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[PMID]:27776018
[Au] Autor:Vartanian A; Baryshnikova M; Burova O; Afanasyeva D; Misyurin V; Belyаvsky A; Shprakh Z
[Ad] Endereço:Department of Experimental Diagnosis and Therapy of Tumors, N.N. Blokhin Russian Cancer Research Center, Moscow, Russia.
[Ti] Título:Inhibitor of vasculogenic mimicry restores sensitivity of resistant melanoma cells to DNA-damaging agents.
[So] Source:Melanoma Res;27(1):8-16, 2017 Feb.
[Is] ISSN:1473-5636
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The increasing incidence of melanoma makes this cancer an important public health problem. Therapeutic resistance is still a major obstacle to the therapy of patients with metastatic melanomas. The aim of this study was to develop the melanoma cell line resistant to DNA-alkylating agents and to elucidate the mechanisms involved in acquired drug resistance. We established a unique melanoma subline Mel MeR resistant to DNA-alkylating drug aranoza by continuous stepwise selection of the Mel Me/WT cell line with increasing concentrations of this drug. Mel MeR cells were also cross-resistant to streptozotocin or cisplatin. Here, we show that aranoza-resistant melanoma cells modulate the ABC transporter activity, upregulate the expression of PRAME, adopt a vascular-related phenotype and engage in vasculogenic mimicry. LCS1269, a vasculogenic mimicry low-molecular-weight inhibitor, reverses the sensitivity of resistant melanoma cells to DNA-damaging agents. In this study, we provide experimental evidence that LCS1269 might be considered as a new potential anticancer agent capable of overcoming multidrug resistance for DNA-damaging agents in melanoma.
[Mh] Termos MeSH primário: Antineoplásicos Alquilantes/farmacologia
Carbazóis/farmacologia
Linhagem Celular Tumoral
Resistência a Medicamentos Antineoplásicos
Glicosídeos/farmacologia
Melanoma/tratamento farmacológico
Melanoma/metabolismo
Metilnitrosoureia/análogos & derivados
Neovascularização Patológica/prevenção & controle
[Mh] Termos MeSH secundário: Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo
Antígenos de Neoplasias/genética
Apoptose/efeitos dos fármacos
Antígeno CD24/metabolismo
Resistência a Medicamentos Antineoplásicos/genética
Endoglina/metabolismo
Corantes Fluorescentes/metabolismo
Expressão Gênica/efeitos dos fármacos
Seres Humanos
Receptores de Hialuronatos/metabolismo
Molécula 1 de Adesão Intercelular/metabolismo
Masculino
Melanoma/irrigação sanguínea
Melanoma/genética
Metilnitrosoureia/farmacologia
Meia-Idade
Proteínas de Neoplasias/genética
Células-Tronco Neoplásicas/metabolismo
Proteínas Nucleares/genética
Fenótipo
Fosfoproteínas Fosfatases/genética
Proteínas Proto-Oncogênicas c-kit/metabolismo
Rodamina 123/metabolismo
Tetraspanina 30/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (ABCB5 protein, human); 0 (ATP-Binding Cassette, Sub-Family B, Member 1); 0 (Antigens, Neoplasm); 0 (Antineoplastic Agents, Alkylating); 0 (CD24 Antigen); 0 (CD24 protein, human); 0 (CD44 protein, human); 0 (CD63 protein, human); 0 (Carbazoles); 0 (ENG protein, human); 0 (Endoglin); 0 (Fluorescent Dyes); 0 (GAGE1 protein, human); 0 (Glycosides); 0 (Hyaluronan Receptors); 0 (LCS1269); 0 (Neoplasm Proteins); 0 (Nuclear Proteins); 0 (PRAME protein, human); 0 (Tetraspanin 30); 0 (aranoza); 126547-89-5 (Intercellular Adhesion Molecule-1); 1N3CZ14C5O (Rhodamine 123); 684-93-5 (Methylnitrosourea); EC 2.7.10.1 (Proto-Oncogene Proteins c-kit); EC 3.1.3.16 (CTDSP1 protein, human); EC 3.1.3.16 (Phosphoprotein Phosphatases)
[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:161025
[St] Status:MEDLINE
[do] DOI:10.1097/CMR.0000000000000308


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[PMID]:29241732
[Au] Autor:Park YS; Choi SE; Koh HC
[Ad] Endereço:Department of Pharmacology, College of Medicine, Hanyang University, Seoul, Republic of Korea; Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul, Republic of Korea.
[Ti] Título:PGAM5 regulates PINK1/Parkin-mediated mitophagy via DRP1 in CCCP-induced mitochondrial dysfunction.
[So] Source:Toxicol Lett;284:120-128, 2018 Mar 01.
[Is] ISSN:1879-3169
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Mitochondrial dynamics and mitophagy are critical processes for regulating mitochondrial homeostasis. Phosphoglycerate mutase family member 5 (PGAM5) is a mitochondrial protein that plays crucial roles in apoptosis and necroptosis, but the roles of PGAM5 in mitochondrial dynamics and mitophagy remain unclear. In this study, we investigated the role of PGAM5 in carbonyl cyanide m-chlorophenylhydrazone (CCCP)-induced mitochondrial damage and the correlation between mitochondrial dynamics and mitophagy using SH-SY5Y cells. We found that CCCP decreased mitochondrial membrane potential, resulting in mitochondrial dysfunction. CCCP increased PGAM5, dynamin-related protein 1 (DRP1), and optic atrophy 1 (OPA1) expression of the mitochondrial fraction in a time-dependent manner. Knockdown of PGAM5 inhibited DRP1 translocation without a change in OPA1 expression in CCCP-treated cells. Furthermore, knockdown of PGAM5 and DRP1 significantly blocked the increase of PTEN-induced putative protein kinase 1 (PINK1) and Parkin expression in the mitochondrial fraction of CCCP-treated cells. Interestingly, CCCP did not alter PINK1/Parkin expression in the mitochondrial fraction of OPA1 knockdown cells. Inhibiting mitophagy by PGAM5 knockdown accelerated CCCP-induced apoptosis. CCCP treatment also results in PINK1 stabilization on the mitochondrial membrane, which subsequently increases Parkin recruitment from the cytosol to abnormal mitochondria. In addition, we found that CCCP increased the level of mitochondrial LC3II, indicating that Parkin recruitment of PINK1 is a result of mitophagy. We propose that activation of PGAM5 is associated with DRP1 recruitment and PINK1 stabilization, which contribute to the modulation of mitophagy in CCCP-treated cells with mitochondrial dysfunction. In conclusion, we demonstrated that PGAM5 regulates PINK1-Parkin-mediated mitophagy, which can exert a neuroprotective effect against CCCP-induced apoptosis.
[Mh] Termos MeSH primário: Carbonil Cianeto m-Clorofenil Hidrazona/toxicidade
GTP Fosfo-Hidrolases/metabolismo
Proteínas Associadas aos Microtúbulos/metabolismo
Degradação Mitocondrial/efeitos dos fármacos
Proteínas Mitocondriais/metabolismo
Fosfoproteínas Fosfatases/metabolismo
Proteínas Quinases/metabolismo
Ubiquitina-Proteína Ligases/metabolismo
[Mh] Termos MeSH secundário: Apoptose/efeitos dos fármacos
Linhagem Celular Tumoral
GTP Fosfo-Hidrolases/genética
Técnicas de Silenciamento de Genes
Seres Humanos
Potencial da Membrana Mitocondrial/efeitos dos fármacos
Proteínas Associadas aos Microtúbulos/genética
Mitocôndrias/efeitos dos fármacos
Mitocôndrias/metabolismo
Mitocôndrias/patologia
Proteínas Mitocondriais/genética
Fosfoproteínas Fosfatases/genética
Proteínas Quinases/genética
Ubiquitina-Proteína Ligases/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Microtubule-Associated Proteins); 0 (Mitochondrial Proteins); 555-60-2 (Carbonyl Cyanide m-Chlorophenyl Hydrazone); EC 2.3.2.27 (Ubiquitin-Protein Ligases); EC 2.3.2.27 (parkin protein); EC 2.7.- (Protein Kinases); EC 2.7.11.1 (PTEN-induced putative kinase); EC 3.1.3.16 (PGAM5 protein, human); EC 3.1.3.16 (Phosphoprotein Phosphatases); EC 3.6.1.- (GTP Phosphohydrolases); EC 3.6.5.5 (DNM1L protein, human)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180221
[Lr] Data última revisão:
180221
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171216
[St] Status:MEDLINE


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[PMID]:29338035
[Au] Autor:Bradai M; Mahjoubi H; Chini A; Chabouté ME; Hanin M; Ebel C
[Ad] Endereço:Laboratory of Biotechnology and Plant Improvement, Center of Biotechnology of Sfax, Sfax, Tunisia.
[Ti] Título:Genome wide identification of wheat and Brachypodium type one protein phosphatases and functional characterization of durum wheat TdPP1a.
[So] Source:PLoS One;13(1):e0191272, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Reversible phosphorylation is an essential mechanism regulating signal transduction during development and environmental stress responses. An important number of dephosphorylation events in the cell are catalyzed by type one protein phosphatases (PP1), which catalytic activity is driven by the binding of regulatory proteins that control their substrate specificity or subcellular localization. Plants harbor several PP1 isoforms accounting for large functional redundancies. While animal PP1s were reported to play relevant roles in controlling multiple cellular processes, plant orthologs remain poorly studied. To decipher the role of plant PP1s, we compared PP1 genes from three monocot species, Brachypodium, common wheat and rice at the genomic and transcriptomic levels. To gain more insight into the wheat PP1 proteins, we identified and characterized TdPP1a, the first wheat type one protein phosphatase from a Tunisian durum wheat variety Oum Rabiaa3. TdPP1a is highly conserved in sequence and structure when compared to mammalian, yeast and other plant PP1s. We demonstrate that TdPP1a is an active, metallo-dependent phosphatase in vitro and is able to interact with AtI2, a typical regulator of PP1 functions. Also, TdPP1a is capable to complement the heat stress sensitivity of the yeast mutant indicating that TdPP1a is functional also in vivo. Moreover, transient expression of TdPP1a::GFP in tobacco leaves revealed that it is ubiquitously distributed within the cell, with a strong accumulation in the nucleus. Finally, transcriptional analyses showed similar expression levels in roots and leaves of durum wheat seedlings. Interestingly, the expression in leaves is significantly induced following salinity stress, suggesting a potential role of TdPP1a in wheat salt stress response.
[Mh] Termos MeSH primário: Brachypodium/enzimologia
Brachypodium/genética
Fosfoproteínas Fosfatases/genética
Proteínas de Plantas/genética
Triticum/enzimologia
Triticum/genética
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Sequência Conservada
Evolução Molecular
Regulação Enzimológica da Expressão Gênica
Regulação da Expressão Gênica de Plantas
Isoenzimas/genética
Isoenzimas/metabolismo
Oryza/enzimologia
Oryza/genética
Fosfoproteínas Fosfatases/metabolismo
Filogenia
Proteínas de Plantas/metabolismo
Proteína Fosfatase 1/genética
Proteína Fosfatase 1/metabolismo
Homologia de Sequência de Aminoácidos
Especificidade da Espécie
Estresse Fisiológico
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Isoenzymes); 0 (Plant Proteins); EC 3.1.3.16 (Phosphoprotein Phosphatases); EC 3.1.3.16 (Protein Phosphatase 1)
[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:180117
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0191272


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[PMID]:29305265
[Au] Autor:Xu X; Okamoto K
[Ad] Endereço:Laboratory of Mitochondrial Dynamics, Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka 565-0871, Japan.
[Ti] Título:The Nem1-Spo7 protein phosphatase complex is required for efficient mitophagy in yeast.
[So] Source:Biochem Biophys Res Commun;496(1):51-57, 2018 01 29.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Mitochondria-targeted selective autophagy, termed mitophagy, is an evolutionarily conserved process that contributes to mitochondrial quantity and quality control. Mitophagy requires elaborate membrane biogenesis of autophagosomes surrounding mitochondria, although how this process is regulated remains obscure. We show here that mitophagy is strongly suppressed in yeast cells lacking Nem1 or Spo7, two proteins forming a heterodimeric protein phosphatase complex known to be important for proper shaping of the nucleus and endoplasmic reticulum (ER). Under the same conditions, selective degradation of the ER and peroxisomes was also suppressed strongly and to a lesser extent, respectively, whereas autophagy and the cytoplasm to vacuole targeting (Cvt) pathway were only slightly affected in those mutants. We also found that mitochondrial sequestration in the cytoplasm and their degradation in the vacuole, a lytic compartment in yeast, occurred poorly but did not completely arrest. Notably, deletion of the INO2 gene in the nem1-or spo7-null mutant partially rescued nuclear/ER membrane shaping and mitophagy. Together, our data suggest that Nem1-Sop7-mediated regulation of membrane biogenesis is needed to promote mitophagy in yeast.
[Mh] Termos MeSH primário: Proteínas de Membrana/metabolismo
Mitocôndrias/metabolismo
Degradação Mitocondrial/fisiologia
Proteínas Nucleares/metabolismo
Fosfoproteínas Fosfatases/metabolismo
Proteínas de Saccharomyces cerevisiae/metabolismo
Saccharomyces cerevisiae/metabolismo
[Mh] Termos MeSH secundário: Mitocôndrias/ultraestrutura
Saccharomyces cerevisiae/citologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Membrane Proteins); 0 (Nem1 protein, S cerevisiae); 0 (Nuclear Proteins); 0 (SPO7 protein, S cerevisiae); 0 (Saccharomyces cerevisiae Proteins); EC 3.1.3.16 (Phosphoprotein Phosphatases)
[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


  5 / 11184 MEDLINE  
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[PMID]:27777341
[Au] Autor:Hu CJ; Pan JB; Song G; Wen XT; Wu ZY; Chen S; Mo WX; Zhang FC; Qian J; Zhu H; Li YZ
[Ad] Endereço:From the ‡Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China100730.
[Ti] Título:Identification of Novel Biomarkers for Behcet Disease Diagnosis Using Human Proteome Microarray Approach.
[So] Source:Mol Cell Proteomics;16(2):147-156, 2017 Feb.
[Is] ISSN:1535-9484
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Behcet disease (BD) is a chronic systemic vasculitis and considered as an autoimmune disease. Although rare, BD can be fatal due to ruptured vascular aneurysms or severe neurological complications. To date, no known biomarker has been reported for this disease, making it difficult to diagnosis in the clinics. To undertake this challenge, we employed the HuProt arrays, each comprised of ∼20,000 unique human proteins, to identify BD-specific autoantibodies using a Two-Phase strategy established previously. In Phase I, we profiled the autoimmunity on the HuProt arrays with 75 serum samples collected from 40 BD patients, 15 diagnosed autoimmune patients who suffer from Takayasu arteritis (TA; n = 5)), ANCA associated vasculitis (AAV; n = 5), and Sjogren's syndrome (SS; n = 5), and 20 healthy subjects, and identified 20 candidate autoantigens that were significantly associated with BD. To validate these candidates, in Phase II we constructed a focused array with these 20 candidate BD-associated antigens, and use it to profile a much larger cohort, comprised of serum samples collected from 130 BD patients, 103 autoimmune patients (i.e. 40TA, 40 AAV and 23 SS), and 110 healthy controls. This allowed us to validate CTDP1 (RNA polymerase II subunit A C-terminal domain phosphatase)as a BD-specific autoantigen. The association of anti-CTDP1 with BD patients was further validated using the traditional Western blotting analysis. In conclusion, anti-CTDP1 antibody serves a novel autoantibody for Behcet disease and is expected to help more accurate clinical diagnosis.
[Mh] Termos MeSH primário: Síndrome de Behçet/diagnóstico
Fosfoproteínas Fosfatases/metabolismo
Análise Serial de Proteínas/métodos
Proteômica/métodos
[Mh] Termos MeSH secundário: Adulto
Autoanticorpos/imunologia
Autoantígenos/metabolismo
Síndrome de Behçet/imunologia
Biomarcadores/metabolismo
Feminino
Seres Humanos
Masculino
Meia-Idade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Autoantibodies); 0 (Autoantigens); 0 (Biomarkers); EC 3.1.3.16 (Phosphoprotein Phosphatases); EC 3.1.3.16 (carboxy-terminal domain phosphatase)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:180201
[Lr] Data última revisão:
180201
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161026
[St] Status:MEDLINE
[do] DOI:10.1074/mcp.M116.061002


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[PMID]:27771433
[Au] Autor:Wilson A; Yakovlev VA
[Ad] Endereço:Department of Radiation Oncology, Massey Cancer Center, Virginia Commonwealth University, 401 College Street, Richmond, VA 23298, United States.
[Ti] Título:Cells redox environment modulates BRCA1 expression and DNA homologous recombination repair.
[So] Source:Free Radic Biol Med;101:190-201, 2016 12.
[Is] ISSN:1873-4596
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Cancer development and progression have been linked to oxidative stress, a condition characterized by unbalanced increase in ROS and RNS production. The main endogenous initiators of the redox imbalance in cancer cells are defective mitochondria, elevated NOX activity, and uncoupled NOS3. Traditionally, most attention has been paid to direct oxidative damage to DNA by certain ROS. However, increase in oxidative DNA lesions does not always lead to malignancy. Hence, additional ROS-dependent, pro-carcinogenic mechanisms must be important. Our recent study demonstrated that Tyr nitration of PP2A stimulates its activity and leads to downregulation of BRCA1 expression. This provides a mechanism for chromosomal instability essential for tumor progression. In the present work, we demonstrated that inhibition of ROS production by generating mitochondrial-electron-transport-deficient cell lines (ρ cells) or by inhibition of NOX activity with a selective peptide inhibitor significantly reduced PP2A Tyr nitration and its activity in different cancer cell lines. As a result of the decreased PP2A activity, BRCA1 expression was restored along with a significantly enhanced level of DNA HRR. We used TCGA database to analyze the correlation between expressions of the NOX regulatory subunits, NOS isoforms, and BRCA1 in the 3 cancer research studies: breast invasive carcinoma, ovarian cystadenocarcinoma, and lung adenocarcinoma. TCGA database analysis demonstrated that the high expression levels of most of the NOX regulatory subunits responsible for stimulation of NOX1-NOX4 were associated with significant downregulation of BRCA1 expression.
[Mh] Termos MeSH primário: Regulação Neoplásica da Expressão Gênica
NADPH Oxidase 1/genética
Óxido Nítrico Sintase Tipo III/genética
Fosfoproteínas Fosfatases/genética
Reparo de DNA por Recombinação
Ubiquitina-Proteína Ligases/genética
[Mh] Termos MeSH secundário: Células A549
Adenocarcinoma/genética
Adenocarcinoma/metabolismo
Adenocarcinoma/patologia
Neoplasias da Mama/genética
Neoplasias da Mama/metabolismo
Neoplasias da Mama/patologia
Carcinoma Ductal de Mama/genética
Carcinoma Ductal de Mama/metabolismo
Carcinoma Ductal de Mama/patologia
Instabilidade Cromossômica
Cistadenocarcinoma Seroso/genética
Cistadenocarcinoma Seroso/metabolismo
Cistadenocarcinoma Seroso/patologia
Bases de Dados Genéticas
Transporte de Elétrons
Feminino
Seres Humanos
Isoenzimas/genética
Isoenzimas/metabolismo
Neoplasias Pulmonares/genética
Neoplasias Pulmonares/metabolismo
Neoplasias Pulmonares/patologia
Células MCF-7
Mitocôndrias/metabolismo
Mitocôndrias/patologia
NADPH Oxidase 1/metabolismo
Óxido Nítrico Sintase Tipo III/metabolismo
Neoplasias Ovarianas/genética
Neoplasias Ovarianas/metabolismo
Neoplasias Ovarianas/patologia
Oxirredução
Estresse Oxidativo
Fosfoproteínas Fosfatases/metabolismo
Espécies Reativas de Oxigênio/metabolismo
Transdução de Sinais
Ubiquitina-Proteína Ligases/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (Isoenzymes); 0 (Reactive Oxygen Species); EC 1.14.13.39 (NOS3 protein, human); EC 1.14.13.39 (Nitric Oxide Synthase Type III); EC 1.6.3.- (NADPH Oxidase 1); EC 1.6.3.- (NOX1 protein, human); EC 2.3.2.27 (BRAP protein, human); EC 2.3.2.27 (Ubiquitin-Protein Ligases); EC 3.1.3.16 (Phosphoprotein Phosphatases)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:180131
[Lr] Data última revisão:
180131
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161105
[St] Status:MEDLINE


  7 / 11184 MEDLINE  
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[PMID]:28448822
[Au] Autor:Ashton NW; Paquet N; Shirran SL; Bolderson E; Kariawasam R; Touma C; Fallahbaghery A; Gamsjaeger R; Cubeddu L; Botting C; Pollock PM; O'Byrne KJ; Richard DJ
[Ad] Endereço:School of Biomedical Research, Institute of Health and Biomedical Innovation at the Translational Research Institute, Queensland University of Technology, 37 Kent Street, Woolloongabba 4102, QLD, Australia. Electronic address: nicholas.ashton@nih.gov.
[Ti] Título:hSSB1 phosphorylation is dynamically regulated by DNA-PK and PPP-family protein phosphatases.
[So] Source:DNA Repair (Amst);54:30-39, 2017 06.
[Is] ISSN:1568-7856
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:The maintenance of genomic stability is essential for cellular viability and the prevention of diseases such as cancer. Human single-stranded DNA-binding protein 1 (hSSB1) is a protein with roles in the stabilisation and restart of stalled DNA replication forks, as well as in the repair of oxidative DNA lesions and double-strand DNA breaks. In the latter process, phosphorylation of threonine 117 by the ATM kinase is required for hSSB1 stability and efficient DNA repair. The regulation of hSSB1 in other DNA repair pathways has however remained unclear. Here we report that hSSB1 is also directly phosphorylated by DNA-PK at serine residue 134. While this modification is largely suppressed in undamaged cells by PPP-family protein phosphatases, S134 phosphorylation is enhanced following the disruption of replication forks and promotes cellular survival. Together, these data thereby represent a novel mechanism for hSSB1 regulation following the inhibition of replication.
[Mh] Termos MeSH primário: Reparo do DNA
Replicação do DNA
Proteína Quinase Ativada por DNA/metabolismo
Proteínas de Ligação a DNA/metabolismo
Proteínas Mitocondriais/metabolismo
Fosfoproteínas Fosfatases/metabolismo
[Mh] Termos MeSH secundário: Proteínas Mutadas de Ataxia Telangiectasia/metabolismo
DNA/metabolismo
Dano ao DNA
Proteínas de Ligação a DNA/química
Seres Humanos
Proteínas Mitocondriais/química
Fosforilação
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (DNA-Binding Proteins); 0 (Mitochondrial Proteins); 0 (SSBP1 protein, human); 9007-49-2 (DNA); EC 2.7.11.1 (ATM protein, human); EC 2.7.11.1 (Ataxia Telangiectasia Mutated Proteins); EC 2.7.11.1 (DNA-Activated Protein Kinase); EC 3.1.3.16 (Phosphoprotein Phosphatases)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:171204
[Lr] Data última revisão:
171204
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170428
[St] Status:MEDLINE


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[PMID]:29053956
[Au] Autor:Tan P; He L; Cui J; Qian C; Cao X; Lin M; Zhu Q; Li Y; Xing C; Yu X; Wang HY; Wang RF
[Ad] Endereço:Institute of Biosciences and Technology, College of Medicine, Texas A&M University, Houston, TX 77030, USA; Center for Inflammation and Epigenetics, Houston Methodist Research Institute, Houston, TX 77030, USA.
[Ti] Título:Assembly of the WHIP-TRIM14-PPP6C Mitochondrial Complex Promotes RIG-I-Mediated Antiviral Signaling.
[So] Source:Mol Cell;68(2):293-307.e5, 2017 Oct 19.
[Is] ISSN:1097-4164
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Mitochondrial antiviral signaling platform protein (MAVS) acts as a central hub for RIG-I receptor proximal signal propagation. However, key components in the assembly of the MAVS mitochondrial platform that promote RIG-I mitochondrial localization and optimal activation are still largely undefined. Employing pooled RNAi and yeast two-hybrid screenings, we report that the mitochondrial adaptor protein tripartite motif (TRIM)14 provides a docking platform for the assembly of the mitochondrial signaling complex required for maximal activation of RIG-I-mediated signaling, consisting of WHIP and protein phosphatase PPP6C. Following viral infection, the ubiquitin-binding domain in WHIP bridges RIG-I with MAVS by binding to polyUb chains of RIG-I at lysine 164. The ATPase domain in WHIP contributes to stabilization of the RIG-I-dsRNA interaction. Moreover, phosphatase PPP6C is responsible for RIG-I dephosphorylation. Together, our findings define the WHIP-TRIM14-PPP6C mitochondrial signalosome required for RIG-I-mediated innate antiviral immunity.
[Mh] Termos MeSH primário: Proteínas de Transporte/imunologia
Proteína DEAD-box 58/imunologia
Proteínas de Ligação a DNA/imunologia
Imunidade Inata
Mitocôndrias/imunologia
Proteínas Mitocondriais/imunologia
Complexos Multiproteicos/imunologia
Fosfoproteínas Fosfatases/imunologia
Transdução de Sinais/imunologia
[Mh] Termos MeSH secundário: ATPases Associadas a Diversas Atividades Celulares
Animais
Proteínas de Transporte/genética
Linhagem Celular Tumoral
Cercopithecus aethiops
Proteína DEAD-box 58/genética
Proteínas de Ligação a DNA/genética
Seres Humanos
Mitocôndrias/genética
Proteínas Mitocondriais/genética
Complexos Multiproteicos/genética
Fosfoproteínas Fosfatases/genética
Transdução de Sinais/genética
Células Vero
Viroses/genética
Viroses/imunologia
Vírus/genética
Vírus/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Carrier Proteins); 0 (DNA-Binding Proteins); 0 (Mitochondrial Proteins); 0 (Multiprotein Complexes); 0 (TRIM14 protein, human); EC 3.1.3.16 (Phosphoprotein Phosphatases); EC 3.1.3.16 (protein phosphatase 6); EC 3.6.1.- (DDX58 protein, human); EC 3.6.1.3 (WRNIP1 protein, human); EC 3.6.4.- (ATPases Associated with Diverse Cellular Activities); EC 3.6.4.13 (DEAD Box Protein 58)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171021
[St] Status:MEDLINE


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[PMID]:29045477
[Au] Autor:Saito S; Zhuang Y; Shan B; Danchuk S; Luo F; Korfei M; Guenther A; Lasky JA
[Ad] Endereço:Department of Medicine, Section of Pulmonary Diseases, Critical Care and Environmental Medicine, Tulane University Health Science Center, New Orleans, LA, United States of America.
[Ti] Título:Tubastatin ameliorates pulmonary fibrosis by targeting the TGFß-PI3K-Akt pathway.
[So] Source:PLoS One;12(10):e0186615, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive and fatal disease. Histone deacetylase 6 (HDAC6) alters function and fate of various proteins via deacetylation of lysine residues, and is implicated in TGF-ß1-induced EMT (epithelial-mesenchymal transition). However, the role of HDAC6 in pulmonary fibrosis is unknown. METHODS: HDAC6 expression in IPF and control lungs was assessed by quantitative real-time PCR (qRT-PCR) and immunoblots. Lung fibroblasts were treated with TGF-ß1 ± HDAC6 inhibitors (Tubacin, Tubastatin, ACY1215, or MC1568), and fibrotic markers such as type I collagen were assessed using qRT-PCR and immunoblots. Mice were treated with bleomycin (oropharyngeal aspiration; single dose) ± Tubastatin (intraperitoneally injection; daily for 21 days), and lung collagen expression was gauged using immunoblots and trichrome staining. In a separate experiment, HDAC6 wild-type (WT) and knockout (KO) mice were administered bleomycin, and lungs were evaluated in the same manner. RESULTS: HDAC6 expression was deregulated in IPF lungs. Among the HDAC6 inhibitors tested, only Tubastatin significantly repressed TGF-ß1-induced expression of type-1 collagen in lung fibroblasts, and this finding was coupled with decreased Akt phosphorylation and increased Akt-PHLPP (PH domain and Leucine rich repeat Protein Phosphatase) association. Tubastatin repressed TGF-ß1-induced S6K phosphorylation, HIF-1α expression, and VEGF expression. Tubastatin also repressed TGF-ß1-induced inhibition of LC3B-II (a marker of autophagosome formation). In bleomycin-treated mouse lungs, HDAC6 expression was increased, and Tubastatin repressed type-1 collagen expression. However, in HDAC6 KO mice, bleomycin-induced type-1 collagen expression was not repressed compared to WT mice. Knockdown of HDAC6, as well as HDAC10, another potential Tubastatin target, did not inhibit TGF-ß1-induced collagen expression in lung fibroblasts. CONCLUSIONS: HDAC6 expression is altered during lung fibrogenesis. Tubastatin represses TGF-ß1-induced collagen expression, by diminishing Akt phosphorylation and regulating downstream targets such as HIF-1α-VEGF axis and autophagy. Tubastatin-treated WT mice are protected against bleomycin-induced fibrosis, but HDAC6 KO mice are not. Our data suggest that Tubastatin ameliorates pulmonary fibrosis, by targeting the TGFß-PI3K-Akt pathway, likely via an HDAC6-independent mechanism.
[Mh] Termos MeSH primário: Ácidos Hidroxâmicos/uso terapêutico
Fibrose Pulmonar Idiopática/tratamento farmacológico
Fibrose Pulmonar Idiopática/metabolismo
Indóis/uso terapêutico
Fosfatidilinositol 3-Quinases/metabolismo
Proteínas Proto-Oncogênicas c-akt/metabolismo
Transdução de Sinais/efeitos dos fármacos
Fator de Crescimento Transformador beta/metabolismo
[Mh] Termos MeSH secundário: Idoso
Idoso de 80 Anos ou mais
Animais
Autofagossomos/efeitos dos fármacos
Autofagossomos/metabolismo
Autofagia/efeitos dos fármacos
Bleomicina
Colágeno Tipo I/metabolismo
Feminino
Fibroblastos/efeitos dos fármacos
Fibroblastos/metabolismo
Desacetilase 6 de Histona
Histona Desacetilases/genética
Histona Desacetilases/metabolismo
Seres Humanos
Ácidos Hidroxâmicos/farmacologia
Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo
Fibrose Pulmonar Idiopática/genética
Fibrose Pulmonar Idiopática/patologia
Indóis/farmacologia
Pulmão/metabolismo
Pulmão/patologia
Masculino
Alvo Mecanístico do Complexo 1 de Rapamicina
Camundongos Knockout
Meia-Idade
Complexos Multiproteicos/metabolismo
Proteínas Nucleares/metabolismo
Fosfoproteínas Fosfatases/metabolismo
Fosforilação/efeitos dos fármacos
RNA Mensageiro/genética
RNA Mensageiro/metabolismo
Proteínas Quinases S6 Ribossômicas/metabolismo
Serina-Treonina Quinases TOR/metabolismo
Fator de Crescimento Transformador beta/farmacologia
Tubulina (Proteína)/metabolismo
Fator A de Crescimento do Endotélio Vascular/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Collagen Type I); 0 (Hydroxamic Acids); 0 (Hypoxia-Inducible Factor 1, alpha Subunit); 0 (Indoles); 0 (Multiprotein Complexes); 0 (Nuclear Proteins); 0 (RNA, Messenger); 0 (Transforming Growth Factor beta); 0 (Tubulin); 0 (Vascular Endothelial Growth Factor A); 0 (tubastatin A); 11056-06-7 (Bleomycin); EC 2.7.1.- (Phosphatidylinositol 3-Kinases); EC 2.7.1.1 (TOR Serine-Threonine Kinases); EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 1); EC 2.7.11.1 (Proto-Oncogene Proteins c-akt); EC 2.7.11.1 (Ribosomal Protein S6 Kinases); EC 3.1.3.16 (PHLPP1 protein, human); EC 3.1.3.16 (Phosphoprotein Phosphatases); EC 3.5.1.98 (HDAC6 protein, human); EC 3.5.1.98 (Histone Deacetylase 6); EC 3.5.1.98 (Histone Deacetylases)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171019
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0186615


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[PMID]:28837603
[Au] Autor:Márkus B; Szabó K; Pfliegler WP; Petrényi K; Boros E; Pócsi I; Tozsér J; Csosz É; Dombrádi V
[Ad] Endereço:Proteomics Core Facility, Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
[Ti] Título:Proteomic analysis of protein phosphatase Z1 from Candida albicans.
[So] Source:PLoS One;12(8):e0183176, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Protein phosphatase Z is a "novel type" fungus specific serine/threonine protein phosphatase. Previously our research group identified the CaPPZ1 gene in the opportunistic pathogen Candida albicans and reported that the gene deletion had several important physiological consequences. In order to reveal the protein targets and the associated mechanisms behind the functions of the phosphatase a proteomic method was adopted for the comparison of the cappz1 deletion mutant and the genetically matching QMY23 control strain. Proteins extracted from the control and deletion mutant strains were separated by two-dimensional gel electrophoresis and the protein spots were stained with RuBPS and Pro-Q Diamond in order to visualize the total proteome and the phosphoproteome, respectively. The alterations in spot intensities were determined by densitometry and were analysed with the Delta2D (Decodon) software. Spots showing significantly different intensities between the mutant and control strains were excised from the gels and were digested with trypsin. The resulting peptides were identified by LC-MS/MS mass spectrometry. As many as 15 protein spots were found that exhibited significant changes in their intensity upon the deletion of the phosphatase and 20 phosphoproteins were identified in which the level of phosphorylation was modified significantly in the mutant. In agreement with previous findings we found that the affected proteins function in protein synthesis, oxidative stress response, regulation of morphology and metabolism. Among these proteins we identified two potential CaPpz1 substrates (Eft2 and Rpp0) that may regulate the elongation step of translation. RT-qPCR experiments revealed that the expression of the genes coding for the affected proteins was not altered significantly. Thus, the absence of CaPpz1 exerted its effects via protein synthesis/degradation and phosphorylation/dephosphorylation. In addition, our proteomics data strongly suggested a role for CaPpz1 in biofilm formation, was confirmed experimentally. Thus our unbiased proteomic approach lead to the discovery of a novel function for this phosphatase in C. albicans.
[Mh] Termos MeSH primário: Candida albicans/metabolismo
Proteínas Fúngicas/metabolismo
Fosfoproteínas Fosfatases/metabolismo
Proteômica
[Mh] Termos MeSH secundário: Biofilmes
Eletroforese em Gel Bidimensional
Fosforilação
Espectrometria de Massas em Tandem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Fungal Proteins); EC 3.1.3.16 (Phosphoprotein Phosphatases)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171023
[Lr] Data última revisão:
171023
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170825
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0183176



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