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Pesquisa : D12.776.167 [Categoria DeCS]
Referências encontradas : 38830 [refinar]
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[PMID]:28903484
[Au] Autor:Yang Y; Gao X; Zhang M; Yan S; Sun C; Xiao F; Huang N; Yang X; Zhao K; Zhou H; Huang S; Xie B; Zhang N
[Ad] Endereço:Department of Neurosurgery, The 1st Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province, PR China; Guangdong Provincial Key Laboratory of Pituitary Tumor, Guangzhou, Guangdong Province, PR China; Department of Scientific Research Section, The 1st Affiliated Hospital of Sun Y
[Ti] Título:Novel Role of FBXW7 Circular RNA in Repressing Glioma Tumorigenesis.
[So] Source:J Natl Cancer Inst;110(3), 2018 Mar 01.
[Is] ISSN:1460-2105
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Background: Circular RNAs (circRNAs) are RNA transcripts that are widespread in the eukaryotic genome. Recent evidence indicates that circRNAs play important roles in tissue development, gene regulation, and carcinogenesis. However, whether circRNAs encode functional proteins remains elusive, although translation of several circRNAs was recently reported. Methods: CircRNA deep sequencing was performed by using 10 pathologically diagnosed glioblastoma samples and their paired adjacent normal brain tissues. Northern blotting, Sanger sequencing, antibody, and liquid chromatograph Tandem Mass Spectrometer were used to confirm the existence of circ-FBXW7 and its encoded protein in in two cell lines. Lentivirus-transfected stable U251 and U373 cells were used to assess the biological functions of the novel protein invitro and invivo (five mice per group). Clinical implications of circ-FBXW7 were assessed in 38 pathologically diagnosed glioblastoma samples and their paired periphery normal brain tissues by using quantitative polymerase chain reaction (two-sided log-rank test). Results: Circ-FBXW7 is abundantly expressed in the normal human brain (reads per kilobase per million mapped reads [RPKM] = 9.31). The spanning junction open reading frame in circ-FBXW7 driven by internal ribosome entry site encodes a novel 21-kDa protein, which we termed FBXW7-185aa. Upregulation of FBXW7-185aa in cancer cells inhibited proliferation and cell cycle acceleration, while knockdown of FBXW7-185aa promoted malignant phenotypes invitro and invivo. FBXW7-185aa reduced the half-life of c-Myc by antagonizing USP28-induced c-Myc stabilization. Moreover, circ-FBXW7 and FBXW7-185aa levels were reduced in glioblastoma clinical samples compared with their paired tumor-adjacent tissues (P < .001). Circ-FBXW7 expression positively associated with glioblastoma patient overall survival (P = .03). Conclusions: Endogenous circRNA encodes a functional protein in human cells, and circ-FBXW7 and FBXW7-185aa have potential prognostic implications in brain cancer.
[Mh] Termos MeSH primário: Neoplasias Encefálicas/genética
Proteínas de Ciclo Celular/genética
Transformação Celular Neoplásica/genética
Proteínas F-Box/genética
Glioblastoma/genética
RNA/análise
Ubiquitina-Proteína Ligases/genética
[Mh] Termos MeSH secundário: Animais
Encéfalo/metabolismo
Neoplasias Encefálicas/química
Ciclo Celular/genética
Proteínas de Ciclo Celular/análise
Linhagem Celular Tumoral
Proliferação Celular/genética
Proteínas F-Box/análise
Proteína 7 com Repetições F-Box-WD
Feminino
Glioblastoma/química
Meia-Vida
Seres Humanos
Camundongos
Camundongos Endogâmicos BALB C
Camundongos Nus
Transplante de Neoplasias
Fases de Leitura Aberta
Proteínas Proto-Oncogênicas c-myc/metabolismo
Análise de Sequência de RNA
Taxa de Sobrevida
Ubiquitina Tiolesterase/metabolismo
Ubiquitina-Proteína Ligases/análise
Regulação para Cima
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cell Cycle Proteins); 0 (F-Box Proteins); 0 (F-Box-WD Repeat-Containing Protein 7); 0 (FBXW7 protein, human); 0 (Proto-Oncogene Proteins c-myc); 0 (RNA, circular); 63231-63-0 (RNA); EC 2.3.2.27 (Ubiquitin-Protein Ligases); EC 3.1.2.15 (USP28 protein, human); EC 3.4.19.12 (Ubiquitin Thiolesterase)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170915
[St] Status:MEDLINE
[do] DOI:10.1093/jnci/djx166


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[PMID]:27773872
[Au] Autor:Willmore-Payne C; Damjanovich-Colmenares K; Pasi AV; Werner TL; Gulbahce HE; Downs-Kelly E; Geiersbach KB
[Ad] Endereço:From the ARUP Laboratories, Salt Lake City, UT.
[Ti] Título:Inconsistent Results With Different Secondary Reflex Assays for Resolving HER2 Status.
[So] Source:Am J Clin Pathol;146(5):618-626, 2016 Nov 01.
[Is] ISSN:1943-7722
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Objectives: Guidelines suggest that secondary reflex testing may be useful for resolving HER2 status in breast cancers with equivocal results by both immunohistochemistry (IHC) and in situ hybridization (ISH). We compared two reflex ISH assays and a polymerase chain reaction (PCR) assay for this application. Methods: Twenty-nine breast cancers with equivocal IHC and ISH results were retested two ways: (1) ISH using differentially labeled probes targeting ERBB2 ( HER2 , 17q12) and either RAI1 (17p11.2) or ORC4 (2q22.3-2q23.1) in two separate assays and (2) real-time quantitative PCR amplification of ERBB2 and a control locus ( EIF5B , 2q11.2). Results: Results of the HER2 / RAI1 and HER2 / ORC4 ISH assays were concordant for 21 (72%) cases, and results of all three secondary reflex assays were concordant for only 18 (62%) cases. Result discrepancies between the two ISH readers were observed for cases close to the cutoff threshold. Conclusions: Use of different control loci for ISH is associated with discordant results, and PCR is more likely to classify cases as nonamplified, possibly due to contamination with nontumor cells. While resolution of HER2 -equivocal results is desirable from a clinical perspective, different secondary reflex assays yield different results, and the correlation of these results with clinical outcomes is unknown.
[Mh] Termos MeSH primário: Biomarcadores Tumorais/metabolismo
Neoplasias da Mama/metabolismo
Receptor ErbB-2/metabolismo
[Mh] Termos MeSH secundário: Neoplasias da Mama/diagnóstico
Neoplasias da Mama/patologia
Proteínas de Ciclo Celular/genética
Proteínas de Ciclo Celular/metabolismo
Feminino
Seres Humanos
Imuno-Histoquímica
Hibridização In Situ
Complexo de Reconhecimento de Origem/genética
Complexo de Reconhecimento de Origem/metabolismo
Reação em Cadeia da Polimerase em Tempo Real
Receptor ErbB-2/genética
Reflexo
Fatores de Transcrição/genética
Fatores de Transcrição/metabolismo
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers, Tumor); 0 (Cell Cycle Proteins); 0 (ORC4 protein, human); 0 (Origin Recognition Complex); 0 (RAI1 protein, human); 0 (Transcription Factors); EC 2.7.10.1 (ERBB2 protein, human); EC 2.7.10.1 (Receptor, ErbB-2)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:161025
[St] Status:MEDLINE
[do] DOI:10.1093/ajcp/aqw177


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[PMID]:29295989
[Au] Autor:Gibori H; Eliyahu S; Krivitsky A; Ben-Shushan D; Epshtein Y; Tiram G; Blau R; Ofek P; Lee JS; Ruppin E; Landsman L; Barshack I; Golan T; Merquiol E; Blum G; Satchi-Fainaro R
[Ad] Endereço:Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, 69978, Israel.
[Ti] Título:Amphiphilic nanocarrier-induced modulation of PLK1 and miR-34a leads to improved therapeutic response in pancreatic cancer.
[So] Source:Nat Commun;9(1):16, 2018 01 02.
[Is] ISSN:2041-1723
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The heterogeneity of pancreatic ductal adenocarcinoma (PDAC) suggests that successful treatment might rely on simultaneous targeting of multiple genes, which can be achieved by RNA interference-based therapeutic strategies. Here we show a potent combination of microRNA and siRNA delivered by an efficient nanocarrier to PDAC tumors. Using proteomic-microRNA profiles and survival data of PDAC patients from TCGA, we found a novel signature for prolonged survival. Accordingly, we used a microRNA-mimic to increase miR-34a together with siRNA to silence PLK1 oncogene. For in vivo dual-targeting of this combination, we developed a biodegradable amphiphilic polyglutamate amine polymeric nanocarrier (APA). APA-miRNA-siRNA polyplexes systemically administered to orthotopically inoculated PDAC-bearing mice showed no toxicity and accumulated at the tumor, resulting in an enhanced antitumor effect due to inhibition of MYC oncogene, a common target of both miR-34a and PLK1. Taken together, our findings warrant this unique combined polyplex's potential as a novel nanotherapeutic for PDAC.
[Mh] Termos MeSH primário: Carcinoma Ductal Pancreático/genética
Proteínas de Ciclo Celular/genética
Regulação Neoplásica da Expressão Gênica
MicroRNAs/genética
Neoplasias Pancreáticas/genética
Proteínas Serina-Treonina Quinases/genética
Proteínas Proto-Oncogênicas/genética
RNA Interferente Pequeno/genética
[Mh] Termos MeSH secundário: Adulto
Idoso
Animais
Carcinoma Ductal Pancreático/metabolismo
Carcinoma Ductal Pancreático/terapia
Proteínas de Ciclo Celular/metabolismo
Linhagem Celular Tumoral
Portadores de Fármacos/química
Feminino
Seres Humanos
Interações Hidrofóbicas e Hidrofílicas
Estimativa de Kaplan-Meier
Masculino
Camundongos Endogâmicos C57BL
Camundongos SCID
Meia-Idade
Nanoestruturas/química
Neoplasias Pancreáticas/metabolismo
Neoplasias Pancreáticas/terapia
Proteínas Serina-Treonina Quinases/metabolismo
Proteínas Proto-Oncogênicas/metabolismo
Proteínas Proto-Oncogênicas c-myc/genética
Proteínas Proto-Oncogênicas c-myc/metabolismo
Interferência de RNA
RNA Interferente Pequeno/química
Terapêutica com RNAi/métodos
Ensaios Antitumorais Modelo de Xenoenxerto/métodos
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Cell Cycle Proteins); 0 (Drug Carriers); 0 (MIRN34 microRNA, human); 0 (MicroRNAs); 0 (Proto-Oncogene Proteins); 0 (Proto-Oncogene Proteins c-myc); 0 (RNA, Small Interfering); EC 2.7.11.1 (Protein-Serine-Threonine Kinases); EC 2.7.11.1 (polo-like kinase 1)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180305
[Lr] Data última revisão:
180305
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180104
[St] Status:MEDLINE
[do] DOI:10.1038/s41467-017-02283-9


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[PMID]:28467304
[Au] Autor:Hansen AS; Pustova I; Cattoglio C; Tjian R; Darzacq X
[Ad] Endereço:Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States.
[Ti] Título:CTCF and cohesin regulate chromatin loop stability with distinct dynamics.
[So] Source:Elife;6, 2017 05 03.
[Is] ISSN:2050-084X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Folding of mammalian genomes into spatial domains is critical for gene regulation. The insulator protein CTCF and cohesin control domain location by folding domains into loop structures, which are widely thought to be stable. Combining genomic and biochemical approaches we show that CTCF and cohesin co-occupy the same sites and physically interact as a biochemically stable complex. However, using single-molecule imaging we find that CTCF binds chromatin much more dynamically than cohesin (~1-2 min vs. ~22 min residence time). Moreover, after unbinding, CTCF quickly rebinds another cognate site unlike cohesin for which the search process is long (~1 min vs. ~33 min). Thus, CTCF and cohesin form a rapidly exchanging 'dynamic complex' rather than a typical stable complex. Since CTCF and cohesin are required for loop domain formation, our results suggest that chromatin loops are dynamic and frequently break and reform throughout the cell cycle.
[Mh] Termos MeSH primário: Fator de Ligação a CCCTC/metabolismo
Proteínas de Ciclo Celular/metabolismo
Cromatina/metabolismo
Proteínas Cromossômicas não Histona/metabolismo
[Mh] Termos MeSH secundário: Animais
Células Cultivadas
Cinética
Camundongos
Ligação Proteica
Mapeamento de Interação de Proteínas
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (CCCTC-Binding Factor); 0 (Cell Cycle Proteins); 0 (Chromatin); 0 (Chromosomal Proteins, Non-Histone); 0 (cohesins)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180305
[Lr] Data última revisão:
180305
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170504
[St] Status:MEDLINE


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[PMID]:28463114
[Au] Autor:Moura M; Osswald M; Leça N; Barbosa J; Pereira AJ; Maiato H; Sunkel CE; Conde C
[Ad] Endereço:i3S, Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal.
[Ti] Título:Protein Phosphatase 1 inactivates Mps1 to ensure efficient Spindle Assembly Checkpoint silencing.
[So] Source:Elife;6, 2017 05 02.
[Is] ISSN:2050-084X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Faithfull genome partitioning during cell division relies on the Spindle Assembly Checkpoint (SAC), a conserved signaling pathway that delays anaphase onset until all chromosomes are attached to spindle microtubules. Mps1 kinase is an upstream SAC regulator that promotes the assembly of an anaphase inhibitor through a sequential multi-target phosphorylation cascade. Thus, the SAC is highly responsive to Mps1, whose activity peaks in early mitosis as a result of its T-loop autophosphorylation. However, the mechanism controlling Mps1 inactivation once kinetochores attach to microtubules and the SAC is satisfied remains unknown. Here we show and in that Protein Phosphatase 1 (PP1) inactivates Mps1 by dephosphorylating its T-loop. PP1-mediated dephosphorylation of Mps1 occurs at kinetochores and in the cytosol, and inactivation of both pools of Mps1 during metaphase is essential to ensure prompt and efficient SAC silencing. Overall, our findings uncover a mechanism of SAC inactivation required for timely mitotic exit.
[Mh] Termos MeSH primário: Proteínas de Ciclo Celular/metabolismo
Divisão Celular
Segregação de Cromossomos
Proteínas de Drosophila/metabolismo
Drosophila/fisiologia
Pontos de Checagem da Fase M do Ciclo Celular
Proteína Fosfatase 1/metabolismo
Proteínas Serina-Treonina Quinases/metabolismo
[Mh] Termos MeSH secundário: Animais
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Cell Cycle Proteins); 0 (Drosophila Proteins); EC 2.7.11.1 (Protein-Serine-Threonine Kinases); EC 2.7.11.1 (ald protein, Drosophila); EC 3.1.3.16 (Protein Phosphatase 1)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180305
[Lr] Data última revisão:
180305
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170503
[St] Status:MEDLINE


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[PMID]:28464854
[Au] Autor:Chi L; Zou Y; Qin L; Ma W; Hao Y; Tang Y; Luo R; Wu Z
[Ad] Endereço:Cancer Center, TCM-Integrated Hospital, Southern Medical University, Guangzhou, 510315, China.
[Ti] Título:TIMELESS contributes to the progression of breast cancer through activation of MYC.
[So] Source:Breast Cancer Res;19(1):53, 2017 May 02.
[Is] ISSN:1465-542X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Breast cancer is the most common malignancy and the leading cause of cancer death among women. TIMELESS (TIM), a circadian rhythm regulator, has been recently implicated in the progression of human cancer. However, the role of TIM in the progression of breast cancer has not been well-characterized. METHODS: Immunohistochemistry (IHC) staining was used to examine TIM levels in breast cancer specimens. Mammosphere formation analysis and side population analysis were used to examine the effect of TIM on the self-renewal of breast cancer stem cells. A wound healing assay and a Transwell assay were used to determine the role of TIM in breast cancer cell migration and invasion. A soft agar growth assay in vitro and tumorigenicity in vivo were used to determine the role of TIM in tumorigenicity. RESULTS: TIM levels in both breast cancer cell lines and tissues were significantly upregulated. Patients with high TIM had poorer prognosis than patients with low TIM. Overexpression of TIM dramatically enhanced, while knockdown of TIM suppressed the self-renewal of cancer stem cells (CSCs), cell invasion and migration abilities of breast cancer cells in vitro. Moreover, overexpression of TIM significantly augmented, while knockdown of TIM reduced the tumorigenicity of breast cancer cells in vivo. Mechanism studies revealed that TIM upregulated the expression and the trans-activity of the well-known oncogene MYC. Inhibition of MYC significantly blocked the effects of TIM on CSC population, cell invasion and anchor-independent cell growth. CONCLUSION: TIM plays an important role in promoting breast cancer progression and may represent a novel therapeutic target for breast cancer.
[Mh] Termos MeSH primário: Neoplasias da Mama/genética
Proteínas de Ciclo Celular/genética
Proliferação Celular/genética
Peptídeos e Proteínas de Sinalização Intracelular/genética
Proteínas Proto-Oncogênicas c-myc/genética
[Mh] Termos MeSH secundário: Neoplasias da Mama/patologia
Progressão da Doença
Feminino
Regulação Neoplásica da Expressão Gênica
Seres Humanos
Células MCF-7
Invasividade Neoplásica/genética
Células-Tronco Neoplásicas/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cell Cycle Proteins); 0 (Intracellular Signaling Peptides and Proteins); 0 (MYC protein, human); 0 (Proto-Oncogene Proteins c-myc); 0 (TIMELESS protein, human)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180301
[Lr] Data última revisão:
180301
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170504
[St] Status:MEDLINE
[do] DOI:10.1186/s13058-017-0838-1


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[PMID]:29281624
[Au] Autor:Lafuente-Barquero J; Luke-Glaser S; Graf M; Silva S; Gómez-González B; Lockhart A; Lisby M; Aguilera A; Luke B
[Ad] Endereço:Andalusian Center for Molecular Biology and Regenerative Medicine-CABIMER, Universidad de Sevilla-CSIC-Universidad Pablo de Olavide, Avda. Americo Vespucio 24, Seville, Spain.
[Ti] Título:The Smc5/6 complex regulates the yeast Mph1 helicase at RNA-DNA hybrid-mediated DNA damage.
[So] Source:PLoS Genet;13(12):e1007136, 2017 12.
[Is] ISSN:1553-7404
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:RNA-DNA hybrids are naturally occurring obstacles that must be overcome by the DNA replication machinery. In the absence of RNase H enzymes, RNA-DNA hybrids accumulate, resulting in replication stress, DNA damage and compromised genomic integrity. We demonstrate that Mph1, the yeast homolog of Fanconi anemia protein M (FANCM), is required for cell viability in the absence of RNase H enzymes. The integrity of the Mph1 helicase domain is crucial to prevent the accumulation of RNA-DNA hybrids and RNA-DNA hybrid-dependent DNA damage, as determined by Rad52 foci. Mph1 forms foci when RNA-DNA hybrids accumulate, e.g. in RNase H or THO-complex mutants and at short telomeres. Mph1, however is a double-edged sword, whose action at hybrids must be regulated by the Smc5/6 complex. This is underlined by the observation that simultaneous inactivation of RNase H2 and Smc5/6 results in Mph1-dependent synthetic lethality, which is likely due to an accumulation of toxic recombination intermediates. The data presented here support a model, where Mph1's helicase activity plays a crucial role in responding to persistent RNA-DNA hybrids.
[Mh] Termos MeSH primário: Proteínas de Ciclo Celular/genética
RNA Helicases DEAD-box/genética
RNA Helicases DEAD-box/metabolismo
Dano ao DNA
RNA Fúngico/genética
Proteínas de Saccharomyces cerevisiae/genética
Proteínas de Saccharomyces cerevisiae/metabolismo
[Mh] Termos MeSH secundário: Proteínas de Ciclo Celular/metabolismo
DNA/metabolismo
Reparo do DNA
Replicação do DNA/genética
Replicação do DNA/fisiologia
RNA Helicases/metabolismo
RNA Fúngico/metabolismo
Ribonuclease H/genética
Saccharomyces cerevisiae/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Cell Cycle Proteins); 0 (RNA, Fungal); 0 (SMC5 protein, S cerevisiae); 0 (SMC6 protein, S cerevisiae); 0 (Saccharomyces cerevisiae Proteins); 9007-49-2 (DNA); EC 3.1.26.4 (Ribonuclease H); EC 3.6.1.- (MPH1 protein, S cerevisiae); EC 3.6.4.13 (DEAD-box RNA Helicases); EC 3.6.4.13 (RNA Helicases)
[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:171228
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pgen.1007136


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[PMID]:29261648
[Au] Autor:Zuin J; Casa V; Pozojevic J; Kolovos P; van den Hout MCGN; van Ijcken WFJ; Parenti I; Braunholz D; Baron Y; Watrin E; Kaiser FJ; Wendt KS
[Ad] Endereço:Department of Cell Biology, Erasmus MC, Rotterdam, The Netherlands.
[Ti] Título:Regulation of the cohesin-loading factor NIPBL: Role of the lncRNA NIPBL-AS1 and identification of a distal enhancer element.
[So] Source:PLoS Genet;13(12):e1007137, 2017 12.
[Is] ISSN:1553-7404
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Cohesin is crucial for genome stability, cell division, transcription and chromatin organization. Its functions critically depend on NIPBL, the cohesin-loader protein that is found to be mutated in >60% of the cases of Cornelia de Lange syndrome (CdLS). Other mutations are described in the cohesin subunits SMC1A, RAD21, SMC3 and the HDAC8 protein. In 25-30% of CdLS cases no mutation in the known CdLS genes is detected. Until now, functional elements in the noncoding genome were not characterized in the molecular etiology of CdLS and therefore are excluded from mutation screening, although the impact of such mutations has now been recognized for a wide range of diseases. We have identified different elements of the noncoding genome involved in regulation of the NIPBL gene. NIPBL-AS1 is a long non-coding RNA transcribed upstream and antisense to NIPBL. By knockdown and transcription blocking experiments, we could show that not the NIPBL-AS1 gene product, but its actual transcription is important to regulate NIPBL expression levels. This reveals a possibility to boost the transcriptional activity of the NIPBL gene by interfering with the NIPBL-AS1 lncRNA. Further, we have identified a novel distal enhancer regulating both NIPBL and NIPBL-AS1. Deletion of the enhancer using CRISPR genome editing in HEK293T cells reduces expression of NIPBL, NIPBL-AS1 as well as genes found to be dysregulated in CdLS.
[Mh] Termos MeSH primário: Elementos Facilitadores Genéticos
Oligonucleotídeos Antissenso/genética
Oligonucleotídeos Antissenso/metabolismo
Proteínas/genética
Proteínas/metabolismo
[Mh] Termos MeSH secundário: Proteínas de Ciclo Celular/genética
Proteínas de Ciclo Celular/metabolismo
Proteínas Cromossômicas não Histona/genética
Proteínas Cromossômicas não Histona/metabolismo
Segregação de Cromossomos
Síndrome de Lange/genética
Regulação da Expressão Gênica
Genoma Humano
Células HEK293
Seres Humanos
Mutação
Fenótipo
Regiões Promotoras Genéticas
RNA Longo não Codificante/genética
RNA Longo não Codificante/metabolismo
Análise de Sequência de DNA
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Cell Cycle Proteins); 0 (Chromosomal Proteins, Non-Histone); 0 (NIPBL protein, human); 0 (Oligonucleotides, Antisense); 0 (Proteins); 0 (RNA, Long Noncoding); 0 (cohesins)
[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:171221
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pgen.1007137


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[PMID]:28453390
[Au] Autor:Chavda AP; Ang K; Ivanov D
[Ad] Endereço:a Bioinformatics Institute, A*STAR , Singapore.
[Ti] Título:The torments of the cohesin ring.
[So] Source:Nucleus;8(3):261-267, 2017 May 04.
[Is] ISSN:1949-1042
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Cohesin is a ring-shaped protein complex which comprises the Smc1, Smc3 and Scc1 subunits. It topologically embraces chromosomal DNA to connect sister chromatids and stabilize chromatin loops. It is required for proper chromosomal segregation, DNA repair and transcriptional regulation. We have recently reported that cohesin rings can adopt a "collapsed" rod-like conformation which is driven by the interaction between the Smc1 and Smc3 coiled coil arms and is regulated by post-translational modifications. The "collapsed" conformation plays a role in cohesin ring assembly and its loading on the DNA. Here we speculate about the mechanism of cohesin's conformational transitions in relation to its loading on the DNA and draw parallels with other Smc-like complexes.
[Mh] Termos MeSH primário: Proteínas de Ciclo Celular/metabolismo
Proteínas Cromossômicas não Histona/metabolismo
[Mh] Termos MeSH secundário: Trifosfato de Adenosina/metabolismo
Animais
Proteínas de Ciclo Celular/química
Proteínas Cromossômicas não Histona/química
DNA/genética
DNA/metabolismo
Seres Humanos
Hidrólise
Conformação Proteica
Processamento de Proteína Pós-Traducional
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Cell Cycle Proteins); 0 (Chromosomal Proteins, Non-Histone); 0 (cohesins); 8L70Q75FXE (Adenosine Triphosphate); 9007-49-2 (DNA)
[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:170429
[St] Status:MEDLINE
[do] DOI:10.1080/19491034.2017.1295200


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[PMID]:29288948
[Au] Autor:Pan Z; Chen Y; Liu J; Jiang Q; Yang S; Guo L; He G
[Ad] Endereço:Key Laboratory of Drug-Targeting of Education Ministry and Department of Medicinal Chemistry, West China School of Pharmacy, Sichuan University, Chengdu 610041, China; State Key Laboratory of Biotherapy and Department of Breast Surgery, West China Hospital, Sichuan University and Collaborative Innov
[Ti] Título:Design, synthesis, and biological evaluation of polo-like kinase 1/eukaryotic elongation factor 2 kinase (PLK1/EEF2K) dual inhibitors for regulating breast cancer cells apoptosis and autophagy.
[So] Source:Eur J Med Chem;144:517-528, 2018 Jan 20.
[Is] ISSN:1768-3254
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:Both PLK1 and EEF2K are serine/threonine kinases that play important roles in the proliferation and programmed cell death of various types of cancer. They are highly expressed in breast cancer tissues. Based on the multiple-complexes generated pharmacophore models of PLK1 and homology models of EEF2K, the integrated virtual screening is performed to discover novel PLK1/EEF2K dual inhibitors. The top ten hit compounds are selected and tested in vitro, and five of them display PLK1 and EEF2K inhibition in vitro. Based on the docking modes of the most potent hit compound, a series of derivatives are synthesized, characterized and biological assayed on the PLK1, EEF2K as well as breast cancer cell proliferation models. Compound 18i with satisfied inhibitory potency are shifted to molecular mechanism studies contained molecular dynamics simulations, cell cycles, apoptosis and autophagy assays. Our results suggested that these novel PLK1/EEF2K dual inhibitors can be used as lead compounds for further development breast cancer chemotherapy.
[Mh] Termos MeSH primário: Antineoplásicos/farmacologia
Apoptose/efeitos dos fármacos
Neoplasias da Mama/tratamento farmacológico
Proteínas de Ciclo Celular/antagonistas & inibidores
Desenho de Drogas
Quinase do Fator 2 de Elongação/antagonistas & inibidores
Inibidores de Proteínas Quinases/farmacologia
Proteínas Serina-Treonina Quinases/antagonistas & inibidores
Proteínas Proto-Oncogênicas/antagonistas & inibidores
[Mh] Termos MeSH secundário: Antineoplásicos/síntese química
Antineoplásicos/química
Neoplasias da Mama/metabolismo
Neoplasias da Mama/patologia
Proteínas de Ciclo Celular/metabolismo
Linhagem Celular Tumoral
Proliferação Celular/efeitos dos fármacos
Relação Dose-Resposta a Droga
Ensaios de Seleção de Medicamentos Antitumorais
Quinase do Fator 2 de Elongação/metabolismo
Feminino
Seres Humanos
Simulação de Acoplamento Molecular
Estrutura Molecular
Inibidores de Proteínas Quinases/síntese química
Inibidores de Proteínas Quinases/química
Proteínas Serina-Treonina Quinases/metabolismo
Proteínas Proto-Oncogênicas/metabolismo
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Cell Cycle Proteins); 0 (Protein Kinase Inhibitors); 0 (Proto-Oncogene Proteins); EC 2.7.1.17 (EEF2K protein, human); EC 2.7.11.1 (Protein-Serine-Threonine Kinases); EC 2.7.11.1 (polo-like kinase 1); EC 2.7.11.20 (Elongation Factor 2 Kinase)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180223
[Lr] Data última revisão:
180223
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171231
[St] Status:MEDLINE



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