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Pesquisa : D12.776.947.249 [Categoria DeCS]
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[PMID]:29351565
[Au] Autor:Peek J; Harvey C; Gray D; Rosenberg D; Kolla L; Levy-Myers R; Yin R; McMurry JL; Kerscher O
[Ad] Endereço:Biology Department, The College of William & Mary, Williamsburg, Virginia, United States of America.
[Ti] Título:SUMO targeting of a stress-tolerant Ulp1 SUMO protease.
[So] Source:PLoS One;13(1):e0191391, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:SUMO proteases of the SENP/Ulp family are master regulators of both sumoylation and desumoylation and regulate SUMO homeostasis in eukaryotic cells. SUMO conjugates rapidly increase in response to cellular stress, including nutrient starvation, hypoxia, osmotic stress, DNA damage, heat shock, and other proteotoxic stressors. Nevertheless, little is known about the regulation and targeting of SUMO proteases during stress. To this end we have undertaken a detailed comparison of the SUMO-binding activity of the budding yeast protein Ulp1 (ScUlp1) and its ortholog in the thermotolerant yeast Kluyveromyces marxianus, KmUlp1. We find that the catalytic UD domains of both ScUlp1 and KmUlp1 show a high degree of sequence conservation, complement a ulp1Δ mutant in vivo, and process a SUMO precursor in vitro. Next, to compare the SUMO-trapping features of both SUMO proteases we produced catalytically inactive recombinant fragments of the UD domains of ScUlp1 and KmUlp1, termed ScUTAG and KmUTAG respectively. Both ScUTAG and KmUTAG were able to efficiently bind a variety of purified SUMO isoforms and bound immobilized SUMO1 with nanomolar affinity. However, KmUTAG showed a greatly enhanced ability to bind SUMO and SUMO-modified proteins in the presence of oxidative, temperature and other stressors that induce protein misfolding. We also investigated whether a SUMO-interacting motif (SIM) in the UD domain of KmULP1 that is not conserved in ScUlp1 may contribute to the SUMO-binding properties of KmUTAG. In summary, our data reveal important details about how SUMO proteases target and bind their sumoylated substrates, especially under stress conditions. We also show that the robust pan-SUMO binding features of KmUTAG can be exploited to detect and study SUMO-modified proteins in cell culture systems.
[Mh] Termos MeSH primário: Cisteína Endopeptidases/metabolismo
Proteínas Fúngicas/metabolismo
Proteínas de Saccharomyces cerevisiae/metabolismo
Proteínas Modificadoras Pequenas Relacionadas à Ubiquitina/metabolismo
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Domínio Catalítico/genética
Sequência Conservada
Cisteína Endopeptidases/química
Cisteína Endopeptidases/genética
Proteínas Fúngicas/química
Proteínas Fúngicas/genética
Teste de Complementação Genética
Kluyveromyces/genética
Kluyveromyces/metabolismo
Modelos Moleculares
Proteínas Mutantes/química
Proteínas Mutantes/genética
Proteínas Mutantes/metabolismo
Ligação Proteica
Processamento de Proteína Pós-Traducional
Saccharomyces cerevisiae/genética
Saccharomyces cerevisiae/metabolismo
Proteínas de Saccharomyces cerevisiae/química
Proteínas de Saccharomyces cerevisiae/genética
Homologia de Sequência de Aminoácidos
Estresse Fisiológico
Sumoilação
Temperatura Ambiente
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Fungal Proteins); 0 (Mutant Proteins); 0 (Saccharomyces cerevisiae Proteins); 0 (Small Ubiquitin-Related Modifier Proteins); EC 3.4.22.- (Cysteine Endopeptidases); EC 3.4.22.- (Ulp1 protease)
[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:180120
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0191391


  2 / 1538 MEDLINE  
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[PMID]:29246538
[Au] Autor:Ranieri M; Vivo M; De Simone M; Guerrini L; Pollice A; La Mantia G; Calabrò V
[Ad] Endereço:Department of Developmental and Molecular Biology Albert Einstein College of Medicine, United States.
[Ti] Título:Sumoylation and ubiquitylation crosstalk in the control of ΔNp63α protein stability.
[So] Source:Gene;645:34-40, 2018 Mar 01.
[Is] ISSN:1879-0038
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:ΔNp63α is finely and strictly regulated during embryogenesis and differentiation. ΔNp63α is the only p63 isoform degraded by the proteasome after Ubiquitin and SUMO (Small Ubiquitin-like MOdifier) conjugation. Here, we show that p63 ubiquitylation per se is not the signal triggering p63 proteasomal degradation. Taking advantage of natural ΔNp63α mutants isolated by patients with Split Hand and Foot Malformation IV syndrome, we found that SUMO and Ub modifications are not redundant and both are required to guarantee efficient ΔNp63α degradation. Here, we present evidence that sumoylation and ubiquitylation of ΔNp63α are strongly intertwined, and none of the two can efficiently occur if the other is impaired.
[Mh] Termos MeSH primário: Fatores de Transcrição/química
Fatores de Transcrição/metabolismo
Proteínas Supressoras de Tumor/química
Proteínas Supressoras de Tumor/metabolismo
[Mh] Termos MeSH secundário: Linhagem Celular
Células HEK293
Seres Humanos
Deformidades Congênitas dos Membros/genética
Peso Molecular
Mutação
Complexo de Endopeptidases do Proteassoma/química
Complexo de Endopeptidases do Proteassoma/metabolismo
Estabilidade Proteica
Proteínas Modificadoras Pequenas Relacionadas à Ubiquitina/metabolismo
Sumoilação
Fatores de Transcrição/genética
Proteínas Supressoras de Tumor/genética
Ubiquitina/metabolismo
Ubiquitinação
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Small Ubiquitin-Related Modifier Proteins); 0 (TP63 protein, human); 0 (Transcription Factors); 0 (Tumor Suppressor Proteins); 0 (Ubiquitin); EC 3.4.25.1 (Proteasome Endopeptidase Complex)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180129
[Lr] Data última revisão:
180129
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171217
[St] Status:MEDLINE


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[PMID]:28465351
[Au] Autor:Morimoto A; Kannari M; Tsuchida Y; Sasaki S; Saito C; Matsuta T; Maeda T; Akiyama M; Nakamura T; Sakaguchi M; Nameki N; Gonzalez FJ; Inoue Y
[Ad] Endereço:From the Laboratory of Molecular Life Science, Division of Molecular Science, Faculty of Science and Technology, Gunma University, Kiryu, Gunma 376-8515, Japan.
[Ti] Título:An HNF4α-microRNA-194/192 signaling axis maintains hepatic cell function.
[So] Source:J Biol Chem;292(25):10574-10585, 2017 06 23.
[Is] ISSN:1083-351X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Hepatocyte nuclear factor 4α (HNF4α) controls the expression of liver-specific protein-coding genes. However, some microRNAs are also modulated by HNF4α, and it is not known whether they are direct targets of HNF4α and whether they influence hepatic function. In this study, we found that HNF4α regulates microRNAs, indicated by marked down-regulation of miR-194 and miR-192 (miR-194/192) in liver-specific -null ( ) mice. Transactivation of the shared miR-194/192 promoter was dependent on HNF4α expression, indicating that miR-194/192 is a target gene of HNF4α. Screening of potential mRNAs targeted by miR-194/192 revealed that expression of genes involved in glucose metabolism (glycogenin 1 ( )), cell adhesion and migration (activated leukocyte cell adhesion molecule ( )), tumorigenesis and tumor progression ( and epiregulin ( )), protein SUMOylation ( ), epigenetic regulation ( and Cullin 4B ( )), and the epithelial-mesenchymal transition (moesin ( )) was up-regulated in mice. Moreover, we also found that miR-194/192 binds the 3'-UTR of these mRNAs. siRNA knockdown of HNF4α suppressed miR-194/192 expression in human hepatocellular carcinoma (HCC) cells and resulted in up-regulation of their mRNA targets. Inhibition and overexpression experiments with miR-194/192 revealed that , , , , and are miR-194 targets, whereas , , and are miR-192 targets. These findings reveal a novel HNF4α network controlled by miR-194/192 that may play a critical role in maintaining the hepatocyte-differentiated state by inhibiting expression of genes involved in dedifferentiation and tumorigenesis. These insights may contribute to the development of diagnostic markers for early HCC detection, and targeting of the miR-194/192 pathway could be useful for managing HCC.
[Mh] Termos MeSH primário: Regulação da Expressão Gênica/fisiologia
Fator 4 Nuclear de Hepatócito/metabolismo
Hepatócitos/metabolismo
MicroRNAs/metabolismo
Transdução de Sinais/fisiologia
[Mh] Termos MeSH secundário: Regiões 3' não Traduzidas/fisiologia
Molécula de Adesão de Leucócito Ativado/biossíntese
Molécula de Adesão de Leucócito Ativado/genética
Animais
Transformação Celular Neoplásica/genética
Transformação Celular Neoplásica/metabolismo
Epirregulina/biossíntese
Epirregulina/genética
Glucosiltransferases/biossíntese
Glucosiltransferases/genética
Glicoproteínas/biossíntese
Glicoproteínas/genética
Fator 4 Nuclear de Hepatócito/genética
Neoplasias Hepáticas/genética
Neoplasias Hepáticas/metabolismo
Camundongos
Camundongos Mutantes
MicroRNAs/genética
Proteínas dos Microfilamentos/biossíntese
Proteínas dos Microfilamentos/genética
Proteínas Modificadoras Pequenas Relacionadas à Ubiquitina/biossíntese
Proteínas Modificadoras Pequenas Relacionadas à Ubiquitina/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (3' Untranslated Regions); 0 (Activated-Leukocyte Cell Adhesion Molecule); 0 (Epiregulin); 0 (Ereg protein, mouse); 0 (Glycoproteins); 0 (Hepatocyte Nuclear Factor 4); 0 (Hnf4a protein, mouse); 0 (MIRN194 microRNA, mouse); 0 (MicroRNAs); 0 (Microfilament Proteins); 0 (Mirn192 microRNA, mouse); 0 (SUMO2 protein, mouse); 0 (Small Ubiquitin-Related Modifier Proteins); 0 (glycogenin); 144131-77-1 (moesin); EC 2.4.1.- (Glucosyltransferases)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:171229
[Lr] Data última revisão:
171229
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170504
[St] Status:MEDLINE
[do] DOI:10.1074/jbc.M117.785592


  4 / 1538 MEDLINE  
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[PMID]:28455449
[Au] Autor:Kaur K; Park H; Pandey N; Azuma Y; De Guzman RN
[Ad] Endereço:From the Department of Molecular Biosciences, University of Kansas, Lawrence, Kansas 66045.
[Ti] Título:Identification of a new small ubiquitin-like modifier (SUMO)-interacting motif in the E3 ligase PIASy.
[So] Source:J Biol Chem;292(24):10230-10238, 2017 06 16.
[Is] ISSN:1083-351X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Small ubiquitin-like modifier (SUMO) conjugation is a reversible post-translational modification process implicated in the regulation of gene transcription, DNA repair, and cell cycle. SUMOylation depends on the sequential activities of E1 activating, E2 conjugating, and E3 ligating enzymes. SUMO E3 ligases enhance transfer of SUMO from the charged E2 enzyme to the substrate. We have previously identified PIASy, a member of the Siz/protein inhibitor of activated STAT (PIAS) RING family of SUMO E3 ligases, as essential for mitotic chromosomal SUMOylation in frog egg extracts and demonstrated that it can mediate effective SUMOylation. To address how PIASy catalyzes SUMOylation, we examined various truncations of PIASy for their ability to mediate SUMOylation. Using NMR chemical shift mapping and mutagenesis, we identified a new SUMO-interacting motif (SIM) in PIASy. The new SIM and the currently known SIM are both located at the C terminus of PIASy, and both are required for the full ligase activity of PIASy. Our results provide novel insights into the mechanism of PIASy-mediated SUMOylation. PIASy adds to the growing list of SUMO E3 ligases containing multiple SIMs that play important roles in the E3 ligase activity.
[Mh] Termos MeSH primário: Modelos Moleculares
Proteínas Inibidoras de STAT Ativados/metabolismo
Proteínas Repressoras/metabolismo
Proteínas Modificadoras Pequenas Relacionadas à Ubiquitina/metabolismo
Sumoilação
Ubiquitinas/metabolismo
Proteínas de Xenopus/metabolismo
[Mh] Termos MeSH secundário: Motivos de Aminoácidos
Animais
Deleção de Genes
Seres Humanos
Interações Hidrofóbicas e Hidrofílicas
Ligantes
Mutagênese Sítio-Dirigida
Mutação
Isótopos de Nitrogênio
Fragmentos de Peptídeos/química
Fragmentos de Peptídeos/genética
Fragmentos de Peptídeos/metabolismo
Proteínas Inibidoras de STAT Ativados/química
Proteínas Inibidoras de STAT Ativados/genética
Domínios e Motivos de Interação entre Proteínas
Proteínas Recombinantes de Fusão/química
Proteínas Recombinantes de Fusão/metabolismo
Proteínas Recombinantes/química
Proteínas Recombinantes/metabolismo
Proteínas Repressoras/química
Proteínas Repressoras/genética
Proteínas Modificadoras Pequenas Relacionadas à Ubiquitina/química
Proteínas Modificadoras Pequenas Relacionadas à Ubiquitina/genética
Ubiquitinas/química
Ubiquitinas/genética
Proteínas de Xenopus/química
Proteínas de Xenopus/genética
Xenopus laevis
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (Ligands); 0 (Nitrogen Isotopes); 0 (PIASy protein, Xenopus); 0 (Peptide Fragments); 0 (Protein Inhibitors of Activated STAT); 0 (Recombinant Fusion Proteins); 0 (Recombinant Proteins); 0 (Repressor Proteins); 0 (SUMO2 protein, human); 0 (SUMO3 protein, human); 0 (Small Ubiquitin-Related Modifier Proteins); 0 (Ubiquitins); 0 (Xenopus Proteins)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:171228
[Lr] Data última revisão:
171228
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170430
[St] Status:MEDLINE
[do] DOI:10.1074/jbc.M117.789982


  5 / 1538 MEDLINE  
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[PMID]:28740167
[Au] Autor:Soria-Bretones I; Cepeda-García C; Checa-Rodriguez C; Heyer V; Reina-San-Martin B; Soutoglou E; Huertas P
[Ad] Endereço:Departamento de Genética, Universidad de Sevilla, Sevilla, 41080, Spain.
[Ti] Título:DNA end resection requires constitutive sumoylation of CtIP by CBX4.
[So] Source:Nat Commun;8(1):113, 2017 07 24.
[Is] ISSN:2041-1723
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:DNA breaks are complex DNA lesions that can be repaired by two alternative mechanisms: non-homologous end-joining and homologous recombination. The decision between them depends on the activation of the DNA resection machinery, which blocks non-homologous end-joining and stimulates recombination. On the other hand, post-translational modifications play a critical role in DNA repair. We have found that the SUMO E3 ligase CBX4 controls resection through the key factor CtIP. Indeed, CBX4 depletion impairs CtIP constitutive sumoylation and DNA end processing. Importantly, mutating lysine 896 in CtIP recapitulates the CBX4-depletion phenotype, blocks homologous recombination and increases genomic instability. Artificial fusion of CtIP and SUMO suppresses the effects of both the non-sumoylatable CtIP mutant and CBX4 depletion. Mechanistically, CtIP sumoylation is essential for its recruitment to damaged DNA. In summary, sumoylation of CtIP at lysine 896 defines a subpopulation of the protein that is involved in DNA resection and recombination.The choice between non-homologous end-joining and homologous recombination to repair a DNA double-strand break depends on activation of the end resection machinery. Here the authors show that SUMO E3 ligase CBX4 sumoylates subpopulation of CtIP to regulate recruitment to breaks and resection.
[Mh] Termos MeSH primário: Proteínas de Transporte/metabolismo
Quebras de DNA de Cadeia Dupla
Reparo do DNA por Junção de Extremidades
Ligases/metabolismo
Proteínas Nucleares/metabolismo
Proteínas do Grupo Polycomb/metabolismo
[Mh] Termos MeSH secundário: Western Blotting
Proteínas de Transporte/genética
Linhagem Celular Tumoral
DNA/genética
DNA/metabolismo
Células HEK293
Recombinação Homóloga
Seres Humanos
Ligases/genética
Microscopia Confocal
Proteínas Nucleares/genética
Proteínas do Grupo Polycomb/genética
Interferência de RNA
Proteína SUMO-1/genética
Proteína SUMO-1/metabolismo
Proteínas Modificadoras Pequenas Relacionadas à Ubiquitina/genética
Proteínas Modificadoras Pequenas Relacionadas à Ubiquitina/metabolismo
Sumoilação
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Carrier Proteins); 0 (Nuclear Proteins); 0 (Polycomb-Group Proteins); 0 (RBBP8 protein, human); 0 (SUMO-1 Protein); 0 (SUMO1 protein, human); 0 (SUMO2 protein, human); 0 (Small Ubiquitin-Related Modifier Proteins); 9007-49-2 (DNA); EC 6.- (Ligases); EC 6.3.2.- (CBX4 protein, human)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171128
[Lr] Data última revisão:
171128
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170726
[St] Status:MEDLINE
[do] DOI:10.1038/s41467-017-00183-6


  6 / 1538 MEDLINE  
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[PMID]:28892090
[Au] Autor:He X; Riceberg J; Soucy T; Koenig E; Minissale J; Gallery M; Bernard H; Yang X; Liao H; Rabino C; Shah P; Xega K; Yan ZH; Sintchak M; Bradley J; Xu H; Duffey M; England D; Mizutani H; Hu Z; Guo J; Chau R; Dick LR; Brownell JE; Newcomb J; Langston S; Lightcap ES; Bence N; Pulukuri SM
[Ad] Endereço:Oncology Drug Discovery Unit, Takeda Pharmaceuticals International Co., Cambridge, Massachusetts, USA.
[Ti] Título:Probing the roles of SUMOylation in cancer cell biology by using a selective SAE inhibitor.
[So] Source:Nat Chem Biol;13(11):1164-1171, 2017 Nov.
[Is] ISSN:1552-4469
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Small ubiquitin-like modifier (SUMO) family proteins regulate target-protein functions by post-translational modification. However, a potent and selective inhibitor targeting the SUMO pathway has been lacking. Here we describe ML-792, a mechanism-based SUMO-activating enzyme (SAE) inhibitor with nanomolar potency in cellular assays. ML-792 selectively blocks SAE enzyme activity and total SUMOylation, thus decreasing cancer cell proliferation. Moreover, we found that induction of the MYC oncogene increased the ML-792-mediated viability effect in cancer cells, thus indicating a potential application of SAE inhibitors in treating MYC-amplified tumors. Using ML-792, we further explored the critical roles of SUMOylation in mitotic progression and chromosome segregation. Furthermore, expression of an SAE catalytic-subunit (UBA2) S95N M97T mutant rescued SUMOylation loss and the mitotic defect induced by ML-792, thus confirming the selectivity of ML-792. As a potent and selective SAE inhibitor, ML-792 provides rapid loss of endogenously SUMOylated proteins, thereby facilitating novel insights into SUMO biology.
[Mh] Termos MeSH primário: Inibidores Enzimáticos/farmacologia
Neoplasias/tratamento farmacológico
Neoplasias/metabolismo
Proteínas Modificadoras Pequenas Relacionadas à Ubiquitina/antagonistas & inibidores
Sumoilação
[Mh] Termos MeSH secundário: Proliferação Celular/efeitos dos fármacos
Segregação de Cromossomos/efeitos dos fármacos
Dano ao DNA/efeitos dos fármacos
Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos
Genes myc
Seres Humanos
Mitose/efeitos dos fármacos
Neoplasias/genética
Neoplasias/patologia
Processamento de Proteína Pós-Traducional
Células Tumorais Cultivadas
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Enzyme Inhibitors); 0 (Small Ubiquitin-Related Modifier Proteins)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171026
[Lr] Data última revisão:
171026
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170912
[St] Status:MEDLINE
[do] DOI:10.1038/nchembio.2463


  7 / 1538 MEDLINE  
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[PMID]:28784659
[Au] Autor:Wiechmann S; Gärtner A; Kniss A; Stengl A; Behrends C; Rogov VV; Rodriguez MS; Dötsch V; Müller S; Ernst A
[Ad] Endereço:From the Institute of Biochemistry II, Goethe University School of Medicine, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany.
[Ti] Título:Site-specific inhibition of the small ubiquitin-like modifier (SUMO)-conjugating enzyme Ubc9 selectively impairs SUMO chain formation.
[So] Source:J Biol Chem;292(37):15340-15351, 2017 Sep 15.
[Is] ISSN:1083-351X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Posttranslational modifications by small ubiquitin-like modifiers (SUMOs) regulate many cellular processes, including genome integrity, gene expression, and ribosome biogenesis. The E2-conjugating enzyme Ubc9 catalyzes the conjugation of SUMOs to ϵ-amino groups of lysine residues in target proteins. Attachment of SUMO moieties to internal lysines in Ubc9 itself can further lead to the formation of polymeric SUMO chains. Mono- and poly-SUMOylations of target proteins provide docking sites for distinct adapter and effector proteins important for regulating discrete SUMO-regulated pathways. However, molecular tools to dissect pathways depending on either mono- or poly-SUMOylation are largely missing. Using a protein-engineering approach, we generated high-affinity SUMO2 variants by phage display that bind the back side binding site of Ubc9 and function as SUMO-based Ubc9 inhibitors (SUBINs). Importantly, we found that distinct SUBINs primarily inhibit poly-SUMO chain formation, whereas mono-SUMOylation was not impaired. Proof-of-principle experiments demonstrated that in a cellular context, SUBINs largely prevent heat shock-triggered poly-SUMOylation. Moreover, SUBINs abrogated arsenic-induced degradation of promyelocytic leukemia protein. We propose that the availability of the new chain-selective SUMO inhibitors reported here will enable a thorough investigation of poly-SUMO-mediated cellular processes, such as DNA damage responses and cell cycle progression.
[Mh] Termos MeSH primário: Modelos Moleculares
Proteína da Leucemia Promielocítica/metabolismo
Proteínas Modificadoras Pequenas Relacionadas à Ubiquitina/metabolismo
Sumoilação
Enzimas de Conjugação de Ubiquitina/metabolismo
[Mh] Termos MeSH secundário: Substituição de Aminoácidos
Arsênico/toxicidade
Sítios de Ligação
Ligação Competitiva
Deleção de Genes
Biblioteca Gênica
Células HEK293
Células HeLa
Temperatura Alta
Seres Humanos
Ligantes
Fragmentos de Peptídeos/química
Fragmentos de Peptídeos/genética
Fragmentos de Peptídeos/metabolismo
Mutação Puntual
Proteína da Leucemia Promielocítica/antagonistas & inibidores
Proteína da Leucemia Promielocítica/química
Proteína da Leucemia Promielocítica/genética
Domínios e Motivos de Interação entre Proteínas
Interferência de RNA
Proteínas Recombinantes de Fusão/química
Proteínas Recombinantes de Fusão/metabolismo
Proteínas Recombinantes/química
Proteínas Recombinantes/metabolismo
Proteínas Modificadoras Pequenas Relacionadas à Ubiquitina/química
Proteínas Modificadoras Pequenas Relacionadas à Ubiquitina/genética
Sumoilação/efeitos dos fármacos
Enzimas de Conjugação de Ubiquitina/antagonistas & inibidores
Enzimas de Conjugação de Ubiquitina/química
Enzimas de Conjugação de Ubiquitina/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Ligands); 0 (Peptide Fragments); 0 (Promyelocytic Leukemia Protein); 0 (Recombinant Fusion Proteins); 0 (Recombinant Proteins); 0 (SUMO2 protein, human); 0 (Small Ubiquitin-Related Modifier Proteins); 143220-95-5 (PML protein, human); EC 2.3.2.23 (Ubiquitin-Conjugating Enzymes); EC 6.3.2.- (ubiquitin-conjugating enzyme UBC9); N712M78A8G (Arsenic)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170927
[Lr] Data última revisão:
170927
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170809
[St] Status:MEDLINE
[do] DOI:10.1074/jbc.M117.794255


  8 / 1538 MEDLINE  
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[PMID]:28689037
[Au] Autor:Zhang T; Liu Y; Hu Y; Zhang X; Zhong L; Fan J; Peng Z
[Ad] Endereço:Department of Hepatobiliary Pancreatic Surgery, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
[Ti] Título:Association of donor and recipient SUMO4 rs237025 genetic variant with new-onset diabetes mellitus after liver transplantation in a Chinese population.
[So] Source:Gene;627:428-433, 2017 Sep 05.
[Is] ISSN:1879-0038
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:BACKGROUNDS & AIMS: New-onset diabetes mellitus (NODM) is a common complication after liver transplantation (LT). The small ubiquitin-like modifier 4 (SUMO4) rs237025 polymorphism has been reported to be associated with type 2 diabetes mellitus (T2DM). In this study, we aimed to evaluate the association of donor and recipient SUMO4 rs237025 polymorphisms with NODM and the long-term consequences of NODM after LT. METHODS: A total of 126 liver transplant patients were enrolled in the study. One single nucleotide polymorphism, SUMO4 rs237025, was genotyped in both donors and recipients. RESULTS: Both donor and recipient SUMO4 rs237025 polymorphisms were found to be significantly associated with NODM after LT. In multivariate analysis, recipient age>50 years, tacrolimus trough concentrations>10ng/mL at 1month after LT, donor and recipient rs237025 genetic variant, and the combined donor and recipient rs237025 genetic variant were independent predictive factors of NODM. Area under the receiver operating characteristic curve (AUROC) analysis indicated the higher predictive ability of the model containing combined donor and recipient rs237025 polymorphisms than the clinical model (p=0.046). Furthermore, Kaplan-Meier survival analysis demonstrated that NODM was related to significantly poorer patient survival in comparison with non-NODM patients (p=0.041). CONCLUSIONS: Both donor and recipient SUMO4 rs237025 polymorphisms contribute to the development of NODM after LT and NODM is a frequent complication that negatively affects patient survival.
[Mh] Termos MeSH primário: Diabetes Mellitus/genética
Transplante de Fígado/efeitos adversos
Polimorfismo de Nucleotídeo Único
Complicações Pós-Operatórias/genética
Proteínas Modificadoras Pequenas Relacionadas à Ubiquitina/genética
Doadores de Tecidos
Transplantados
[Mh] Termos MeSH secundário: Adulto
Idoso
China
Diabetes Mellitus/etiologia
Feminino
Seres Humanos
Masculino
Meia-Idade
Complicações Pós-Operatórias/etiologia
Análise de Sobrevida
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (SUMO4 protein, human); 0 (Small Ubiquitin-Related Modifier Proteins)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170920
[Lr] Data última revisão:
170920
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170710
[St] Status:MEDLINE


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[PMID]:28545138
[Au] Autor:Baczyk D; Audette MC; Drewlo S; Levytska K; Kingdom JC
[Ad] Endereço:Program in Development and Fetal Health, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Canada.
[Ti] Título:SUMO-4: A novel functional candidate in the human placental protein SUMOylation machinery.
[So] Source:PLoS One;12(5):e0178056, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Small ubiquitin-like modifiers (SUMOs) conjugate to proteins post-translationally, thereby affecting target localization, activity and stability. Functional SUMO family members identified in the human placenta include SUMO-1 to SUMO-3, which are elevated in pre-eclampsia. Whether the fourth isoform, SUMO-4, plays a role in placental development and function remains unknown. OBJECTIVES: We tested the hypothesis that SUMO-4 is expressed in the human placenta and demonstrates altered SUMOylation in pre-eclamptic pregnancies. METHODS: SUMO-4 mRNA (qRT-PCR) and protein (Western blot and immunohistochemistry) were measured in Jar cells, BeWo cells, first trimester placental villous explants and placental tissues across normal gestation and in pre-eclampsia. SUMO-4 expression in response to oxidative stress (H2O2: 0, 0.1, 1 and 5mM), as well as, hypoxia-reperfusion (O2: 1%, 8% and 20%) was measured. Lastly, SUMO-4 binding (covalently vs. non-covalently) to target proteins was investigated. RESULTS: SUMO-4 mRNA and protein were unchanged across gestation. SUMO-4 was present in the villous trophoblast layer throughout gestation. SUMO-4 mRNA expression and protein levels were increased ~2.2-fold and ~1.8-fold in pre-eclamptic placentas compared to age-matched controls, respectively (p<0.01). SUMO-4 mRNA and protein expression increased in Jars, BeWos and first trimester placental explants with 5mM H2O2 treatment, as well as with exposure to hypoxia-reperfusion. SUMO-1 to SUMO-3 did not show consistent trends across models. SUMO-4 hyper-SUMOylation was predominantly covalent in nature. CONCLUSIONS: SUMO-4 is expressed in normal placental development. SUMO-4 expression was increased in pre-eclamptic placentas and in models of oxidative stress and hypoxic injury. These data suggests that SUMO-4 hyper-SUMOylation may be a potential post-translational mechanism in the stressed pre-eclamptic placenta.
[Mh] Termos MeSH primário: Placenta/metabolismo
Pré-Eclâmpsia/metabolismo
Proteínas da Gravidez/metabolismo
Proteínas Modificadoras Pequenas Relacionadas à Ubiquitina/genética
Proteínas Modificadoras Pequenas Relacionadas à Ubiquitina/metabolismo
[Mh] Termos MeSH secundário: Hipóxia Celular
Células Cultivadas
Feminino
Seres Humanos
Estresse Oxidativo
Placentação
Pré-Eclâmpsia/genética
Gravidez
Sumoilação
Trofoblastos/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Pregnancy Proteins); 0 (SUMO4 protein, human); 0 (Small Ubiquitin-Related Modifier Proteins)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170919
[Lr] Data última revisão:
170919
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170526
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0178056


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[PMID]:28538147
[Au] Autor:Yang Y; Shi L; Ding Y; Shi Y; Hu HY; Wen Y; Zhang N
[Ad] Endereço:CAS Key Laboratory of Receptor Research, Department of Analytical Chemistry, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China; University of Chinese Academy of Sciences, Beijing, China.
[Ti] Título:Structural and Functional Investigations of the N-Terminal Ubiquitin Binding Region of Usp25.
[So] Source:Biophys J;112(10):2099-2108, 2017 May 23.
[Is] ISSN:1542-0086
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Ubiquitin-specific protease 25 (Usp25) is a deubiquitinase that is involved in multiple biological processes. The N-terminal ubiquitin-binding region (UBR) of Usp25 contains one ubiquitin-associated domain, one small ubiquitin-like modifier (SUMO)-interacting motif and two ubiquitin-interacting motifs. Previous studies suggest that the covalent sumoylation in the UBR of Usp25 impairs its enzymatic activity. Here, we raise the hypothesis that non-covalent binding of SUMO, a prerequisite for efficient sumoylation, will impair Usp25's catalytic activity as well. To test our hypothesis and elucidate the underlying molecular mechanism, we investigated the structure and function of the Usp25 N-terminal UBR. The solution structure of Usp25 is obtained, and the key residues responsible for recognition of ubiquitin and SUMO2 are identified. Our data suggest inhibition of Usp25's catalytic activity upon the non-covalent binding of SUMO2 to the Usp25 SUMO-interacting motif. We also find that SUMO2 can competitively block the interaction between the Usp25 UBR and its ubiquitin substrates. Based on our findings, we have proposed a working model to depict the regulatory role of the Usp25 UBR in the functional display of the enzyme.
[Mh] Termos MeSH primário: Ubiquitina Tiolesterase/metabolismo
Ubiquitina/metabolismo
[Mh] Termos MeSH secundário: Animais
Calorimetria
Cromatografia em Gel
Difusão Dinâmica da Luz
Escherichia coli
Seres Humanos
Camundongos
Modelos Moleculares
Mutação
Ressonância Magnética Nuclear Biomolecular
Ligação Proteica
Domínios Proteicos
Proteínas Modificadoras Pequenas Relacionadas à Ubiquitina/metabolismo
Soluções
Ubiquitina Tiolesterase/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Small Ubiquitin-Related Modifier Proteins); 0 (Solutions); 0 (Ubiquitin); EC 3.1.2.15 (USP25 protein, human); EC 3.1.2.15 (USP25 protein. mouse); EC 3.4.19.12 (Ubiquitin Thiolesterase)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170809
[Lr] Data última revisão:
170809
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170525
[St] Status:MEDLINE



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