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Pesquisa : D12.776.543.990.300 [Categoria DeCS]
Referências encontradas : 308 [refinar]
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[PMID]:28962860
[Au] Autor:Zhang N; Zhang L
[Ad] Endereço:MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100176, China.
[Ti] Título:Key components of COPI and COPII machineries are required for chikungunya virus replication.
[So] Source:Biochem Biophys Res Commun;493(3):1190-1196, 2017 Nov 25.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The infection of CHIKV is associated with cellular membranes; however whether early secretory pathways are involved in CHIKV replication remains unclear. In the present study, we have provided initial evidences that CHIKV requires both COPI and COPII for its replication. Small interfering RNAs against COPI components, including coatomer, ARFs or GBF1, suppress CHIKV replication. Moreover, CHIKV infection is abolished by the presence of ARF1 inhibitor brefeldin A or GBF1 inhibitor golgicide A. In addition, perturbation of COPII by silencing key components of COPII pathways leads to a reduction in CHIKV replication. Collectively, these observations demonstrate the importance of functional secretory pathways in the infectivity of CHIKV.
[Mh] Termos MeSH primário: Vírus Chikungunya/fisiologia
Complexo I de Proteína do Envoltório/metabolismo
Proteínas Virais/metabolismo
Replicação Viral/fisiologia
[Mh] Termos MeSH secundário: Fator 1 de Ribosilação do ADP/genética
Fator 1 de Ribosilação do ADP/metabolismo
Brefeldina A/farmacologia
Vírus Chikungunya/patogenicidade
Complexo I de Proteína do Envoltório/genética
Fatores de Troca do Nucleotídeo Guanina/genética
Fatores de Troca do Nucleotídeo Guanina/metabolismo
Células HeLa
Seres Humanos
Piridinas/farmacologia
Quinolinas/farmacologia
RNA Interferente Pequeno
Proteínas Virais/genética
Replicação Viral/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Coat Protein Complex I); 0 (Guanine Nucleotide Exchange Factors); 0 (Pyridines); 0 (Quinolines); 0 (RNA, Small Interfering); 0 (Viral Proteins); 0 (golgicide A); 20350-15-6 (Brefeldin A); EC 3.6.5.2 (ADP-Ribosylation Factor 1)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171027
[Lr] Data última revisão:
171027
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171001
[St] Status:MEDLINE


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[PMID]:28428254
[Au] Autor:Bottanelli F; Kilian N; Ernst AM; Rivera-Molina F; Schroeder LK; Kromann EB; Lessard MD; Erdmann RS; Schepartz A; Baddeley D; Bewersdorf J; Toomre D; Rothman JE
[Ad] Endereço:Department of Cell Biology, Yale University School of Medicine, New Haven, CT 06520.
[Ti] Título:A novel physiological role for ARF1 in the formation of bidirectional tubules from the Golgi.
[So] Source:Mol Biol Cell;28(12):1676-1687, 2017 Jun 15.
[Is] ISSN:1939-4586
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Capitalizing on CRISPR/Cas9 gene-editing techniques and super-resolution nanoscopy, we explore the role of the small GTPase ARF1 in mediating transport steps at the Golgi. Besides its well-established role in generating COPI vesicles, we find that ARF1 is also involved in the formation of long (∼3 µm), thin (∼110 nm diameter) tubular carriers. The anterograde and retrograde tubular carriers are both largely free of the classical Golgi coat proteins coatomer (COPI) and clathrin. Instead, they contain ARF1 along their entire length at a density estimated to be in the range of close packing. Experiments using a mutant form of ARF1 affecting GTP hydrolysis suggest that ARF1[GTP] is functionally required for the tubules to form. Dynamic confocal and stimulated emission depletion imaging shows that ARF1-rich tubular compartments fall into two distinct classes containing 1) anterograde cargoes and clathrin clusters or 2) retrograde cargoes and coatomer clusters.
[Mh] Termos MeSH primário: Fator 1 de Ribosilação do ADP/fisiologia
Complexo de Golgi/fisiologia
[Mh] Termos MeSH secundário: Fator 1 de Ribosilação do ADP/genética
Fator 1 de Ribosilação do ADP/metabolismo
Vesículas Revestidas pelo Complexo de Proteína do Envoltório/metabolismo
Clatrina/metabolismo
Complexo I de Proteína do Envoltório/metabolismo
GTP Fosfo-Hidrolases/metabolismo
Complexo de Golgi/metabolismo
Guanosina Trifosfato/metabolismo
Células HeLa
Seres Humanos
Hidrólise
Membranas Intracelulares/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Clathrin); 0 (Coat Protein Complex I); 86-01-1 (Guanosine Triphosphate); EC 3.6.1.- (GTP Phosphohydrolases); EC 3.6.5.2 (ADP-Ribosylation Factor 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:170422
[St] Status:MEDLINE
[do] DOI:10.1091/mbc.E16-12-0863


  3 / 308 MEDLINE  
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[PMID]:28003365
[Au] Autor:Chen J; Wu X; Yao L; Yan L; Zhang L; Qiu J; Liu X; Jia S; Meng A
[Ad] Endereço:From the Laboratory of Molecular Developmental Biology, State Key Laboratory of Membrane Biology, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
[Ti] Título:Impairment of Cargo Transportation Caused by Mutation Disrupts Vascular Integrity and Causes Hemorrhage in Zebrafish Embryos.
[So] Source:J Biol Chem;292(6):2315-2327, 2017 Feb 10.
[Is] ISSN:1083-351X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:ADP-ribosylation factor GTPases are activated by guanine nucleotide exchange factors including Gbf1 (Golgi brefeldin A-resistant factor 1) and play important roles in regulating organelle structure and cargo-selective vesicle trafficking. However, the developmental role of Gbf1 in vertebrates remains elusive. In this study, we report the zebrafish mutant line that arises from -ethyl- -nitrosourea (ENU)-mediated mutagenesis and is characterized by prominent intracerebral and trunk hemorrhage. The mutant embryos develop hemorrhage accompanied by fewer pigments and shorter caudal fin at day 2 of development. The hemorrhage phenotype is caused by vascular breakage in a cell autonomous fashion. Positional cloning identifies a T → G nucleotide substitution in the 23rd exon of the locus, resulting in a leucine → arginine substitution (L1246R) in the HDS2 domain. The mutant phenotype is mimicked by knockouts and morphants, suggesting a nature of loss of function. Experimental results in mammalian cells show that the mutant form Gbf1(L1246R) is unable to be recruited to the Golgi apparatus and fails to activate Arf1 for recruiting COPI complex. The hemorrhage in mutants can be prevented partially and temporally by treating with the endoplasmic reticulum stress/apoptosis inhibitor tauroursodeoxycholic acid or by knocking down the proapoptotic gene Therefore, endothelial endoplasmic reticulum stress and subsequent apoptosis induced by deficiency may account for the vascular collapse and hemorrhage.
[Mh] Termos MeSH primário: Vasos Sanguíneos/fisiopatologia
Fatores de Troca do Nucleotídeo Guanina/genética
Hemorragia/etiologia
Mutação
Peixe-Zebra/embriologia
[Mh] Termos MeSH secundário: Animais
Complexo I de Proteína do Envoltório/metabolismo
Complexo de Golgi/metabolismo
Fatores de Troca do Nucleotídeo Guanina/metabolismo
Transporte Proteico
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Coat Protein Complex I); 0 (Guanine Nucleotide Exchange Factors)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170704
[Lr] Data última revisão:
170704
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161223
[St] Status:MEDLINE
[do] DOI:10.1074/jbc.M116.767608


  4 / 308 MEDLINE  
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[PMID]:28003315
[Au] Autor:Li C; Luo X; Zhao S; Siu GK; Liang Y; Chan HC; Satoh A; Yu SS
[Ad] Endereço:Department of Anatomy, Histology and Developmental Biology, School of Basic Medical Sciences, Health Science Centre, Shenzhen University, Shenzhen, China.
[Ti] Título:COPI-TRAPPII activates Rab18 and regulates its lipid droplet association.
[So] Source:EMBO J;36(4):441-457, 2017 Feb 15.
[Is] ISSN:1460-2075
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The transport protein particle (TRAPP) was initially identified as a vesicle tethering factor in yeast and as a guanine nucleotide exchange factor (GEF) for Ypt1/Rab1. In mammals, structures and functions of various TRAPP complexes are beginning to be understood. We found that mammalian TRAPPII was a GEF for both Rab18 and Rab1. Inactivation of TRAPPII-specific subunits by various methods including siRNA depletion and CRISPR-Cas9-mediated deletion reduced lipolysis and resulted in aberrantly large lipid droplets. Recruitment of Rab18 onto lipid droplet (LD) surface was defective in TRAPPII-deleted cells, but the localization of Rab1 on Golgi was not affected. COPI regulates LD homeostasis. We found that the previously documented interaction between TRAPPII and COPI was also required for the recruitment of Rab18 to the LD We hypothesize that the interaction between COPI and TRAPPII helps bring TRAPPII onto LD surface, and TRAPPII, in turn, activates Rab18 and recruits it on the LD surface to facilitate its functions in LD homeostasis.
[Mh] Termos MeSH primário: Complexo I de Proteína do Envoltório/metabolismo
Gotículas Lipídicas/metabolismo
Proteínas de Transporte Vesicular/metabolismo
Proteínas rab de Ligação ao GTP/metabolismo
[Mh] Termos MeSH secundário: Linhagem Celular
Técnicas de Silenciamento de Genes
Técnicas de Inativação de Genes
Seres Humanos
Lipólise
Proteínas de Transporte Vesicular/genética
Proteínas rab1 de Ligação ao GTP/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Coat Protein Complex I); 0 (RAB18 protein, human); 0 (Vesicular Transport Proteins); 0 (transport protein particle, TRAPP); EC 3.6.5.2 (rab GTP-Binding Proteins); EC 3.6.5.2 (rab1 GTP-Binding Proteins)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170713
[Lr] Data última revisão:
170713
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161223
[St] Status:MEDLINE
[do] DOI:10.15252/embj.201694866


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[PMID]:27680705
[Au] Autor:Singh SR; Zeng X; Zhao J; Liu Y; Hou G; Liu H; Hou SX
[Ad] Endereço:The Basic Research Laboratory, National Cancer Institute at Frederick, National Institutes of Health, Frederick, Maryland 21702, USA.
[Ti] Título:The lipolysis pathway sustains normal and transformed stem cells in adult Drosophila.
[So] Source:Nature;538(7623):109-113, 2016 Oct 06.
[Is] ISSN:1476-4687
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Cancer stem cells (CSCs) may be responsible for tumour dormancy, relapse and the eventual death of most cancer patients. In addition, these cells are usually resistant to cytotoxic conditions. However, very little is known about the biology behind this resistance to therapeutics. Here we investigated stem-cell death in the digestive system of adult Drosophila melanogaster. We found that knockdown of the coat protein complex I (COPI)-Arf79F (also known as Arf1) complex selectively killed normal and transformed stem cells through necrosis, by attenuating the lipolysis pathway, but spared differentiated cells. The dying stem cells were engulfed by neighbouring differentiated cells through a draper-myoblast city-Rac1-basket (also known as JNK)-dependent autophagy pathway. Furthermore, Arf1 inhibitors reduced CSCs in human cancer cell lines. Thus, normal or cancer stem cells may rely primarily on lipid reserves for energy, in such a way that blocking lipolysis starves them to death. This finding may lead to new therapies that could help to eliminate CSCs in human cancers.
[Mh] Termos MeSH primário: Transformação Celular Neoplásica/metabolismo
Transformação Celular Neoplásica/patologia
Drosophila melanogaster/citologia
Drosophila melanogaster/metabolismo
Lipólise/fisiologia
Células-Tronco Neoplásicas/metabolismo
Células-Tronco Neoplásicas/patologia
[Mh] Termos MeSH secundário: Fator 1 de Ribosilação do ADP/antagonistas & inibidores
Fator 1 de Ribosilação do ADP/deficiência
Animais
Apoptose
Autofagia
Diferenciação Celular
Linhagem Celular Tumoral
Proliferação Celular
Sobrevivência Celular/efeitos dos fármacos
Transformação Celular Neoplásica/efeitos dos fármacos
Complexo I de Proteína do Envoltório/deficiência
Proteínas de Drosophila/metabolismo
Drosophila melanogaster/genética
Resistência a Medicamentos Antineoplásicos/efeitos dos fármacos
Metabolismo Energético
Enterócitos/citologia
Feminino
Trato Gastrointestinal/patologia
Seres Humanos
Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo
Lipólise/efeitos dos fármacos
Sistema de Sinalização das MAP Quinases
Masculino
Proteínas de Membrana/metabolismo
Necrose/induzido quimicamente
Células-Tronco Neoplásicas/efeitos dos fármacos
Fagocitose
Proteínas rac de Ligação ao GTP/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Coat Protein Complex I); 0 (Draper protein, Drosophila); 0 (Drosophila Proteins); 0 (Membrane Proteins); EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases); EC 3.6.5.2 (ADP-Ribosylation Factor 1); EC 3.6.5.2 (rac GTP-Binding Proteins)
[Em] Mês de entrada:1703
[Cu] Atualização por classe:170307
[Lr] Data última revisão:
170307
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160930
[St] Status:MEDLINE
[do] DOI:10.1038/nature19788


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[PMID]:27476655
[Au] Autor:Izumi K; Brett M; Nishi E; Drunat S; Tan ES; Fujiki K; Lebon S; Cham B; Masuda K; Arakawa M; Jacquinet A; Yamazumi Y; Chen ST; Verloes A; Okada Y; Katou Y; Nakamura T; Akiyama T; Gressens P; Foo R; Passemard S; Tan EC; El Ghouzzi V; Shirahige K
[Ad] Endereço:Research Center for Epigenetic Disease, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Tokyo 113-0032, Japan; Division of Medical Genetics, Nagano Children's Hospital, Azumino 399-8205, Japan; Division of Human Genetics, The Children's Hospital of Philadelphia, Philadelphi
[Ti] Título:ARCN1 Mutations Cause a Recognizable Craniofacial Syndrome Due to COPI-Mediated Transport Defects.
[So] Source:Am J Hum Genet;99(2):451-9, 2016 Aug 04.
[Is] ISSN:1537-6605
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Cellular homeostasis is maintained by the highly organized cooperation of intracellular trafficking systems, including COPI, COPII, and clathrin complexes. COPI is a coatomer protein complex responsible for intracellular protein transport between the endoplasmic reticulum and the Golgi apparatus. The importance of such intracellular transport mechanisms is underscored by the various disorders, including skeletal disorders such as cranio-lenticulo-sutural dysplasia and osteogenesis imperfect, caused by mutations in the COPII coatomer complex. In this article, we report a clinically recognizable craniofacial disorder characterized by facial dysmorphisms, severe micrognathia, rhizomelic shortening, microcephalic dwarfism, and mild developmental delay due to loss-of-function heterozygous mutations in ARCN1, which encodes the coatomer subunit delta of COPI. ARCN1 mutant cell lines were revealed to have endoplasmic reticulum stress, suggesting the involvement of ER stress response in the pathogenesis of this disorder. Given that ARCN1 deficiency causes defective type I collagen transport, reduction of collagen secretion represents the likely mechanism underlying the skeletal phenotype that characterizes this condition. Our findings demonstrate the importance of COPI-mediated transport in human development, including skeletogenesis and brain growth.
[Mh] Termos MeSH primário: Complexo I de Proteína do Envoltório/metabolismo
Proteína Coatomer/genética
Anormalidades Craniofaciais/genética
Mutação
[Mh] Termos MeSH secundário: Adulto
Proteína Coatomer/metabolismo
Colágeno/metabolismo
Estresse do Retículo Endoplasmático
Heterozigoto
Seres Humanos
Lactente
Recém-Nascido
Masculino
Síndrome
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Coat Protein Complex I); 0 (Coatomer Protein); 9007-34-5 (Collagen)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170509
[Lr] Data última revisão:
170509
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160802
[St] Status:MEDLINE


  7 / 308 MEDLINE  
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[PMID]:27445311
[Au] Autor:Ishii M; Suda Y; Kurokawa K; Nakano A
[Ad] Endereço:Live Cell Super-Resolution Imaging Research Team, RIKEN Center for Advanced Photonics, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan Department of Biological Sciences, Graduate School of Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
[Ti] Título:COPI is essential for Golgi cisternal maturation and dynamics.
[So] Source:J Cell Sci;129(17):3251-61, 2016 Sep 01.
[Is] ISSN:1477-9137
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Proteins synthesized in the endoplasmic reticulum (ER) are transported to the Golgi and then sorted to their destinations. For their passage through the Golgi, one widely accepted mechanism is cisternal maturation. Cisternal maturation is fulfilled by the retrograde transport of Golgi-resident proteins from later to earlier cisternae, and candidate carriers for this retrograde transport are coat protein complex I (COPI)-coated vesicles. We examined the COPI function in cisternal maturation directly by 4D observation of the transmembrane Golgi-resident proteins in living yeast cells. COPI temperature-sensitive mutants and induced degradation of COPI proteins were used to knockdown COPI function. For both methods, inactivation of COPI subunits Ret1 and Sec21 markedly impaired the transition from cis to medial and to trans cisternae. Furthermore, the movement of cisternae within the cytoplasm was severely restricted when COPI subunits were depleted. Our results demonstrate the essential roles of COPI proteins in retrograde trafficking of the Golgi-resident proteins and dynamics of the Golgi cisternae.
[Mh] Termos MeSH primário: Complexo I de Proteína do Envoltório/metabolismo
Complexo de Golgi/metabolismo
Saccharomyces cerevisiae/metabolismo
[Mh] Termos MeSH secundário: Complexo de Golgi/efeitos dos fármacos
Ácidos Indolacéticos/farmacologia
Proteínas de Membrana/metabolismo
Mutação/genética
Proteólise/efeitos dos fármacos
Saccharomyces cerevisiae/efeitos dos fármacos
Temperatura Ambiente
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Coat Protein Complex I); 0 (Indoleacetic Acids); 0 (Membrane Proteins)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170808
[Lr] Data última revisão:
170808
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160723
[St] Status:MEDLINE
[do] DOI:10.1242/jcs.193367


  8 / 308 MEDLINE  
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[PMID]:27369768
[Au] Autor:Ludwig A; Nichols BJ; Sandin S
[Ad] Endereço:School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, 637551 Singapore aludwig@ntu.edu.sg.
[Ti] Título:Architecture of the caveolar coat complex.
[So] Source:J Cell Sci;129(16):3077-83, 2016 Aug 15.
[Is] ISSN:1477-9137
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Caveolae are specialized membrane domains that are crucial for the correct function of endothelial cells, adipocytes and muscle cells. Caveolins and cavins are both required for caveolae formation, and assemble into a large (80S) caveolar coat complex (80S-CCC). The architecture of the 80S-CCC, however, has not been analyzed. Here, we study the 80S-CCC isolated from mammalian cells using negative stain electron microscopy and 3D cryo-electron tomography. We show that the 80S-CCC is a hollow sphere with a diameter of 50-80 nm, and so has the same size and shape as individual caveolar bulbs. This provides strong evidence that the distinctive membrane shape of caveolae is generated by the shape of the 80S-CCC itself. The particle appears to be made up of two layers, an inner coat composed of polygonal units of caveolins that form a polyhedral cage, and an outer filamentous coat composed of cavins. The data suggest that the peripheral cavin coat is aligned along the edges of the inner polyhedral cage, thereby providing a mechanism for the generation of a morphologically stable caveolar coat.
[Mh] Termos MeSH primário: Cavéolas/metabolismo
Complexo I de Proteína do Envoltório/metabolismo
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Cavéolas/ultraestrutura
Complexo I de Proteína do Envoltório/química
Complexo I de Proteína do Envoltório/ultraestrutura
Microscopia Crioeletrônica
Células HeLa
Seres Humanos
Modelos Biológicos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Coat Protein Complex I)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170922
[Lr] Data última revisão:
170922
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160703
[St] Status:MEDLINE
[do] DOI:10.1242/jcs.191262


  9 / 308 MEDLINE  
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[PMID]:27365400
[Au] Autor:Hsiao JJ; Smits MM; Ng BH; Lee J; Wright ME
[Ad] Endereço:From the Department of Molecular Physiology and Biophysics, Carver College of Medicine, Iowa City, Iowa 52242.
[Ti] Título:Discovery Proteomics Identifies a Molecular Link between the Coatomer Protein Complex I and Androgen Receptor-dependent Transcription.
[So] Source:J Biol Chem;291(36):18818-42, 2016 09 02.
[Is] ISSN:1083-351X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Aberrant androgen receptor (AR)-dependent transcription is a hallmark of human prostate cancers. At the molecular level, ligand-mediated AR activation is coordinated through spatial and temporal protein-protein interactions involving AR-interacting proteins, which we designate the "AR-interactome." Despite many years of research, the ligand-sensitive protein complexes involved in ligand-mediated AR activation in prostate tumor cells have not been clearly defined. Here, we describe the development, characterization, and utilization of a novel human LNCaP prostate tumor cell line, N-AR, which stably expresses wild-type AR tagged at its N terminus with the streptavidin-binding peptide epitope (streptavidin-binding peptide-tagged wild-type androgen receptor; SBP-AR). A bioanalytical workflow involving streptavidin chromatography and label-free quantitative mass spectrometry was used to identify SBP-AR and associated ligand-sensitive cytosolic proteins/protein complexes linked to AR activation in prostate tumor cells. Functional studies verified that ligand-sensitive proteins identified in the proteomic screen encoded modulators of AR-mediated transcription, suggesting that these novel proteins were putative SBP-AR-interacting proteins in N-AR cells. This was supported by biochemical associations between recombinant SBP-AR and the ligand-sensitive coatomer protein complex I (COPI) retrograde trafficking complex in vitro Extensive biochemical and molecular experiments showed that the COPI retrograde complex regulates ligand-mediated AR transcriptional activation, which correlated with the mobilization of the Golgi-localized ARA160 coactivator to the nuclear compartment of prostate tumor cells. Collectively, this study provides a bioanalytical strategy to validate the AR-interactome and define novel AR-interacting proteins involved in ligand-mediated AR activation in prostate tumor cells. Moreover, we describe a cellular system to study how compartment-specific AR-interacting proteins influence AR activation and contribute to aberrant AR-dependent transcription that underlies the majority of human prostate cancers.
[Mh] Termos MeSH primário: Núcleo Celular/metabolismo
Complexo I de Proteína do Envoltório/metabolismo
Proteínas de Neoplasias/metabolismo
Neoplasias da Próstata/metabolismo
Receptores Androgênicos/metabolismo
Transcrição Genética
[Mh] Termos MeSH secundário: Transporte Ativo do Núcleo Celular
Linhagem Celular Tumoral
Núcleo Celular/genética
Complexo I de Proteína do Envoltório/genética
Proteínas de Ligação a DNA/genética
Proteínas de Ligação a DNA/metabolismo
Complexo de Golgi/genética
Complexo de Golgi/metabolismo
Seres Humanos
Masculino
Proteínas de Neoplasias/genética
Neoplasias da Próstata/genética
Proteômica
Receptores Androgênicos/genética
Fatores de Transcrição/genética
Fatores de Transcrição/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Coat Protein Complex I); 0 (DNA-Binding Proteins); 0 (Neoplasm Proteins); 0 (Receptors, Androgen); 0 (Transcription Factors); 149954-67-6 (TMF1 protein, human)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:171124
[Lr] Data última revisão:
171124
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160702
[St] Status:MEDLINE
[do] DOI:10.1074/jbc.M116.732313


  10 / 308 MEDLINE  
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[PMID]:27114526
[Au] Autor:Bettayeb K; Hooli BV; Parrado AR; Randolph L; Varotsis D; Aryal S; Gresack J; Tanzi RE; Greengard P; Flajolet M
[Ad] Endereço:Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, NY 10065;
[Ti] Título:Relevance of the COPI complex for Alzheimer's disease progression in vivo.
[So] Source:Proc Natl Acad Sci U S A;113(19):5418-23, 2016 May 10.
[Is] ISSN:1091-6490
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Cellular trafficking and recycling machineries belonging to late secretory compartments have been associated with increased Alzheimer's disease (AD) risk. We have shown that coat protein complex I (COPI)-dependent trafficking, an early step in Golgi-to-endoplasmic reticulum retrograde transport, affects amyloid precursor protein subcellular localization, cell-surface expression, as well as its metabolism. We present here a set of experiments demonstrating that, by targeting subunit δ-COP function, the moderation of the COPI-dependent trafficking in vivo leads to a significant decrease in amyloid plaques in the cortex and hippocampus of neurological 17 mice crossed with the 2xTg AD mouse model. Remarkably, an improvement of the memory impairments was also observed. Importantly, human genetic association studies of different AD cohorts led to the identification of 12 SNPs and 24 mutations located in COPI genes linked to an increased AD risk. These findings further demonstrate in vivo the importance of early trafficking steps in AD pathogenesis and open new clinical perspectives.
[Mh] Termos MeSH primário: Doença de Alzheimer/metabolismo
Encéfalo/metabolismo
Complexo I de Proteína do Envoltório/metabolismo
Progressão da Doença
Placa Amiloide/metabolismo
Frações Subcelulares/metabolismo
[Mh] Termos MeSH secundário: Animais
Masculino
Camundongos
Camundongos Endogâmicos C57BL
Transporte Proteico/fisiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Coat Protein Complex I)
[Em] Mês de entrada:1612
[Cu] Atualização por classe:161230
[Lr] Data última revisão:
161230
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160427
[St] Status:MEDLINE
[do] DOI:10.1073/pnas.1604176113



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