proteínas de Bactérias/biossíntese
Escherichia coli/efeitos dos fármacos
Macrolídeos/farmacologia
Inibidores da Síntese de Proteínas/farmacologia
[Mh] Termos MeSH secundário: Ligação Competitiva
Cristalografia por Raios X
Escherichia coli/genética
Escherichia coli/crescimento & desenvolvimento
Macrolídeos/química
Macrolídeos/metabolismo
Fator G para Elongação de Peptídeos/genética
Ribossomos/química
Ribossomos/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Bacterial Proteins); 0 (Macrolides); 0 (Peptide Elongation Factor G); 0 (Protein Synthesis Inhibitors); 16QGD97DXG (methymycin); FBM8G3Z439 (picromycin)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171024
[Lr] Data última revisão:
171024
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170922
[St] Status:MEDLINE
[do] DOI:10.1093/nar/gkx673


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[PMID]:28822840
[Au] Autor:Chakraborti S; Sarkar J; Chowdhury A; Chakraborti T
[Ad] Endereço:Department of Biochemistry and Biophysics, University of Kalyani, Kalyani 741235, West Bengal, India. Electronic address: sajal_chakraborti@yahoo.com.
[Ti] Título:Role of ADP ribosylation factor6- Cytohesin1-PhospholipaseD signaling axis in U46619 induced activation of NADPH oxidase in pulmonary artery smooth muscle cell membrane.
[So] Source:Arch Biochem Biophys;633:1-14, 2017 Nov 01.
[Is] ISSN:1096-0384
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Treatment of human pulmonary artery smooth muscle cells (HPASMCs) with the thromboxane A2 receptor antagonist, SQ29548 inhibited U46619 stimulation of phospholipase D (PLD) and NADPH oxidase activities in the cell membrane. Pretreatment with apocynin inhibited U46619 induced increase in NADPH oxidase activity. The cell membrane contains predominantly PLD2 along with PLD1 isoforms of PLD. Pretreatment with pharmacological and genetic inhibitors of PLD2, but not PLD1, attenuated U46619 stimulation of NADPH oxidase activity. U46619 stimulation of PLD and NADPH oxidase activities were insensitive to BFA and Clostridium botulinum C3 toxin; however, pretreatment with secinH3 inhibited U46619 induced increase in PLD and NADPH oxidase activities suggesting a major role of cytohesin in U46619-induced increase in PLD and NADPH oxidase activities. Arf-1, Arf-6, cytohesin-1 and cytohesin-2 were observed in the cytosolic fraction, but only Arf-6 and cytohesin-1 were translocated to the cell membrane upon treatment with U46619. Coimmunoprecipitation study showed association of Arf-6 with cytohesin-1 in the cell membrane fraction. In vitro binding of GTPγS with Arf-6 required the presence of cytohesin-1 and that occurs in BFA insensitive manner. Overall, BFA insensitive Arf6-cytohesin1 signaling axis plays a pivotal role in U46619-mediated activation of PLD leading to stimulation of NADPH oxidase activity in HPASMCs.
[Mh] Termos MeSH primário: Ácido 15-Hidroxi-11 alfa,9 alfa-(epoximetano)prosta-5,13-dienoico/farmacologia
Fatores de Ribosilação do ADP/genética
Fatores de Troca do Nucleotídeo Guanina/genética
NADPH Oxidases/genética
Fosfolipase D/genética
Vasoconstritores/farmacologia
[Mh] Termos MeSH secundário: ADP Ribose Transferases/farmacologia
Fatores de Ribosilação do ADP/metabolismo
Acetofenonas/farmacologia
Antioxidantes/farmacologia
Toxinas Botulínicas/farmacologia
Brefeldina A/farmacologia
Membrana Celular/efeitos dos fármacos
Membrana Celular/metabolismo
Proteínas Ativadoras de GTPase/antagonistas & inibidores
Proteínas Ativadoras de GTPase/genética
Proteínas Ativadoras de GTPase/metabolismo
Regulação da Expressão Gênica
Fatores de Troca do Nucleotídeo Guanina/antagonistas & inibidores
Fatores de Troca do Nucleotídeo Guanina/metabolismo
Guanosina 5'-O-(3-Tiotrifosfato)/farmacologia
Seres Humanos
Hidrazinas/farmacologia
Miócitos de Músculo Liso/citologia
Miócitos de Músculo Liso/efeitos dos fármacos
Miócitos de Músculo Liso/metabolismo
NADPH Oxidases/metabolismo
Fosfolipase D/antagonistas & inibidores
Fosfolipase D/metabolismo
Cultura Primária de Células
Inibidores da Síntese de Proteínas/farmacologia
Artéria Pulmonar/citologia
Artéria Pulmonar/efeitos dos fármacos
Artéria Pulmonar/metabolismo
Receptores de Tromboxano A2 e Prostaglandina H2/antagonistas & inibidores
Receptores de Tromboxano A2 e Prostaglandina H2/genética
Receptores de Tromboxano A2 e Prostaglandina H2/metabolismo
Transdução de Sinais
Triazóis/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Acetophenones); 0 (Antioxidants); 0 (GTPase-Activating Proteins); 0 (Guanine Nucleotide Exchange Factors); 0 (Hydrazines); 0 (Protein Synthesis Inhibitors); 0 (Receptors, Thromboxane A2, Prostaglandin H2); 0 (SecinH3); 0 (Triazoles); 0 (Vasoconstrictor Agents); 0 (cytohesin-1); 0 (cytohesin-2); 20350-15-6 (Brefeldin A); 37589-80-3 (Guanosine 5'-O-(3-Thiotriphosphate)); 76898-47-0 (15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid); 98299-61-7 (SQ 29548); B6J7B9UDTR (acetovanillone); EC 1.6.3.- (NADPH Oxidases); EC 2.4.2.- (ADP Ribose Transferases); EC 2.4.2.- (exoenzyme C3, Clostridium botulinum); EC 3.1.4.- (phospholipase D2); EC 3.1.4.4 (Phospholipase D); EC 3.1.4.4 (phospholipase D1); EC 3.4.24.69 (Botulinum Toxins); EC 3.6.5.2 (ADP-Ribosylation Factors); EC 3.6.5.2 (ADP-ribosylation factor 6)
[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:170821
[St] Status:MEDLINE


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[PMID]:28821580
[Au] Autor:Marques-Ramos A; Candeias MM; Menezes J; Lacerda R; Willcocks M; Teixeira A; Locker N; Romão L
[Ad] Endereço:Departamento de Genética Humana, Instituto Nacional de Saúde Doutor Ricardo Jorge, 1649-016 Lisboa, Portugal.
[Ti] Título:Cap-independent translation ensures mTOR expression and function upon protein synthesis inhibition.
[So] Source:RNA;23(11):1712-1728, 2017 Nov.
[Is] ISSN:1469-9001
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The mechanistic/mammalian target of rapamycin (mTOR) is a conserved serine/threonine kinase that integrates cellular signals from the nutrient and energy status to act, namely, on the protein synthesis machinery. While major advances have emerged regarding the regulators and effects of the mTOR signaling pathway, little is known about the regulation of gene expression. Here, we show that the human transcript can be translated in a cap-independent manner, and that its 5' untranslated region (UTR) is a highly folded RNA scaffold capable of binding directly to the 40S ribosomal subunit. We further demonstrate that is able to bypass the cap requirement for translation both in normal and hypoxic conditions. Moreover, our data reveal that the cap-independent translation of mTOR is necessary for its ability to induce cell-cycle progression into S phase. These results suggest a novel regulatory mechanism for gene expression that integrates the global protein synthesis changes induced by translational inhibitory conditions.
[Mh] Termos MeSH primário: Serina-Treonina Quinases TOR/genética
Serina-Treonina Quinases TOR/metabolismo
[Mh] Termos MeSH secundário: Regiões 5' não Traduzidas
Animais
Hipóxia Celular/genética
Linhagem Celular
Evolução Molecular
Regulação da Expressão Gênica
Células HCT116
Células HEK293
Células HeLa
Seres Humanos
Hidrazonas/farmacologia
Luciferases de Vaga-Lume/genética
Luciferases de Vaga-Lume/metabolismo
Biossíntese de Proteínas
Inibidores da Síntese de Proteínas/farmacologia
Capuzes de RNA/genética
Capuzes de RNA/metabolismo
Dobramento de RNA
RNA Mensageiro/química
RNA Mensageiro/genética
RNA Mensageiro/metabolismo
Pontos de Checagem da Fase S do Ciclo Celular/genética
Tiazóis/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (4EGI-1 compound); 0 (5' Untranslated Regions); 0 (Hydrazones); 0 (Protein Synthesis Inhibitors); 0 (RNA Caps); 0 (RNA, Messenger); 0 (Thiazoles); EC 1.13.12.7 (Luciferases, Firefly); EC 2.7.1.1 (MTOR protein, human); EC 2.7.1.1 (TOR Serine-Threonine Kinases)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171101
[Lr] Data última revisão:
171101
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170820
[St] Status:MEDLINE
[do] DOI:10.1261/rna.063040.117


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[PMID]:28787571
[Au] Autor:Bartolowits MD; Brown W; Ali R; Pedley AM; Chen Q; Harvey KE; Wendt MK; Davisson VJ
[Ad] Endereço:Department of Medicinal Chemistry and Molecular Pharmacology, College of Pharmacy, Purdue University , West Lafayette, Indiana 47907, United States.
[Ti] Título:Selective Inhibition of STAT3 Phosphorylation Using a Nuclear-Targeted Kinase Inhibitor.
[So] Source:ACS Chem Biol;12(9):2371-2378, 2017 Sep 15.
[Is] ISSN:1554-8937
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The discovery of compounds that selectively modulate signaling and effector proteins downstream of EGFR could have important implications for understanding specific roles for pathway activation. A complicating factor for receptor tyrosine kinases is their capacity to be translocated to the nucleus upon ligand engagement. Once localized in subcellular compartments like the nucleus, the roles for EGFR take on additional features, many of which are still being revealed. Additionally, nuclear localization of EGFR has been implicated in downstream events that have significance for therapy resistance and disease progression. The challenges to addressing the differential roles for EGFR in the nucleus motivated experimental approaches that can selectively modulate its subcellular function. By adding modifications to the established EGFR kinase inhibitor gefitinib, an approach to small molecule conjugates with a unique nuclear-targeting peptoid sequence was tested in both human and murine breast tumor cell models for their capacity to inhibit EGF-stimulated activation of ERK1/2 and STAT3. While gefitinib alone inhibits both of these downstream effectors, data acquired here indicate that compartmentalization of the gefitinib conjugates allows for pathway specific inhibition of STAT3 while not affecting ERK1/2 signaling. The inhibitor conjugates offered a more direct route to evaluate the role of EGF-stimulated epithelial-to-mesenchymal transition in these breast cancer cell models. These conjugates revealed that STAT3 activation is not involved in EGF-induced EMT, and instead utilization of the cytoplasmic MAP kinase signaling pathway is critical to this process. This is the first example of a conjugate kinase inhibitor capable of partitioning to the nucleus and offers a new approach to enhancing kinase inhibitor specificity.
[Mh] Termos MeSH primário: Descoberta de Drogas
Fosforilação/efeitos dos fármacos
Inibidores de Proteínas Quinases/farmacologia
Fator de Transcrição STAT3/antagonistas & inibidores
[Mh] Termos MeSH secundário: Neoplasias da Mama/tratamento farmacológico
Neoplasias da Mama/metabolismo
Brefeldina A/farmacologia
Linhagem Celular Tumoral
Sistemas de Liberação de Medicamentos
Transição Epitelial-Mesenquimal/efeitos dos fármacos
Feminino
Seres Humanos
Peptoides/administração & dosagem
Peptoides/química
Peptoides/farmacologia
Inibidores de Proteínas Quinases/administração & dosagem
Inibidores de Proteínas Quinases/química
Inibidores da Síntese de Proteínas/farmacologia
Receptor do Fator de Crescimento Epidérmico/metabolismo
Fator de Transcrição STAT3/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Peptoids); 0 (Protein Kinase Inhibitors); 0 (Protein Synthesis Inhibitors); 0 (STAT3 Transcription Factor); 20350-15-6 (Brefeldin A); EC 2.7.10.1 (Receptor, Epidermal Growth Factor)
[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:170809
[St] Status:MEDLINE
[do] DOI:10.1021/acschembio.7b00341


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[PMID]:28781168
[Au] Autor:Wong HH; Lin JQ; Ströhl F; Roque CG; Cioni JM; Cagnetta R; Turner-Bridger B; Laine RF; Harris WA; Kaminski CF; Holt CE
[Ad] Endereço:Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge CB2 3DY, UK.
[Ti] Título:RNA Docking and Local Translation Regulate Site-Specific Axon Remodeling In Vivo.
[So] Source:Neuron;95(4):852-868.e8, 2017 Aug 16.
[Is] ISSN:1097-4199
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Nascent proteins can be positioned rapidly at precise subcellular locations by local protein synthesis (LPS) to facilitate localized growth responses. Axon arbor architecture, a major determinant of synaptic connectivity, is shaped by localized growth responses, but it is unknown whether LPS influences these responses in vivo. Using high-resolution live imaging, we examined the spatiotemporal dynamics of RNA and LPS in retinal axons during arborization in vivo. Endogenous RNA tracking reveals that RNA granules dock at sites of branch emergence and invade stabilized branches. Live translation reporter analysis reveals that de novo ß-actin hotspots colocalize with docked RNA granules at the bases and tips of new branches. Inhibition of axonal ß-actin mRNA translation disrupts arbor dynamics primarily by reducing new branch emergence and leads to impoverished terminal arbors. The results demonstrate a requirement for LPS in building arbor complexity and suggest a key role for pre-synaptic LPS in assembling neural circuits.
[Mh] Termos MeSH primário: Axônios/fisiologia
Regulação da Expressão Gênica no Desenvolvimento/genética
RNA/metabolismo
[Mh] Termos MeSH secundário: Actinas/genética
Actinas/metabolismo
Animais
Anisomicina/farmacologia
Biotina/metabolismo
Blastômeros
Carbocianinas/metabolismo
Cicloeximida/farmacologia
Nucleotídeos de Desoxiuracil/metabolismo
Embrião não Mamífero
Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos
Técnicas In Vitro
Proteínas Luminescentes/genética
Proteínas Luminescentes/metabolismo
Mitocôndrias/metabolismo
Morfolinos/farmacologia
Oligonucleotídeos Antissenso/farmacologia
Técnicas de Cultura de Órgãos
Inibidores da Síntese de Proteínas/farmacologia
RNA/genética
Retina/citologia
Xenopus laevis
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (3'-deoxy-5-(cyanine dye 5)uridine 5'-trisphosphate); 0 (Actins); 0 (Carbocyanines); 0 (Deoxyuracil Nucleotides); 0 (Luminescent Proteins); 0 (Morpholinos); 0 (Oligonucleotides, Antisense); 0 (Protein Synthesis Inhibitors); 63231-63-0 (RNA); 6C74YM2NGI (Anisomycin); 6SO6U10H04 (Biotin); 98600C0908 (Cycloheximide)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170902
[Lr] Data última revisão:
170902
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170808
[St] Status:MEDLINE


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[PMID]:28771613
[Au] Autor:Anda S; Zach R; Grallert B
[Ad] Endereço:Department of Radiation Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.
[Ti] Título:Activation of Gcn2 in response to different stresses.
[So] Source:PLoS One;12(8):e0182143, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:All organisms have evolved pathways to respond to different forms of cellular stress. The Gcn2 kinase is best known as a regulator of translation initiation in response to starvation for amino acids. Work in budding yeast has showed that the molecular mechanism of GCN2 activation involves the binding of uncharged tRNAs, which results in a conformational change and GCN2 activation. This pathway requires GCN1, which ensures delivery of the uncharged tRNA onto GCN2. However, Gcn2 is activated by a number of other stresses which do not obviously involve accumulation of uncharged tRNAs, raising the question how Gcn2 is activated under these conditions. Here we investigate the requirement for ongoing translation and tRNA binding for Gcn2 activation after different stresses in fission yeast. We find that mutating the tRNA-binding site on Gcn2 or deleting Gcn1 abolishes Gcn2 activation under all the investigated conditions. These results suggest that tRNA binding to Gcn2 is required for Gcn2 activation not only in response to starvation but also after UV irradiation and oxidative stress.
[Mh] Termos MeSH primário: Proteínas Serina-Treonina Quinases/metabolismo
RNA de Transferência/metabolismo
Proteínas de Schizosaccharomyces pombe/metabolismo
Estresse Fisiológico/genética
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Cicloeximida/farmacologia
Fator de Iniciação 2 em Eucariotos/metabolismo
Peróxido de Hidrogênio/toxicidade
Mutagênese
Estresse Oxidativo/efeitos dos fármacos
Fosforilação/efeitos dos fármacos
Fosforilação/efeitos da radiação
Biossíntese de Proteínas/efeitos da radiação
Inibidores da Síntese de Proteínas/farmacologia
Proteínas Serina-Treonina Quinases/química
Proteínas Serina-Treonina Quinases/genética
Schizosaccharomyces/genética
Schizosaccharomyces/metabolismo
Schizosaccharomyces/efeitos da radiação
Proteínas de Schizosaccharomyces pombe/química
Proteínas de Schizosaccharomyces pombe/genética
Alinhamento de Sequência
Raios Ultravioleta
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Eukaryotic Initiation Factor-2); 0 (Protein Synthesis Inhibitors); 0 (Schizosaccharomyces pombe Proteins); 9014-25-9 (RNA, Transfer); 98600C0908 (Cycloheximide); BBX060AN9V (Hydrogen Peroxide); EC 2.7.11.1 (Gcn2 protein, S pombe); EC 2.7.11.1 (Protein-Serine-Threonine Kinases)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171013
[Lr] Data última revisão:
171013
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170804
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0182143



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