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[PMID]:28463112
[Au] Autor:Edens BM; Yan J; Miller N; Deng HX; Siddique T; Ma YC
[Ad] Endereço:Department of Pediatrics, Northwestern University Feinberg School of Medicine, Ann & Robert H Lurie Children's Hospital of Chicago, Chicago, United States.
[Ti] Título:A novel ALS-associated variant in regulates motor axon morphogenesis.
[So] Source:Elife;6, 2017 05 02.
[Is] ISSN:2050-084X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The etiological underpinnings of amyotrophic lateral sclerosis (ALS) are complex and incompletely understood, although contributions to pathogenesis by regulators of proteolytic pathways have become increasingly apparent. Here, we present a novel variant in that is associated with ALS and show that its expression compromises motor axon morphogenesis in mouse motor neurons and in zebrafish. We further demonstrate that the ALS-associated variant impairs proteasomal function, and identify the Wnt signaling pathway effector beta-catenin as a substrate. Inhibition of beta-catenin function rescues the variant-induced motor axon phenotypes. These findings provide a strong link between the regulation of axonal morphogenesis and a new ALS-associated gene variant mediated by protein degradation pathways.
[Mh] Termos MeSH primário: Esclerose Amiotrófica Lateral/genética
Esclerose Amiotrófica Lateral/patologia
Proteínas de Transporte/genética
Morfogênese
Neurônios Motores/citologia
Proteínas Nucleares/genética
[Mh] Termos MeSH secundário: Animais
Modelos Animais de Doenças
Camundongos
Complexo de Endopeptidases do Proteassoma/metabolismo
Proteólise
Peixe-Zebra
beta Catenina/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (Carrier Proteins); 0 (Nuclear Proteins); 0 (UBQLN4 protein, human); 0 (beta Catenin); EC 3.4.25.1 (Proteasome Endopeptidase Complex)
[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]:28460458
[Au] Autor:Fang Y; Wang J; Wang G; Zhou C; Wang P; Zhao S; Zhao S; Huang S; Su W; Jiang P; Chang A; Xiang R; Sun P
[Ad] Endereço:Department of Immunology, School of Medicine, Nankai University, Tianjin, China.
[Ti] Título:Inactivation of p38 MAPK contributes to stem cell-like properties of non-small cell lung cancer.
[So] Source:Oncotarget;8(16):26702-26717, 2017 Apr 18.
[Is] ISSN:1949-2553
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Cancer stem cells (CSCs) are recognized as the major source for cancer initiation and recurrence. Yet, the mechanism by which the cancer stem cell properties are acquired and maintained in a cancer cell population is not well understood. In the current study, we observed that the level of active p38 MAPK is downregulated, while the level of the stemness marker SOX2 is upregulated in lung cancer tissues as compared to normal tissues. We further demonstrated that inactivation of p38 is a potential mechanism contributing to acquisition and maintenance of cancer stem cell properties in non-small cell lung cancer (NSCLC) cells. p38, in particular the p38γ and p38δ isoforms, suppresses the cancer stem cell properties and tumor initiating ability of NSCLC cells by promoting the ubiquitylation and degradation of stemness proteins such as SOX2, Oct4, Nanog, Klf4 and c-Myc, through MK2-mediated phosphorylation of Hsp27 that is an essential component of the proteasomal degradation machinery. In contrast, inactivation of p38 in lung cancer cells leads to upregulation of the stemness proteins, thus promoting the cancer stem cell properties of these cells. These findings have demonstrated a novel mechanism by which cancer stem cell properties are acquired and maintained in a cancer cell population, and have revealed a new function of the p38 pathway in suppressing cancer development. These studies have also identified a new pathway that can potentially serve as a target for cancer therapies aimed at eliminating CSCs.
[Mh] Termos MeSH primário: Carcinoma Pulmonar de Células não Pequenas/metabolismo
Neoplasias Pulmonares/metabolismo
Células-Tronco Neoplásicas/metabolismo
Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
[Mh] Termos MeSH secundário: Animais
Biomarcadores
Carcinoma Pulmonar de Células não Pequenas/genética
Linhagem Celular Tumoral
Transformação Celular Neoplásica/genética
Transformação Celular Neoplásica/metabolismo
Modelos Animais de Doenças
Ativação Enzimática
Regulação Neoplásica da Expressão Gênica
Xenoenxertos
Seres Humanos
Neoplasias Pulmonares/genética
Masculino
Camundongos
Fosforilação
Complexo de Endopeptidases do Proteassoma/metabolismo
Estabilidade Proteica
Proteólise
Fatores de Transcrição SOXB1/genética
Fatores de Transcrição SOXB1/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers); 0 (SOX2 protein, human); 0 (SOXB1 Transcription Factors); EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases); EC 3.4.25.1 (Proteasome Endopeptidase Complex)
[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:170503
[St] Status:MEDLINE
[do] DOI:10.18632/oncotarget.15804


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[PMID]:29361617
[Au] Autor:Akazawa H
[Ad] Endereço:Dept. of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo.
[Ti] Título:[Cardiotoxicity of Cancer Chemotherapy - Mechanisms and Therapeutic Approach].
[So] Source:Gan To Kagaku Ryoho;44(13):2058-2063, 2017 Dec.
[Is] ISSN:0385-0684
[Cp] País de publicação:Japan
[La] Idioma:jpn
[Ab] Resumo:Recent progress in cancer chemotherapy has improved the long-term outcome for cancer patients. Under such circumstances, it is increasingly of clinical importance to manage the cardiovascular complications, which are related to both cancer itself and adverse effects of cancer therapies. Among the most concerning as cardiovascular complications of cancer therapies is chemotherapy-induced cardiotoxicity or chemotherapy-related cardiac dysfunction(CTRCD). CTRCD has been intuitively classified according to the extent of structural abnormalities and degree of reversibility; type 1 is irreversible and dose-dependent with structural abnormalities, and type 2 is reversible after cessation of treatment and dose-independent without structural abnormalities. An example of drugs causing type 1 and 2 CTRCD is anthracyclines and trastuzumab, respectively, although both drugs are likely to induce cardiotoxicity through a combined action. In addition, there is growing awareness that CTRCD is also caused by anti-VEGF inhibitors and tyrosine kinase inhibitors(TKIs), particularly in patients with cardiovascular comorbidities and risk factors. Interdisciplinary collaboration between oncology and cardiology specialists will contribute to the solution of unmet needs to elucidate epidemiologic and pathophysiologic aspects of CTRCD and to establish diagnostic strategies with risk prediction and evidence-based therapeutic strategies against CTRCD in cancer patients and cancer survivors.
[Mh] Termos MeSH primário: Antraciclinas/efeitos adversos
Antineoplásicos/efeitos adversos
Neoplasias/tratamento farmacológico
[Mh] Termos MeSH secundário: Antraciclinas/uso terapêutico
Antineoplásicos/uso terapêutico
Cardiotoxicidade
Seres Humanos
Complexo de Endopeptidases do Proteassoma/metabolismo
Inibidores de Proteassoma/efeitos adversos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anthracyclines); 0 (Antineoplastic Agents); 0 (Proteasome Inhibitors); EC 3.4.25.1 (Proteasome Endopeptidase Complex)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180302
[Lr] Data última revisão:
180302
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180124
[St] Status:MEDLINE


  4 / 17058 MEDLINE  
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[PMID]:29339252
[Au] Autor:Richy N; Sarraf D; Maréchal X; Janmamode N; Le Guével R; Genin E; Reboud-Ravaux M; Vidal J
[Ad] Endereço:Université Rennes 1, Institut des Sciences Chimiques de Rennes, CNRS UMR 6226, Bâtiment 10A, Campus de Beaulieu, 35042 Rennes, Cedex, France.
[Ti] Título:Structure-based design of human immuno- and constitutive proteasomes inhibitors.
[So] Source:Eur J Med Chem;145:570-587, 2018 Feb 10.
[Is] ISSN:1768-3254
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:Starting from the X-ray structure of our previous tripeptidic linear mimics of TMC-95A in complex with yeast 20S proteasome, we introduced new structural features to induce a differential inhibition between human constitutive and immunoproteasome 20S particles. Libraries of 24 tripeptidic and 6 dipeptidic derivatives were synthesized. The optimized preparation of 3-hydroxyoxindolyl alanine residues from tryptophan and their incorporation in peptides were described. Several potent inhibitors of human constitutive proteasome and immunoproteasome acting at the nanomolar level (IC = 7.1 nM against the chymotrypsin-like activity for the best inhibitor) were obtained. A cytotoxic effect at the submicromolar level was observed against 6 human cancer cell lines.
[Mh] Termos MeSH primário: Antineoplásicos/farmacologia
Desenho de Drogas
Complexo de Endopeptidases do Proteassoma/metabolismo
Inibidores de Proteassoma/farmacologia
[Mh] Termos MeSH secundário: Antineoplásicos/síntese química
Antineoplásicos/química
Linhagem Celular Tumoral
Proliferação Celular/efeitos dos fármacos
Relação Dose-Resposta a Droga
Ensaios de Seleção de Medicamentos Antitumorais
Fibroblastos/efeitos dos fármacos
Seres Humanos
Estrutura Molecular
Inibidores de Proteassoma/síntese química
Inibidores de Proteassoma/química
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Proteasome Inhibitors); EC 3.4.25.1 (Proteasome Endopeptidase Complex)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180302
[Lr] Data última revisão:
180302
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180118
[St] Status:MEDLINE


  5 / 17058 MEDLINE  
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[PMID]:28454724
[Au] Autor:Nagarajan S; Vohra T; Loffing J; Faresse N
[Ad] Endereço:Institute of Anatomy, University of Zurich, 8057 Zurich, Switzerland; National Center of Competence in Research "Kidney.CH", Switzerland.
[Ti] Título:Protein Phosphatase 1α enhances renal aldosterone signaling via mineralocorticoid receptor stabilization.
[So] Source:Mol Cell Endocrinol;450:74-82, 2017 Jul 15.
[Is] ISSN:1872-8057
[Cp] País de publicação:Ireland
[La] Idioma:eng
[Ab] Resumo:Stimulation of the mineralocorticoid receptor (MR) by aldosterone controls several physiological parameters including blood pressure, inflammation or metabolism. We previously showed that MR turnover constitutes a crucial regulatory step in the responses of renal epithelial cells to aldosterone. Here, we identified Protein Phosphatase 1 alpha (PP1α), as a novel cytoplasmic binding partner of MR that promotes the receptor activity. The RT-PCR expression mapping of PP1α reveals a high expression in the kidney, particularly in the distal part of the nephron. At the molecular level, we demonstrate that PP1α inhibits the ubiquitin ligase Mdm2 by dephosphorylation, preventing its interaction with MR. This results in the accumulation of the receptor due to reduction of its proteasomal degradation and consequently a greater aldosterone-induced Na uptake by renal cells. Thus, our findings describe an original mechanism involving a phosphatase in the regulation of aldosterone signaling and provide new and important insights into the molecular mechanism underlying the MR turnover.
[Mh] Termos MeSH primário: Aldosterona/metabolismo
Rim/metabolismo
Proteína Fosfatase 1/metabolismo
Receptores de Mineralocorticoides/metabolismo
Transdução de Sinais
[Mh] Termos MeSH secundário: Animais
Linhagem Celular
Células Epiteliais/efeitos dos fármacos
Células Epiteliais/metabolismo
Células HEK293
Seres Humanos
Camundongos Endogâmicos C57BL
Complexo de Endopeptidases do Proteassoma/metabolismo
Ligação Proteica/efeitos dos fármacos
Domínios Proteicos
Estabilidade Proteica/efeitos dos fármacos
Proteólise/efeitos dos fármacos
Proteínas Proto-Oncogênicas c-mdm2/metabolismo
Receptores de Mineralocorticoides/química
Transdução de Sinais/efeitos dos fármacos
Sódio/metabolismo
Transcrição Genética/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Receptors, Mineralocorticoid); 4964P6T9RB (Aldosterone); 9NEZ333N27 (Sodium); EC 2.3.2.27 (Proto-Oncogene Proteins c-mdm2); EC 3.1.3.16 (Protein Phosphatase 1); EC 3.4.25.1 (Proteasome Endopeptidase Complex)
[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:170430
[St] Status:MEDLINE


  6 / 17058 MEDLINE  
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[PMID]:29355526
[Au] Autor:Bosc E; Nastri J; Lefort V; Valli M; Contiguiba F; Pioli R; Furlan M; Bolzani VDS; El Amri C; Reboud-Ravaux M
[Ad] Endereço:Sorbonne Université, UPMC Univ Paris 06-CNRS, IBPS, UMR 8256, Inserm ERL1164, B2A, 7 Quai Saint Bernard, F75005 Paris, France.
[Ti] Título:Piperlongumine and some of its analogs inhibit selectively the human immunoproteasome over the constitutive proteasome.
[So] Source:Biochem Biophys Res Commun;496(3):961-966, 2018 02 12.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The natural small molecule piperlongumine A is toxic selectively to cancer cells in vitro and in vivo. This toxicity has been correlated with cancer cell ROS, DNA damage and apoptotic cell death increases. We demonstrate here a new mechanistic property of piperlongumine: it inhibits selectively human immunoproteasome with no noticeable inhibition of human constitutive proteasome. This result suggests that immunoproteasome inhibition, a mechanism independent of ROS elevation, may also partly play a role in the anticancer effects observed with piperlongumine. Structure-activity relationships of piperlongumine analogs suggest that the lactam (piperidonic) ring of piperlongumine A may be replaced by the linear olefin -NHCO-CH =CH to improve both in vitro inhibitory efficiency against immunoproteasome and cellular toxicity.
[Mh] Termos MeSH primário: Apoptose/imunologia
Dioxolanos/química
Dioxolanos/imunologia
Imunoproteínas/química
Imunoproteínas/imunologia
Complexo de Endopeptidases do Proteassoma/química
Complexo de Endopeptidases do Proteassoma/imunologia
[Mh] Termos MeSH secundário: Apoptose/efeitos dos fármacos
Dioxolanos/administração & dosagem
Relação Dose-Resposta a Droga
Avaliação Pré-Clínica de Medicamentos
Células HeLa
Seres Humanos
Ligação Proteica
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Dioxolanes); 0 (Immunoproteins); EC 3.4.25.1 (Proteasome Endopeptidase Complex); HN39MC8KIO (piperlonguminine)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180222
[Lr] Data última revisão:
180222
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180123
[St] Status:MEDLINE


  7 / 17058 MEDLINE  
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[PMID]:29269255
[Au] Autor:Bakas NA; Schultz CR; Yco LP; Roberts CC; Chang CA; Bachmann AS; Pirrung MC
[Ad] Endereço:Department of Chemistry, University of California, Riverside, CA 92521, USA.
[Ti] Título:Immunoproteasome inhibition and bioactivity of thiasyrbactins.
[So] Source:Bioorg Med Chem;26(2):401-412, 2018 01 15.
[Is] ISSN:1464-3391
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:A family of macrodilactam natural products, the syrbactins, are known proteasome inhibitors. A small group of syrbactin analogs was prepared with a sulfur-for-carbon substitution to enhance synthetic accessibility and facilitate modulation of their solubility. Two of these compounds surprisingly proved to be inhibitors of the trypsin-like catalytic site, including of the immunoproteasome. Their bound and free conformations suggest special properties of the thiasyrbactin ring are responsible for this unusual preference, which may be exploited to develop drug-like immunoproteasome inhibitors. These compounds show greater selectivity than earlier compounds used to infer phenotypes of immunoproteasome inhibition, like ONX-0914.
[Mh] Termos MeSH primário: Produtos Biológicos/farmacologia
Lactamas/farmacologia
Complexo de Endopeptidases do Proteassoma/metabolismo
Inibidores de Proteassoma/farmacologia
[Mh] Termos MeSH secundário: Produtos Biológicos/síntese química
Produtos Biológicos/química
Linhagem Celular Tumoral
Sobrevivência Celular/efeitos dos fármacos
Relação Dose-Resposta a Droga
Seres Humanos
Lactamas/síntese química
Lactamas/química
Estrutura Molecular
Inibidores de Proteassoma/síntese química
Inibidores de Proteassoma/química
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T; RESEARCH SUPPORT, U.S. GOV'T, NON-P.H.S.
[Nm] Nome de substância:
0 (Biological Products); 0 (Lactams); 0 (Proteasome Inhibitors); EC 3.4.25.1 (Proteasome Endopeptidase Complex)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180220
[Lr] Data última revisão:
180220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171223
[St] Status:MEDLINE


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[PMID]:29348419
[Au] Autor:Wentzel C; Delvendahl I; Sydlik S; Georgiev O; Müller M
[Ad] Endereço:Institute of Molecular Life Sciences, University of Zurich, Winterthurerstrasse 190, 8057, Zurich, Switzerland.
[Ti] Título:Dysbindin links presynaptic proteasome function to homeostatic recruitment of low release probability vesicles.
[So] Source:Nat Commun;9(1):267, 2018 01 18.
[Is] ISSN:2041-1723
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Here we explore the relationship between presynaptic homeostatic plasticity and proteasome function at the Drosophila neuromuscular junction. First, we demonstrate that the induction of homeostatic plasticity is blocked after presynaptic proteasome perturbation. Proteasome inhibition potentiates release under baseline conditions but not during homeostatic plasticity, suggesting that proteasomal degradation and homeostatic plasticity modulate a common pool of vesicles. The vesicles that are regulated by proteasome function and recruited during homeostatic plasticity are highly EGTA sensitive, implying looser Ca influx-release coupling. Similar to homeostatic plasticity, proteasome perturbation enhances presynaptic Ca influx, readily-releasable vesicle pool size, and does not potentiate release after loss of specific homeostatic plasticity genes, including the schizophrenia-susceptibility gene dysbindin. Finally, we provide genetic evidence that Dysbindin levels regulate the access to EGTA-sensitive vesicles. Together, our data suggest that presynaptic protein degradation opposes the release of low-release probability vesicles that are potentiated during homeostatic plasticity and whose access is controlled by dysbindin.
[Mh] Termos MeSH primário: Disbindina/metabolismo
Junção Neuromuscular/metabolismo
Plasticidade Neuronal
Complexo de Endopeptidases do Proteassoma/metabolismo
Vesículas Sinápticas/fisiologia
[Mh] Termos MeSH secundário: Animais
Animais Geneticamente Modificados
Cálcio/metabolismo
Drosophila
Proteínas de Drosophila/metabolismo
Ácido Egtázico
Homeostase
Proteínas rab3 de Ligação ao GTP/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Drosophila Proteins); 0 (Dysbindin); 0 (RIM protein, Drosophila); 526U7A2651 (Egtazic Acid); EC 3.4.25.1 (Proteasome Endopeptidase Complex); EC 3.6.5.2 (rab3 GTP-Binding Proteins); SY7Q814VUP (Calcium)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180215
[Lr] Data última revisão:
180215
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180120
[St] Status:MEDLINE
[do] DOI:10.1038/s41467-017-02494-0


  9 / 17058 MEDLINE  
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[PMID]:28740232
[Au] Autor:Cha-Molstad H; Yu JE; Feng Z; Lee SH; Kim JG; Yang P; Han B; Sung KW; Yoo YD; Hwang J; McGuire T; Shim SM; Song HD; Ganipisetti S; Wang N; Jang JM; Lee MJ; Kim SJ; Lee KH; Hong JT; Ciechanover A; Mook-Jung I; Kim KP; Xie XQ; Kwon YT; Kim BY
[Ad] Endereço:World Class Institute, Anticancer Agents Research Center, Korea Research Institute of Bioscience and Biotechnology, Ochang, Cheongwon, 28116, Korea.
[Ti] Título:p62/SQSTM1/Sequestosome-1 is an N-recognin of the N-end rule pathway which modulates autophagosome biogenesis.
[So] Source:Nat Commun;8(1):102, 2017 07 24.
[Is] ISSN:2041-1723
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Macroautophagy mediates the selective degradation of proteins and non-proteinaceous cellular constituents. Here, we show that the N-end rule pathway modulates macroautophagy. In this mechanism, the autophagic adapter p62/SQSTM1/Sequestosome-1 is an N-recognin that binds type-1 and type-2 N-terminal degrons (N-degrons), including arginine (Nt-Arg). Both types of N-degrons bind its ZZ domain. By employing three-dimensional modeling, we developed synthetic ligands to p62 ZZ domain. The binding of Nt-Arg and synthetic ligands to ZZ domain facilitates disulfide bond-linked aggregation of p62 and p62 interaction with LC3, leading to the delivery of p62 and its cargoes to the autophagosome. Upon binding to its ligand, p62 acts as a modulator of macroautophagy, inducing autophagosome biogenesis. Through these dual functions, cells can activate p62 and induce selective autophagy upon the accumulation of autophagic cargoes. We also propose that p62 mediates the crosstalk between the ubiquitin-proteasome system and autophagy through its binding Nt-Arg and other N-degrons.Soluble misfolded proteins that fail to be degraded by the ubiquitin proteasome system (UPS) are redirected to autophagy via specific adaptors, such as p62. Here the authors show that p62 recognises N-degrons in these proteins, acting as a N-recognin from the proteolytic N-end rule pathway, and targets these cargos to autophagosomal degradation.
[Mh] Termos MeSH primário: Autofagossomos/metabolismo
Proteínas Associadas aos Microtúbulos/metabolismo
Proteína Sequestossoma-1/metabolismo
Transdução de Sinais
[Mh] Termos MeSH secundário: Proteínas Adaptadoras de Transdução de Sinal
Animais
Arginina/metabolismo
Autofagia
Sítios de Ligação
Western Blotting
Células Cultivadas
Células HEK293
Células HeLa
Seres Humanos
Camundongos Knockout
Microscopia Confocal
Modelos Moleculares
Complexo de Endopeptidases do Proteassoma/metabolismo
Ligação Proteica
Domínios Proteicos
Proteólise
Proteína Sequestossoma-1/química
Proteína Sequestossoma-1/genética
Ubiquitina-Proteína Ligases/química
Ubiquitina-Proteína Ligases/genética
Ubiquitina-Proteína Ligases/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Adaptor Proteins, Signal Transducing); 0 (Microtubule-Associated Proteins); 0 (Sequestosome-1 Protein); 0 (light chain 3, human); 94ZLA3W45F (Arginine); EC 2.3.2.27 (UBR1 protein, mouse); EC 2.3.2.27 (Ubiquitin-Protein Ligases); EC 3.4.25.1 (Proteasome Endopeptidase Complex)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:180216
[Lr] Data última revisão:
180216
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170726
[St] Status:MEDLINE
[do] DOI:10.1038/s41467-017-00085-7


  10 / 17058 MEDLINE  
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[PMID]:29305860
[Au] Autor:Zhong X; Lee HN; Surh YJ
[Ad] Endereço:Tumor Microenvironment Global Core Research Center, College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea.
[Ti] Título:RvD1 inhibits TNFα-induced c-Myc expression in normal intestinal epithelial cells and destabilizes hyper-expressed c-Myc in colon cancer cells.
[So] Source:Biochem Biophys Res Commun;496(2):316-323, 2018 02 05.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Inflammatory bowel diseases, including ulcerative colitis and Crohn's disease, are persistent disorders that lead to development of colitis-associated cancer (CAC). Facilitated resolution of colitis has been addressed as a novel therapeutic strategy to control development of CAC. Resolvin D1 (RvD1) is an endogenous lipid mediator that is generated from docosahexaenoic acid during the resolution of inflammation. Although the pro-resolving effects of RvDs have been extensively investigated and well defined, the role for RvD1 in CAC remains largely unknown. In this study, we found that RvD1 inhibited the expression of c-Myc in normal colon cells stimulated with tumor necrosis factor-α (TNFα) and also in colon cancer cells. The suppression of TNFα-induced upregulation of c-Myc in normal cells was mediated through attenuation of NF-κB signaling. Notably, RvD1 destabilized the constitutively overexpressed c-Myc protein in HCT 116 human colon cancer cells by stimulating its ubiquitination and subsequent proteasomal degradation. Further, we revealed that RvD1 stimulated c-Myc degradation through direct interaction with the ALX/FPR2 receptor. This interaction resulted in inhibition of activation of extracellular signal-regulated kinase, thereby attenuating phosphorylation-dependent stabilization of c-Myc.
[Mh] Termos MeSH primário: Anti-Inflamatórios/farmacologia
Antineoplásicos/farmacologia
Neoplasias do Colo/prevenção & controle
Proteínas de Ligação a DNA/genética
Ácidos Docosa-Hexaenoicos/farmacologia
Regulação Neoplásica da Expressão Gênica
Fatores de Transcrição/genética
Fator de Necrose Tumoral alfa/antagonistas & inibidores
[Mh] Termos MeSH secundário: Proteínas Adaptadoras de Transdução de Sinal/genética
Proteínas Adaptadoras de Transdução de Sinal/metabolismo
Animais
Azoximetano
Carcinógenos
Neoplasias do Colo/induzido quimicamente
Neoplasias do Colo/genética
Neoplasias do Colo/patologia
Proteínas de Ligação a DNA/antagonistas & inibidores
Proteínas de Ligação a DNA/metabolismo
Células HCT116
Seres Humanos
Camundongos
Camundongos Endogâmicos C57BL
NF-kappa B/genética
NF-kappa B/metabolismo
Fosforilação/efeitos dos fármacos
Complexo de Endopeptidases do Proteassoma/efeitos dos fármacos
Complexo de Endopeptidases do Proteassoma/metabolismo
Proteólise/efeitos dos fármacos
Receptores de Formil Peptídeo/genética
Receptores de Formil Peptídeo/metabolismo
Receptores de Lipoxinas/genética
Receptores de Lipoxinas/metabolismo
Transdução de Sinais
Fatores de Transcrição/antagonistas & inibidores
Fatores de Transcrição/metabolismo
Fator de Necrose Tumoral alfa/farmacologia
Ubiquitinação
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Adaptor Proteins, Signal Transducing); 0 (Anti-Inflammatory Agents); 0 (Antineoplastic Agents); 0 (Carcinogens); 0 (DNA-Binding Proteins); 0 (FPR2 protein, human); 0 (HSH2D protein, human); 0 (MYCBP protein, human); 0 (NF-kappa B); 0 (Receptors, Formyl Peptide); 0 (Receptors, Lipoxin); 0 (Transcription Factors); 0 (Tumor Necrosis Factor-alpha); 0 (resolvin D1); 25167-62-8 (Docosahexaenoic Acids); EC 3.4.25.1 (Proteasome Endopeptidase Complex); MO0N1J0SEN (Azoxymethane)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180214
[Lr] Data última revisão:
180214
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180107
[St] Status:MEDLINE



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