Base de dados : MEDLINE
Pesquisa : D08.811.913.696.620.682.700.581 [Categoria DeCS]
Referências encontradas : 363 [refinar]
Mostrando: 1 .. 10   no formato [Detalhado]

página 1 de 37 ir para página                         

  1 / 363 MEDLINE  
              next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29270587
[Au] Autor:Tang X; Wang Z; Lei T; Zhou W; Chang S; Li D
[Ad] Endereço:College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang 310058, P. R. China. lidancps@zju.edu.cn.
[Ti] Título:Importance of protein flexibility on molecular recognition: modeling binding mechanisms of aminopyrazine inhibitors to Nek2.
[So] Source:Phys Chem Chem Phys;20(8):5591-5605, 2018 Feb 21.
[Is] ISSN:1463-9084
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:NIMA-related kinase 2 (Nek2) plays a significant role in cell cycle regulation, and overexpression of Nek2 has been observed in several types of carcinoma, suggesting it is a potential target for cancer therapy. In this study, we attempted to gain more insight into the binding mechanisms of a series of aminopyrazine inhibitors of Nek2 through multiple molecular modeling techniques, including molecular docking, molecular dynamics (MD) simulations and free energy calculations. The simulation results showed that the induced fit docking and ensemble docking based on multiple protein structures yield better predictions than conventional rigid receptor docking, highlighting the importance of incorporating receptor flexibility into the accurate predictions of the binding poses and binding affinities of Nek2 inhibitors. Additionally, we observed that the Molecular Mechanics/Generalized Born Surface Area (MM/GBSA) calculations did not show better performance than the docking scoring to rank the binding affinities of the studied inhibitors, suggesting that MM/GBSA is system-dependent and may not be the best choice for the Nek2 systems. Moreover, the detailed information on protein-ligand binding was characterized by the MM/GBSA free energy decomposition, and a number of derivatives with improved docking scores were designed. It is expected that our study can provide valuable information for the future rational design of novel and potent inhibitors of Nek2.
[Mh] Termos MeSH primário: Quinases Relacionadas a NIMA/antagonistas & inibidores
Inibidores de Proteínas Quinases/farmacologia
Pirazinas/farmacologia
[Mh] Termos MeSH secundário: Seres Humanos
Ligantes
Modelos Moleculares
Estrutura Molecular
Quinases Relacionadas a NIMA/metabolismo
Inibidores de Proteínas Quinases/química
Pirazinas/química
Termodinâmica
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Ligands); 0 (Protein Kinase Inhibitors); 0 (Pyrazines); EC 2.7.11.1 (NEK2 protein, human); EC 2.7.11.1 (NIMA-Related Kinases)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180227
[Lr] Data última revisão:
180227
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171223
[St] Status:MEDLINE
[do] DOI:10.1039/c7cp07588j


  2 / 363 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28737508
[Au] Autor:Wang J; Cheng P; Pavlyukov MS; Yu H; Zhang Z; Kim SH; Minata M; Mohyeldin A; Xie W; Chen D; Goidts V; Frett B; Hu W; Li H; Shin YJ; Lee Y; Nam DH; Kornblum HI; Wang M; Nakano I
[Ad] Endereço:Department of Neurosurgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
[Ti] Título:Targeting NEK2 attenuates glioblastoma growth and radioresistance by destabilizing histone methyltransferase EZH2.
[So] Source:J Clin Invest;127(8):3075-3089, 2017 Aug 01.
[Is] ISSN:1558-8238
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Accumulating evidence suggests that glioma stem cells (GSCs) are important therapeutic targets in glioblastoma (GBM). In this study, we identified NIMA-related kinase 2 (NEK2) as a functional binding protein of enhancer of zeste homolog 2 (EZH2) that plays a critical role in the posttranslational regulation of EZH2 protein in GSCs. NEK2 was among the most differentially expressed kinase-encoding genes in GSC-containing cultures (glioma spheres), and it was required for in vitro clonogenicity, in vivo tumor propagation, and radioresistance. Mechanistically, the formation of a protein complex comprising NEK2 and EZH2 in glioma spheres phosphorylated and then protected EZH2 from ubiquitination-dependent protein degradation in a NEK2 kinase activity-dependent manner. Clinically, NEK2 expression in patients with glioma was closely associated with EZH2 expression and correlated with a poor prognosis. NEK2 expression was also substantially elevated in recurrent tumors after therapeutic failure compared with primary untreated tumors in matched GBM patients. We designed a NEK2 kinase inhibitor, compound 3a (CMP3a), which efficiently attenuated GBM growth in a mouse model and exhibited a synergistic effect with radiotherapy. These data demonstrate a key role for NEK2 in maintaining GSCs in GBM by stabilizing the EZH2 protein and introduce the small-molecule inhibitor CMP3a as a potential therapeutic agent for GBM.
[Mh] Termos MeSH primário: Neoplasias Encefálicas/tratamento farmacológico
Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo
Glioblastoma/tratamento farmacológico
Quinases Relacionadas a NIMA/antagonistas & inibidores
[Mh] Termos MeSH secundário: Animais
Antineoplásicos/farmacologia
Neoplasias Encefálicas/radioterapia
Feminino
Inativação Gênica
Glioblastoma/radioterapia
Seres Humanos
Camundongos
Camundongos Nus
Quinases Relacionadas a NIMA/química
Transplante de Neoplasias
Células-Tronco Neoplásicas/metabolismo
Fosforilação
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); EC 2.1.1.43 (EZH2 protein, human); EC 2.1.1.43 (Enhancer of Zeste Homolog 2 Protein); EC 2.1.1.43 (Ezh2 protein, mouse); EC 2.7.11.1 (NEK2 protein, human); EC 2.7.11.1 (NIMA-Related Kinases); EC 2.7.11.1 (Nek2 protein, mouse)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171101
[Lr] Data última revisão:
171101
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170725
[St] Status:MEDLINE


  3 / 363 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28724347
[Au] Autor:Marina Perez A; Aquino B; Viviani V; Kobarg J
[Ad] Endereço:Instituto de Biologia, Departamento Bioquímica e Biologia Tecidual, Universidade Estadual de Campinas, Campinas, Programa de Pós-gradução em Biologia Molecular e Funcional São Paulo, Rua Monteiro Lobato 255, Campinas, SP, CEP 13083-862, Brazil.
[Ti] Título:Use of a special Brazilian red-light emitting railroad worm Luciferase in bioassays of NEK7 protein Kinase and Creatine Kinase.
[So] Source:BMC Biochem;18(1):12, 2017 Jul 19.
[Is] ISSN:1471-2091
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Luciferases, enzymes that catalyze bioluminescent reactions in different organisms, have been extensively used for bioanalytical purposes. The most well studied bioluminescent system is that of firefly and other beetles, which depends on a luciferase, a benzothiazolic luciferin and ATP, and it is being widely used as a bioanalytical reagent to quantify ATP. Protein kinases are proteins that modify other proteins by transferring phosphate groups from a nucleoside triphosphate, usually ATP. METHODS: Here, we used a red-light emitting luciferase from Phrixotrix hirtus railroad worm to determine the activity of kinases in a coupled assay, based on luminescence that is generated when luciferase is in the presence of its substrate, the luciferin, and ATP. RESULTS: In this work we used, after several optimization reactions, creatine kinase isoforms as well as NEK7 protein kinase in the absence or presence of ATP analogous inhibitors  to validate this new luminescence method. CONCLUSION: With this new approach we validated a luminescence method to quantify kinase activity, with different substrates and inhibition screening tests, using a novel red-light emitting luciferase as a reporter enzyme.
[Mh] Termos MeSH primário: Creatina Quinase/análise
Luciferases/análise
Medições Luminescentes/métodos
Quinases Relacionadas a NIMA/análise
Proteínas Quinases/análise
[Mh] Termos MeSH secundário: Trifosfato de Adenosina/química
Animais
Brasil
Luciferina de Vaga-Lumes/química
Luminescência
Medições Luminescentes/normas
[Pt] Tipo de publicação:JOURNAL ARTICLE; VALIDATION STUDIES
[Nm] Nome de substância:
5TBB02N29K (Firefly Luciferin); 8L70Q75FXE (Adenosine Triphosphate); EC 1.13.12.- (Luciferases); EC 2.7.- (Protein Kinases); EC 2.7.11.1 (NEK7 protein, human); EC 2.7.11.1 (NIMA-Related Kinases); EC 2.7.3.2 (Creatine Kinase)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170817
[Lr] Data última revisão:
170817
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170721
[St] Status:MEDLINE
[do] DOI:10.1186/s12858-017-0087-z


  4 / 363 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28720575
[Au] Autor:Sampson J; O'Regan L; Dyer MJS; Bayliss R; Fry AM
[Ad] Endereço:Department of Molecular and Cell Biology, University of Leicester, Leicester, United Kingdom.
[Ti] Título:Hsp72 and Nek6 Cooperate to Cluster Amplified Centrosomes in Cancer Cells.
[So] Source:Cancer Res;77(18):4785-4796, 2017 Sep 15.
[Is] ISSN:1538-7445
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Cancer cells frequently possess extra amplified centrosomes clustered into two poles whose pseudo-bipolar spindles exhibit reduced fidelity of chromosome segregation and promote genetic instability. Inhibition of centrosome clustering triggers multipolar spindle formation and mitotic catastrophe, offering an attractive therapeutic approach to selectively kill cells with amplified centrosomes. However, mechanisms of centrosome clustering remain poorly understood. Here, we identify a new pathway that acts through NIMA-related kinase 6 (Nek6) and Hsp72 to promote centrosome clustering. Nek6, as well as its upstream activators polo-like kinase 1 and Aurora-A, targeted Hsp72 to the poles of cells with amplified centrosomes. Unlike some centrosome declustering agents, blocking Hsp72 or Nek6 function did not induce formation of acentrosomal poles, meaning that multipolar spindles were observable only in cells with amplified centrosomes. Inhibition of Hsp72 in acute lymphoblastic leukemia cells resulted in increased multipolar spindle frequency that correlated with centrosome amplification, while loss of Hsp72 or Nek6 function in noncancer-derived cells disturbs neither spindle formation nor mitotic progression. Hence, the Nek6-Hsp72 module represents a novel actionable pathway for selective targeting of cancer cells with amplified centrosomes. .
[Mh] Termos MeSH primário: Neoplasias da Mama/patologia
Centrossomo/patologia
Proteínas de Choque Térmico HSP72/metabolismo
Neuroblastoma/patologia
[Mh] Termos MeSH secundário: Animais
Apoptose
Aurora Quinase A/genética
Aurora Quinase A/metabolismo
Neoplasias da Mama/genética
Neoplasias da Mama/metabolismo
Proteínas de Ciclo Celular/genética
Proteínas de Ciclo Celular/metabolismo
Proliferação Celular
Centrossomo/metabolismo
Feminino
Proteínas de Choque Térmico HSP72/genética
Seres Humanos
Camundongos
Mitose/fisiologia
Quinases Relacionadas a NIMA/genética
Quinases Relacionadas a NIMA/metabolismo
Neuroblastoma/genética
Neuroblastoma/metabolismo
Proteínas Serina-Treonina Quinases/genética
Proteínas Serina-Treonina Quinases/metabolismo
Proteínas Proto-Oncogênicas/genética
Proteínas Proto-Oncogênicas/metabolismo
Fuso Acromático/metabolismo
Fuso Acromático/patologia
Células Tumorais Cultivadas
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cell Cycle Proteins); 0 (HSP72 Heat-Shock Proteins); 0 (Proto-Oncogene Proteins); EC 2.7.11.1 (Aurora Kinase A); EC 2.7.11.1 (NEK6 protein, human); EC 2.7.11.1 (NIMA-Related Kinases); EC 2.7.11.1 (Protein-Serine-Threonine Kinases); EC 2.7.11.1 (polo-like kinase 1)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171030
[Lr] Data última revisão:
171030
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170720
[St] Status:MEDLINE
[do] DOI:10.1158/0008-5472.CAN-16-3233


  5 / 363 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28630147
[Au] Autor:Cullati SN; Kabeche L; Kettenbach AN; Gerber SA
[Ad] Endereço:Department of Biochemistry and Cell Biology, Geisel School of Medicine at Dartmouth, Lebanon, NH.
[Ti] Título:A bifurcated signaling cascade of NIMA-related kinases controls distinct kinesins in anaphase.
[So] Source:J Cell Biol;216(8):2339-2354, 2017 Aug 07.
[Is] ISSN:1540-8140
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:In mitosis, cells undergo a precisely orchestrated series of spatiotemporal changes in cytoskeletal structure to divide their genetic material. These changes are coordinated by a sophisticated network of protein-protein interactions and posttranslational modifications. In this study, we report a bifurcation in a signaling cascade of the NIMA-related kinases (Neks) Nek6, Nek7, and Nek9 that is required for the localization and function of two kinesins essential for cytokinesis, Mklp2 and Kif14. We demonstrate that a Nek9, Nek6, and Mklp2 signaling module controls the timely localization and bundling activity of Mklp2 at the anaphase central spindle. We further show that a separate Nek9, Nek7, and Kif14 signaling module is required for the recruitment of the Rho-interacting kinase citron to the anaphase midzone. Our findings uncover an anaphase-specific function for these effector kinesins that is controlled by specific Nek kinase signaling modules to properly coordinate cytokinesis.
[Mh] Termos MeSH primário: Anáfase
Citocinese
Cinesina/metabolismo
Quinases Relacionadas a NIMA/metabolismo
Fuso Acromático/enzimologia
[Mh] Termos MeSH secundário: Trifosfato de Adenosina/metabolismo
Cromatografia de Afinidade
Células HeLa
Seres Humanos
Hidrólise
Peptídeos e Proteínas de Sinalização Intracelular/genética
Peptídeos e Proteínas de Sinalização Intracelular/metabolismo
Cinesina/genética
Quinases Relacionadas a NIMA/genética
Proteínas Oncogênicas/genética
Proteínas Oncogênicas/metabolismo
Fosforilação
Proteínas Serina-Treonina Quinases/genética
Proteínas Serina-Treonina Quinases/metabolismo
Interferência de RNA
Transdução de Sinais
Espectrometria de Massas em Tandem
Fatores de Tempo
Transfecção
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Intracellular Signaling Peptides and Proteins); 0 (KIF20A protein, human); 0 (Oncogene Proteins); 8L70Q75FXE (Adenosine Triphosphate); EC 2.7.1.- (citron-kinase); EC 2.7.11.1 (NEK6 protein, human); EC 2.7.11.1 (NEK7 protein, human); EC 2.7.11.1 (NEK9 protein, human); EC 2.7.11.1 (NIMA-Related Kinases); EC 2.7.11.1 (Protein-Serine-Threonine Kinases); EC 3.6.1.- (KIF14 protein, human); EC 3.6.4.4 (Kinesin)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170925
[Lr] Data última revisão:
170925
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170621
[St] Status:MEDLINE
[do] DOI:10.1083/jcb.201512055


  6 / 363 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28479381
[Au] Autor:Zhou H; Chen Q; Tan W; Qiu Z; Li S; Song Y; Gao S
[Ad] Endereço:Department of Anesthesia, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China; Sun Yat-sen University School of Medicine, Guangzhou, China.
[Ti] Título:Integrated clinicopathological features and gene microarray analysis of pancreatic neuroendocrine tumors.
[So] Source:Gene;625:72-77, 2017 Aug 20.
[Is] ISSN:1879-0038
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Pancreatic neuroendocrine tumors are relatively rare pancreatic neoplasms over the world. Investigations about molecular biology of PNETs are insufficient for nowadays. We aimed to explore the expression of messenger RNA and regulatory processes underlying pancreatic neuroendocrine tumors from different views. The expression profile of GSE73338 were downloaded, including samples with pancreatic neuroendocrine tumors. First, the Limma package was utilized to distinguish the differentially expressed messenger RNA. Gene Ontology classification and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were performed to explore the functions and pathways of target genes. In addition, we constructed a protein-protein interaction network. NEK2, UBE2C, TOP2A and PPP1R1A were revealed with continuous genomic alterations in higher tumor stage. 91 up-regulated and 36 down-regulated genes were identified to be differentially expressed in malignant PNETs. Locomotory behavior was significantly enriched for biological processes of metastasis PNETs. GCGR and GNAS were identified as the hub of proteins in the protein-protein interaction sub-network of malignant PNETs. We showed the gene expression differences in PNETs according to different clinicopathological aspects. NEK2, UBE2C, TOP2A are positively associated with high tumor grade, and PPP1R1A negatively. GCGR and GNAS are regarded as the hub of the PPI sub-network. CXCR4 may affect the progression of PNETs via the CXCR4-CXCL12-CXCR7 chemokine receptor axis. However, more studies are required.
[Mh] Termos MeSH primário: Regulação Neoplásica da Expressão Gênica
Redes Reguladoras de Genes
Tumores Neuroendócrinos/genética
Neoplasias Pancreáticas/genética
Mapas de Interação de Proteínas
[Mh] Termos MeSH secundário: Antígenos de Neoplasias/genética
Quimiocinas/genética
Cromograninas/genética
DNA Topoisomerases Tipo II/genética
Proteínas de Ligação a DNA/genética
Subunidades alfa Gs de Proteínas de Ligação ao GTP/genética
Seres Humanos
Quinases Relacionadas a NIMA/genética
Metástase Neoplásica
Tumores Neuroendócrinos/patologia
Neoplasias Pancreáticas/patologia
Proteínas de Ligação a Poli-ADP-Ribose
Proteína Fosfatase 1/genética
Enzimas de Conjugação de Ubiquitina/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antigens, Neoplasm); 0 (Chemokines); 0 (Chromogranins); 0 (DNA-Binding Proteins); 0 (Poly-ADP-Ribose Binding Proteins); EC 2.3.2.23 (UBE2C protein, human); EC 2.3.2.23 (Ubiquitin-Conjugating Enzymes); EC 2.7.11.1 (NEK2 protein, human); EC 2.7.11.1 (NIMA-Related Kinases); EC 3.1.3.16 (Protein Phosphatase 1); EC 3.6.1.- (GNAS protein, human); EC 3.6.5.1 (GTP-Binding Protein alpha Subunits, Gs); EC 5.99.1.3 (DNA Topoisomerases, Type II); EC 5.99.1.3 (TOP2A protein, human)
[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:170509
[St] Status:MEDLINE


  7 / 363 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28475000
[Au] Autor:Wang Y; Shen H; Yin Q; Zhang T; Liu Z; Zhang W; Niu Y
[Ad] Endereço:1 Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy of Tianjin, Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Ministry of Education, Tianjin, China.
[Ti] Título:Effect of NIMA-related kinase 2B on the sensitivity of breast cancer to paclitaxel in vitro and vivo.
[So] Source:Tumour Biol;39(5):1010428317699754, 2017 May.
[Is] ISSN:1423-0380
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:NIMA-related kinase 2B has been known to be an important centrosome regulatory factor. The aim of this study was to investigate the effect of NIMA-related kinase 2B on the sensitivity of breast cancer to paclitaxel. We detected the expression of NIMA-related kinase 2B messenger RNA in MCF-10 cells, including MCF-10A, MCF-10AT, MCF-10DCIS.com , and MCF-10CA1a. The influence of NIMA-related kinase 2B in nude mouse was also detected. The association between NIMA-related kinase 2B and clinicopathological factors was explored in invasive ductal carcinoma tissues. NIMA-related kinase 2B was lowly expressed in the precancerous cells, MCF-10A and MCF-10AT, and it was highly expressed in carcinomatous cells, MCF-10DCIS.com and MCF-10CA1a. The upregulation of NIMA-related kinase 2B can introduce the growth of MCF-10AT cells, knockdown of NIMA-related kinase 2B could remarkably inhibit cell proliferation in MCF-10DCIS.com and MCF-10 CA1a cells. Comparing the volume of the xenografts in nude mouse, we found that the tumors treated by NIMA-related kinase 2B small interfering RNA associated with paclitaxel were the smallest among all the groups. Expression of NIMA-related kinase 2B messenger RNA was associated with higher histological grades, positive lymph node, and high Ki67 index (>20%). The partial response rates were 75.0% in NIMA-related kinase 2B negative (NIMA-related kinase 2B-) patients and 15.8% in NIMA-related kinase 2B++ patients. The progressive disease rates were 10.0% in NIMA-related kinase 2B- patients and 52.6% in NIMA-related kinase 2B++ patients ( p = 0.002). Our findings suggested that NIMA-related kinase 2B could play a role in the development and progression of breast cancer. Combination treatment using NIMA-related kinase 2B small interfering RNA and paclitaxel might be a novel potential therapy method for breast cancer.
[Mh] Termos MeSH primário: Neoplasias da Mama/tratamento farmacológico
Resistência a Medicamentos Antineoplásicos/genética
Quinases Relacionadas a NIMA/genética
Paclitaxel/administração & dosagem
[Mh] Termos MeSH secundário: Idoso
Animais
Apoptose/efeitos dos fármacos
Neoplasias da Mama/genética
Neoplasias da Mama/patologia
Linhagem Celular Tumoral
Proliferação Celular/efeitos dos fármacos
Feminino
Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos
Seres Humanos
Camundongos
Meia-Idade
Quinases Relacionadas a NIMA/biossíntese
Ensaios Antitumorais Modelo de Xenoenxerto
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
EC 2.7.11.1 (NIMA-Related Kinases); P88XT4IS4D (Paclitaxel)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170613
[Lr] Data última revisão:
170613
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170506
[St] Status:MEDLINE
[do] DOI:10.1177/1010428317699754


  8 / 363 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28216227
[Au] Autor:Tan R; Nakajima S; Wang Q; Sun H; Xue J; Wu J; Hellwig S; Zeng X; Yates NA; Smithgall TE; Lei M; Jiang Y; Levine AS; Su B; Lan L
[Ad] Endereço:Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan 410008, China; University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, 5117 Centre Avenue, Pittsburgh, PA 15213, USA; Department of Microbiology and Molecular Genetics, University of Pittsbur
[Ti] Título:Nek7 Protects Telomeres from Oxidative DNA Damage by Phosphorylation and Stabilization of TRF1.
[So] Source:Mol Cell;65(5):818-831.e5, 2017 Mar 02.
[Is] ISSN:1097-4164
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Telomeric repeat binding factor 1 (TRF1) is essential to the maintenance of telomere chromatin structure and integrity. However, how telomere integrity is maintained, especially in response to damage, remains poorly understood. Here, we identify Nek7, a member of the Never in Mitosis Gene A (NIMA) kinase family, as a regulator of telomere integrity. Nek7 is recruited to telomeres and stabilizes TRF1 at telomeres after damage in an ATM activation-dependent manner. Nek7 deficiency leads to telomere aberrations, long-lasting γH2AX and 53BP1 foci, and augmented cell death upon oxidative telomeric DNA damage. Mechanistically, Nek7 interacts with and phosphorylates TRF1 on Ser114, which prevents TRF1 from binding to Fbx4, an Skp1-Cul1-F box E3 ligase subunit, thereby alleviating proteasomal degradation of TRF1, leading to a stable association of TRF1 with Tin2 to form a shelterin complex. Our data reveal a mechanism of efficient protection of telomeres from damage through Nek7-dependent stabilization of TRF1.
[Mh] Termos MeSH primário: Dano ao DNA
Quinases Relacionadas a NIMA/metabolismo
Estresse Oxidativo
Proteínas de Ligação a Telômeros/metabolismo
Telômero/enzimologia
[Mh] Termos MeSH secundário: Proteínas Mutadas de Ataxia Telangiectasia/genética
Proteínas Mutadas de Ataxia Telangiectasia/metabolismo
Sítios de Ligação
Proteínas F-Box/genética
Proteínas F-Box/metabolismo
Células HEK293
Células HeLa
Histonas/metabolismo
Seres Humanos
Quinases Relacionadas a NIMA/genética
Fosforilação
Complexo de Endopeptidases do Proteassoma/metabolismo
Ligação Proteica
Estabilidade Proteica
Interferência de RNA
Telômero/genética
Telômero/efeitos da radiação
Proteínas de Ligação a Telômeros/genética
Fatores de Tempo
Transfecção
Proteína 1 de Ligação à Proteína Supressora de Tumor p53/genética
Proteína 1 de Ligação à Proteína Supressora de Tumor p53/metabolismo
Ubiquitinação
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (F-Box Proteins); 0 (FBXO4 protein, human); 0 (H2AFX protein, human); 0 (Histones); 0 (TERF1 protein, human); 0 (TINF2 protein, human); 0 (TP53BP1 protein, human); 0 (Telomere-Binding Proteins); 0 (Tumor Suppressor p53-Binding Protein 1); EC 2.7.11.1 (ATM protein, human); EC 2.7.11.1 (Ataxia Telangiectasia Mutated Proteins); EC 2.7.11.1 (NEK7 protein, human); EC 2.7.11.1 (NIMA-Related Kinases); EC 3.4.25.1 (Proteasome Endopeptidase Complex)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170906
[Lr] Data última revisão:
170906
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170221
[St] Status:MEDLINE


  9 / 363 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28101574
[Au] Autor:Li G; Zhong Y; Shen Q; Zhou Y; Deng X; Li C; Chen J; Zhou Y; He M
[Ad] Endereço:Medical Scientific Research Center, Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
[Ti] Título:NEK2 serves as a prognostic biomarker for hepatocellular carcinoma.
[So] Source:Int J Oncol;50(2):405-413, 2017 Feb.
[Is] ISSN:1791-2423
[Cp] País de publicação:Greece
[La] Idioma:eng
[Ab] Resumo:Never in mitosis gene A (NIMA)-related kinase 2 (NEK2) is a microtubule-associated protein that regulates spindle assembly in human cells and is overexpressed in various malignancies. However, the role of NEK2 in hepatocellular carcinoma (HCC) remains undetermined. We performed RNA-seq of the HCC cell line SMMC-7721 and the normal liver cell line HL-7702 using the Ion Proton System. NEK2 expression was detected using quantitative reverse transcription polymerase chain reaction in two cell lines and 5 matched HCC and adjacent non-tumorous liver tissues. The correlation between survival and NEK2 expression was analyzed in 359 patients with HCC using RNASeqV2 data available from The Cancer Genome Atlas (TCGA) website (https://tcga-data.nci.nih.gov/tcga/). The expression of NEK2, phospho-AKT and MMP-2 was evaluated by immunohistochemistry in 63 cases of HCC and matched adjacent non-tumorous liver tissues. Relationships between protein expression and clinicopathological parameters were assessed, and the correlations between NEK2 with phospho-AKT and MMP-2 expressions were evaluated. A total of 610 differentially expressed genes (DEGs) were revealed in the transcriptome comparison, 297 of which were upregulated and 313 were downregulated in HCC. NEK2, as the most obviously different DEG in cells and tissues from the RNA-seq data, was listed as an HCC candidate biomarker for further verification. NEK2 was overexpressed in HCC cells and tissues (P=0.002, P=0.013) and HCC patients with a high expression of NEK2 had a poor prognosis (P=0.0145). Clinical analysis indicated that the overexpression of NEK2 in HCC was significantly correlated with diolame complete (P<0.001), tumor nodule number (P=0.012) and recurrence (P=0.004). NEK2 expression was positively correlated with the expression of phospho-AKT (r=0.883, P<0.01) and MMP-2 (r=0.781, P<0.01). Overexpression of NEK2 was associated with clinicopathological characteristics and poor patient outcomes, suggesting that NEK2 serves as a prognostic biomarker for HCC. Alteration of NEK2 protein levels may contribute to invasion and metastasis of HCC, which may occur through activation of AKT signaling and promotion of MMP-2 expression.
[Mh] Termos MeSH primário: Biomarcadores Tumorais/análise
Carcinoma Hepatocelular/patologia
Neoplasias Hepáticas/patologia
Quinases Relacionadas a NIMA/biossíntese
[Mh] Termos MeSH secundário: Adulto
Idoso
Carcinoma Hepatocelular/mortalidade
Feminino
Seres Humanos
Imuno-Histoquímica
Estimativa de Kaplan-Meier
Neoplasias Hepáticas/mortalidade
Masculino
Meia-Idade
Quinases Relacionadas a NIMA/análise
Prognóstico
Reação em Cadeia da Polimerase Via Transcriptase Reversa
Transcriptoma
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers, Tumor); EC 2.7.11.1 (NEK2 protein, human); EC 2.7.11.1 (NIMA-Related Kinases)
[Em] Mês de entrada:1704
[Cu] Atualização por classe:170427
[Lr] Data última revisão:
170427
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170120
[St] Status:MEDLINE
[do] DOI:10.3892/ijo.2017.3837


  10 / 363 MEDLINE  
              first record previous record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28039836
[Au] Autor:Xi JB; Fang YF; Frett B; Zhu ML; Zhu T; Kong YN; Guan FJ; Zhao Y; Zhang XW; Li HY; Ma ML; Hu W
[Ad] Endereço:Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, 3663 North Zhongshan Road, Shanghai 200062, China.
[Ti] Título:Structure-based design and synthesis of imidazo[1,2-a]pyridine derivatives as novel and potent Nek2 inhibitors with in vitro and in vivo antitumor activities.
[So] Source:Eur J Med Chem;126:1083-1106, 2017 Jan 27.
[Is] ISSN:1768-3254
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:We present herein the discovery and development of novel and potent Nek2 inhibitors with distinctive in vitro and in vivo antitumor activity based on an imidazo[1,2-a]pyridine scaffold. Our studies identified a nonlinear SAR for activity against both Nek2 and cancer cells. Bioisostere and structure-based design techniques were employed to identify compounds 42c (MBM-17, IC = 3.0 nM) and 42g (MBM-55, IC = 1.0 nM), which displayed low nanomolar activity and excellent selectivity for Nek2. Both compounds effectively inhibited the proliferation of cancer cells by inducing cell cycle arrest and apoptosis. Importantly, the salts form of these two compounds (MBM-17S and MBM-55S) significantly suppressed tumor growth in vivo without apparent toxicity based on appearance and changes in body weight. In summary, MBM-17 and MBM-55 displayed the potential for substantial therapeutic application in cancer treatment.
[Mh] Termos MeSH primário: Desenho de Drogas
Quinases Relacionadas a NIMA/antagonistas & inibidores
Nitrazepam/química
Piridinas/síntese química
Piridinas/farmacologia
[Mh] Termos MeSH secundário: Animais
Antineoplásicos/síntese química
Antineoplásicos/química
Antineoplásicos/farmacocinética
Antineoplásicos/farmacologia
Apoptose/efeitos dos fármacos
Linhagem Celular Tumoral
Proliferação Celular/efeitos dos fármacos
Técnicas de Química Sintética
Relação Dose-Resposta a Droga
Ensaios de Seleção de Medicamentos Antitumorais
Feminino
Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos
Seres Humanos
Pontos de Checagem da Fase M do Ciclo Celular/efeitos dos fármacos
Masculino
Camundongos
Simulação de Acoplamento Molecular
Quinases Relacionadas a NIMA/química
Quinases Relacionadas a NIMA/metabolismo
Poliploidia
Conformação Proteica
Inibidores de Proteínas Quinases/síntese química
Inibidores de Proteínas Quinases/química
Inibidores de Proteínas Quinases/farmacocinética
Inibidores de Proteínas Quinases/farmacologia
Piridinas/química
Piridinas/farmacocinética
Ratos
Relação Estrutura-Atividade
Ensaios Antitumorais Modelo de Xenoenxerto
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Protein Kinase Inhibitors); 0 (Pyridines); 9CLV70W7HS (Nitrazepam); EC 2.7.11.1 (NEK2 protein, human); EC 2.7.11.1 (NIMA-Related Kinases)
[Em] Mês de entrada:1702
[Cu] Atualização por classe:170222
[Lr] Data última revisão:
170222
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170101
[St] Status:MEDLINE



página 1 de 37 ir para página                         
   


Refinar a pesquisa
  Base de dados : MEDLINE Formulário avançado   

    Pesquisar no campo  
1  
2
3
 
           



Search engine: iAH v2.6 powered by WWWISIS

BIREME/OPAS/OMS - Centro Latino-Americano e do Caribe de Informação em Ciências da Saúde