Base de dados : MEDLINE
Pesquisa : G02.111.730 [Categoria DeCS]
Referências encontradas : 8 [refinar]
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  1 / 8 MEDLINE  
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[PMID]:29348634
[Au] Autor:Wood RJ; Ormsby AR; Radwan M; Cox D; Sharma A; Vöpel T; Ebbinghaus S; Oliveberg M; Reid GE; Dickson A; Hatters DM
[Ad] Endereço:Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, VIC, 3010, Australia.
[Ti] Título:A biosensor-based framework to measure latent proteostasis capacity.
[So] Source:Nat Commun;9(1):287, 2018 01 18.
[Is] ISSN:2041-1723
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The pool of quality control proteins (QC) that maintains protein-folding homeostasis (proteostasis) is dynamic but can become depleted in human disease. A challenge has been in quantitatively defining the depth of the QC pool. With a new biosensor, flow cytometry-based methods and mathematical modeling we measure the QC capacity to act as holdases and suppress biosensor aggregation. The biosensor system comprises a series of barnase kernels with differing folding stability that engage primarily with HSP70 and HSP90 family proteins. Conditions of proteostasis stimulation and stress alter QC holdase activity and aggregation rates. The method reveals the HSP70 chaperone cycle to be rate limited by HSP70 holdase activity under normal conditions, but this is overcome by increasing levels of the BAG1 nucleotide exchange factor to HSPA1A or activation of the heat shock gene cluster by HSF1 overexpression. This scheme opens new paths for biosensors of disease and proteostasis systems.
[Mh] Termos MeSH primário: Técnicas Biossensoriais/métodos
Citometria de Fluxo/métodos
Modelos Teóricos
Proteostase
[Mh] Termos MeSH secundário: Algoritmos
Western Blotting
Células HEK293
Proteínas de Choque Térmico HSP72/metabolismo
Proteínas de Choque Térmico HSP90/metabolismo
Fatores de Transcrição de Choque Térmico/metabolismo
Seres Humanos
Proteoma/metabolismo
Proteômica/métodos
Espectrometria de Massas em Tandem/métodos
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (HSF1 protein, human); 0 (HSP72 Heat-Shock Proteins); 0 (HSP90 Heat-Shock Proteins); 0 (Heat Shock Transcription Factors); 0 (Proteome)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180306
[Lr] Data última revisão:
180306
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180120
[St] Status:MEDLINE
[do] DOI:10.1038/s41467-017-02562-5


  2 / 8 MEDLINE  
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[PMID]:29343728
[Au] Autor:Carroll B; Otten EG; Manni D; Stefanatos R; Menzies FM; Smith GR; Jurk D; Kenneth N; Wilkinson S; Passos JF; Attems J; Veal EA; Teyssou E; Seilhean D; Millecamps S; Eskelinen EL; Bronowska AK; Rubinsztein DC; Sanz A; Korolchuk VI
[Ad] Endereço:Institute for Cell and Molecular Biosciences (ICaMB), Newcastle University Institute for Ageing (NUIA), Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne, NE4 5PL, UK.
[Ti] Título:Oxidation of SQSTM1/p62 mediates the link between redox state and protein homeostasis.
[So] Source:Nat Commun;9(1):256, 2018 01 17.
[Is] ISSN:2041-1723
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Cellular homoeostatic pathways such as macroautophagy (hereinafter autophagy) are regulated by basic mechanisms that are conserved throughout the eukaryotic kingdom. However, it remains poorly understood how these mechanisms further evolved in higher organisms. Here we describe a modification in the autophagy pathway in vertebrates, which promotes its activity in response to oxidative stress. We have identified two oxidation-sensitive cysteine residues in a prototypic autophagy receptor SQSTM1/p62, which allow activation of pro-survival autophagy in stress conditions. The Drosophila p62 homologue, Ref(2)P, lacks these oxidation-sensitive cysteine residues and their introduction into the protein increases protein turnover and stress resistance of flies, whereas perturbation of p62 oxidation in humans may result in age-related pathology. We propose that the redox-sensitivity of p62 may have evolved in vertebrates as a mechanism that allows activation of autophagy in response to oxidative stress to maintain cellular homoeostasis and increase cell survival.
[Mh] Termos MeSH primário: Autofagia
Proteostase
Espécies Reativas de Oxigênio/metabolismo
Proteína Sequestossoma-1/metabolismo
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Animais
Sobrevivência Celular/efeitos dos fármacos
Células Cultivadas
Drosophila melanogaster/citologia
Drosophila melanogaster/genética
Drosophila melanogaster/metabolismo
Células HEK293
Células HeLa
Seres Humanos
Peróxido de Hidrogênio/farmacologia
Camundongos Knockout
Oxidantes/farmacologia
Oxirredução
Homologia de Sequência de Aminoácidos
Proteína Sequestossoma-1/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Oxidants); 0 (Reactive Oxygen Species); 0 (Sequestosome-1 Protein); BBX060AN9V (Hydrogen Peroxide)
[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:180119
[St] Status:MEDLINE
[do] DOI:10.1038/s41467-017-02746-z


  3 / 8 MEDLINE  
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[PMID]:29293508
[Au] Autor:Hadizadeh Esfahani A; Sverchkova A; Saez-Rodriguez J; Schuppert AA; Brehme M
[Ad] Endereço:Joint Research Center for Computational Biomedicine (JRC-COMBINE), RWTH Aachen University, Aachen, Germany.
[Ti] Título:A systematic atlas of chaperome deregulation topologies across the human cancer landscape.
[So] Source:PLoS Comput Biol;14(1):e1005890, 2018 01.
[Is] ISSN:1553-7358
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Proteome balance is safeguarded by the proteostasis network (PN), an intricately regulated network of conserved processes that evolved to maintain native function of the diverse ensemble of protein species, ensuring cellular and organismal health. Proteostasis imbalances and collapse are implicated in a spectrum of human diseases, from neurodegeneration to cancer. The characteristics of PN disease alterations however have not been assessed in a systematic way. Since the chaperome is among the central components of the PN, we focused on the chaperome in our study by utilizing a curated functional ontology of the human chaperome that we connect in a high-confidence physical protein-protein interaction network. Challenged by the lack of a systems-level understanding of proteostasis alterations in the heterogeneous spectrum of human cancers, we assessed gene expression across more than 10,000 patient biopsies covering 22 solid cancers. We derived a novel customized Meta-PCA dimension reduction approach yielding M-scores as quantitative indicators of disease expression changes to condense the complexity of cancer transcriptomics datasets into quantitative functional network topographies. We confirm upregulation of the HSP90 family and also highlight HSP60s, Prefoldins, HSP100s, ER- and mitochondria-specific chaperones as pan-cancer enriched. Our analysis also reveals a surprisingly consistent strong downregulation of small heat shock proteins (sHSPs) and we stratify two cancer groups based on the preferential upregulation of ATP-dependent chaperones. Strikingly, our analyses highlight similarities between stem cell and cancer proteostasis, and diametrically opposed chaperome deregulation between cancers and neurodegenerative diseases. We developed a web-based Proteostasis Profiler tool (Pro2) enabling intuitive analysis and visual exploration of proteostasis disease alterations using gene expression data. Our study showcases a comprehensive profiling of chaperome shifts in human cancers and sets the stage for a systematic global analysis of PN alterations across the human diseasome towards novel hypotheses for therapeutic network re-adjustment in proteostasis disorders.
[Mh] Termos MeSH primário: Chaperonas Moleculares/metabolismo
Neoplasias/metabolismo
Proteostase
[Mh] Termos MeSH secundário: Trifosfato de Adenosina/metabolismo
Biologia Computacional
Perfilação da Expressão Gênica
Seres Humanos
Redes e Vias Metabólicas
Modelos Biológicos
Chaperonas Moleculares/genética
Neoplasias/genética
Doenças Neurodegenerativas/genética
Doenças Neurodegenerativas/metabolismo
Mapas de Interação de Proteínas
Proteoma/genética
Proteoma/metabolismo
Deficiências na Proteostase/genética
Deficiências na Proteostase/metabolismo
Software
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Molecular Chaperones); 0 (Proteome); 8L70Q75FXE (Adenosine Triphosphate)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180128
[Lr] Data última revisão:
180128
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180103
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pcbi.1005890


  4 / 8 MEDLINE  
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[PMID]:28741509
[Au] Autor:Galmiche A; Sauzay C; Houessinon A; Chauffert B; Pluquet O
[Ad] Endereço:Service de Biochimie, Centre de Biologie Humaine (CBH), CHU Amiens Sud, France; EA4666, Université de Picardie Jules Verne (UPJV), Amiens, France. Electronic address: Galmiche.Antoine@chu-amiens.fr.
[Ti] Título:Probing Tumour Proteostasis and the UPR with Serum Markers.
[So] Source:Trends Cancer;2(5):219-221, 2016 May.
[Is] ISSN:2405-8025
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Tumour proteostasis and the unfolded protein response (UPR) are emerging drivers of tumour progression and important determinants of clinical efficacy of cancer therapy. Recent findings indicate that they also regulate the production of protein tumour markers. Here, we discuss how this new knowledge opens up new perspectives for cancer therapeutics.
[Mh] Termos MeSH primário: Biomarcadores/sangue
Neoplasias/sangue
Proteostase
Resposta a Proteínas não Dobradas
[Mh] Termos MeSH secundário: Seres Humanos
Neoplasias/tratamento farmacológico
Neoplasias/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180118
[Lr] Data última revisão:
180118
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170726
[St] Status:MEDLINE


  5 / 8 MEDLINE  
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[PMID]:29194454
[Au] Autor:Chen X; Dickman D
[Ad] Endereço:Department of Neurobiology, University of Southern California, Los Angeles, California, United States of America.
[Ti] Título:Development of a tissue-specific ribosome profiling approach in Drosophila enables genome-wide evaluation of translational adaptations.
[So] Source:PLoS Genet;13(12):e1007117, 2017 Dec.
[Is] ISSN:1553-7404
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Recent advances in next-generation sequencing approaches have revolutionized our understanding of transcriptional expression in diverse systems. However, measurements of transcription do not necessarily reflect gene translation, the process of ultimate importance in understanding cellular function. To circumvent this limitation, biochemical tagging of ribosome subunits to isolate ribosome-associated mRNA has been developed. However, this approach, called TRAP, lacks quantitative resolution compared to a superior technology, ribosome profiling. Here, we report the development of an optimized ribosome profiling approach in Drosophila. We first demonstrate successful ribosome profiling from a specific tissue, larval muscle, with enhanced resolution compared to conventional TRAP approaches. We next validate the ability of this technology to define genome-wide translational regulation. This technology is leveraged to test the relative contributions of transcriptional and translational mechanisms in the postsynaptic muscle that orchestrate the retrograde control of presynaptic function at the neuromuscular junction. Surprisingly, we find no evidence that significant changes in the transcription or translation of specific genes are necessary to enable retrograde homeostatic signaling, implying that post-translational mechanisms ultimately gate instructive retrograde communication. Finally, we show that a global increase in translation induces adaptive responses in both transcription and translation of protein chaperones and degradation factors to promote cellular proteostasis. Together, this development and validation of tissue-specific ribosome profiling enables sensitive and specific analysis of translation in Drosophila.
[Mh] Termos MeSH primário: Drosophila/genética
Sequenciamento de Nucleotídeos em Larga Escala/métodos
Biossíntese de Proteínas/genética
Subunidades Ribossômicas/genética
Análise de Sequência de RNA/métodos
[Mh] Termos MeSH secundário: Adaptação Fisiológica/genética
Animais
Drosophila/metabolismo
Feminino
Perfilação da Expressão Gênica
Regulação da Expressão Gênica
Chaperonas Moleculares/genética
Proteostase/genética
RNA Mensageiro/análise
Sensibilidade e Especificidade
[Pt] Tipo de publicação:JOURNAL ARTICLE; VALIDATION STUDIES
[Nm] Nome de substância:
0 (Molecular Chaperones); 0 (RNA, Messenger)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171229
[Lr] Data última revisão:
171229
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171202
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pgen.1007117


  6 / 8 MEDLINE  
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[PMID]:29220654
[Au] Autor:Guan BJ; van Hoef V; Jobava R; Elroy-Stein O; Valasek LS; Cargnello M; Gao XH; Krokowski D; Merrick WC; Kimball SR; Komar AA; Koromilas AE; Wynshaw-Boris A; Topisirovic I; Larsson O; Hatzoglou M
[Ad] Endereço:Department of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, OH 44106, USA.
[Ti] Título:A Unique ISR Program Determines Cellular Responses to Chronic Stress.
[So] Source:Mol Cell;68(5):885-900.e6, 2017 Dec 07.
[Is] ISSN:1097-4164
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The integrated stress response (ISR) is a homeostatic mechanism induced by endoplasmic reticulum (ER) stress. In acute/transient ER stress, decreased global protein synthesis and increased uORF mRNA translation are followed by normalization of protein synthesis. Here, we report a dramatically different response during chronic ER stress. This chronic ISR program is characterized by persistently elevated uORF mRNA translation and concurrent gene expression reprogramming, which permits simultaneous stress sensing and proteostasis. The program includes PERK-dependent switching to an eIF3-dependent translation initiation mechanism, resulting in partial, but not complete, translational recovery, which, together with transcriptional reprogramming, selectively bolsters expression of proteins with ER functions. Coordination of transcriptional and translational reprogramming prevents ER dysfunction and inhibits "foamy cell" development, thus establishing a molecular basis for understanding human diseases associated with ER dysfunction.
[Mh] Termos MeSH primário: Estresse do Retículo Endoplasmático
Fator de Iniciação 3 em Eucariotos/metabolismo
Fibroblastos/metabolismo
Biossíntese de Proteínas
RNA Mensageiro/biossíntese
Transcrição Genética
eIF-2 Quinase/metabolismo
[Mh] Termos MeSH secundário: Animais
Reprogramação Celular
Fator de Iniciação 3 em Eucariotos/genética
Fibroblastos/patologia
Células HEK293
Seres Humanos
Camundongos
Fases de Leitura Aberta
Fenótipo
Proteostase
Interferência de RNA
RNA Mensageiro/genética
Transdução de Sinais
Fatores de Tempo
Transfecção
eIF-2 Quinase/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Eukaryotic Initiation Factor-3); 0 (RNA, Messenger); EC 2.7.11.1 (PERK kinase); EC 2.7.11.1 (eIF-2 Kinase)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171226
[Lr] Data última revisão:
171226
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171209
[St] Status:MEDLINE


  7 / 8 MEDLINE  
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[PMID]:29167332
[Au] Autor:Walker CL; Pomatto LCD; Tripathi DN; Davies KJA
[Ad] Endereço:Center for Precision Environmental Health and Departments of Molecular & Cellular Biology and Medicine, Baylor College of Medicine, Houston, Texas; and Leonard Davis School of Gerontology of the Ethel Percy Andrus Gerontology Center and Division of Molecular & Computational Biology, Departme
[Ti] Título:Redox Regulation of Homeostasis and Proteostasis in Peroxisomes.
[So] Source:Physiol Rev;98(1):89-115, 2018 Jan 01.
[Is] ISSN:1522-1210
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Peroxisomes are highly dynamic intracellular organelles involved in a variety of metabolic functions essential for the metabolism of long-chain fatty acids, d-amino acids, and many polyamines. A byproduct of peroxisomal metabolism is the generation, and subsequent detoxification, of reactive oxygen and nitrogen species, particularly hydrogen peroxide (H O ). Because of its relatively low reactivity (as a mild oxidant), H O has a comparatively long intracellular half-life and a high diffusion rate, all of which makes H O an efficient signaling molecule. Peroxisomes also have intricate connections to mitochondria, and both organelles appear to play important roles in regulating redox signaling pathways. Peroxisomal proteins are also subject to oxidative modification and inactivation by the reactive oxygen and nitrogen species they generate, but the peroxisomal LonP2 protease can selectively remove such oxidatively damaged proteins, thus prolonging the useful lifespan of the organelle. Peroxisomal homeostasis must adapt to the metabolic state of the cell, by a combination of peroxisome proliferation, the removal of excess or badly damaged organelles by autophagy (pexophagy), as well as by processes of peroxisome inheritance and motility. More recently the tumor suppressors ataxia telangiectasia mutate (ATM) and tuberous sclerosis complex (TSC), which regulate mTORC1 signaling, have been found to regulate pexophagy in response to variable levels of certain reactive oxygen and nitrogen species. It is now clear that any significant loss of peroxisome homeostasis can have devastating physiological consequences. Peroxisome dysregulation has been implicated in several metabolic diseases, and increasing evidence highlights the important role of diminished peroxisomal functions in aging processes.
[Mh] Termos MeSH primário: Homeostase/fisiologia
Mitocôndrias/metabolismo
Peroxissomos/metabolismo
Proteostase/fisiologia
Espécies Reativas de Oxigênio/metabolismo
[Mh] Termos MeSH secundário: Animais
Homeostase/efeitos dos fármacos
Seres Humanos
Peróxido de Hidrogênio/farmacologia
Peroxissomos/efeitos dos fármacos
Proteostase/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Reactive Oxygen Species); BBX060AN9V (Hydrogen Peroxide)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171207
[Lr] Data última revisão:
171207
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171124
[St] Status:MEDLINE
[do] DOI:10.1152/physrev.00033.2016


  8 / 8 MEDLINE  
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[PMID]:29107114
[Au] Autor:Sklirou A; Papanagnou ED; Fokialakis N; Trougakos IP
[Ad] Endereço:Department of Cell Biology and Biophysics, Faculty of Biology, National and Kapodistrian University of Athens, Athens 15784, Greece.
[Ti] Título:Cancer chemoprevention via activation of proteostatic modules.
[So] Source:Cancer Lett;413:110-121, 2018 Jan 28.
[Is] ISSN:1872-7980
[Cp] País de publicação:Ireland
[La] Idioma:eng
[Ab] Resumo:Proteins carry out the majority of cellular functions and maintain cellular homeodynamics mostly by participating in multimeric assemblies that operate as protein machines. Proteome quality control is thus critical for cellular functionality, and it is carried out through the curating activity of the proteostasis network (PN). Key components of the PN are the protein synthesis and trafficking modules, the endoplasmic reticulum unfolded protein response, molecular chaperones, and the two main degradation machineries, namely the ubiquitin proteasome and autophagy lysosome pathways. Part of the PN are also several stress responsive pathways, including nuclear factor erythroid 2-related factor 2 (Nrf2), which mobilises genomic responses against oxidative and/or xenobiotic damage. Nevertheless, the gradual accumulation of stressors during ageing or earlier due to lifestyle results in an increasingly damaged and unstable proteome. This outcome may then increase genomic instability due to reduced DNA replication fidelity or repair, leading to various age-related diseases such as cancer. Considering that the activation of proteostatic modules exerts anti-ageing effects in model organisms, we present herein a synopsis of studies showing that proteostatic modules activation (e.g. by natural products) represents a promising tumour-chemopreventive approach.
[Mh] Termos MeSH primário: Anticarcinógenos/uso terapêutico
Transformação Celular Neoplásica/efeitos dos fármacos
Neoplasias/prevenção & controle
Proteoma/efeitos dos fármacos
Proteostase/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Proliferação Celular/efeitos dos fármacos
Transformação Celular Neoplásica/genética
Transformação Celular Neoplásica/metabolismo
Transformação Celular Neoplásica/patologia
Senescência Celular/efeitos dos fármacos
Regulação Neoplásica da Expressão Gênica
Seres Humanos
Neoplasias/genética
Neoplasias/metabolismo
Neoplasias/patologia
Estabilidade Proteica
Proteólise
Proteoma/genética
Proteoma/metabolismo
Proteostase/genética
Transdução de Sinais/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Anticarcinogenic Agents); 0 (Proteome)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171204
[Lr] Data última revisão:
171204
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171107
[St] Status:MEDLINE



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