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Pesquisa : G02.111.660.871.790.600.925.500 [Categoria DeCS]
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  1 / 1332 MEDLINE  
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[PMID]:29295999
[Au] Autor:Han S; Ren Y; He W; Liu H; Zhi Z; Zhu X; Yang T; Rong Y; Ma B; Purwin TJ; Ouyang Z; Li C; Wang X; Wang X; Yang H; Zheng Y; Aplin AE; Liu J; Shao Y
[Ad] Endereço:Frontier Institute of Science and Technology, and Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, 710049, China.
[Ti] Título:ERK-mediated phosphorylation regulates SOX10 sumoylation and targets expression in mutant BRAF melanoma.
[So] Source:Nat Commun;9(1):28, 2018 01 02.
[Is] ISSN:2041-1723
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:In human mutant BRAF melanoma cells, the stemness transcription factor FOXD3 is rapidly induced by inhibition of ERK1/2 signaling and mediates adaptive resistance to RAF inhibitors. However, the mechanism underlying ERK signaling control of FOXD3 expression remains unknown. Here we show that SOX10 is both necessary and sufficient for RAF inhibitor-induced expression of FOXD3 in mutant BRAF melanoma cells. SOX10 activates the transcription of FOXD3 by binding to a regulatory element in FOXD3 promoter. Phosphorylation of SOX10 by ERK inhibits its transcription activity toward multiple target genes by interfering with the sumoylation of SOX10 at K55, which is essential for its transcription activity. Finally, depletion of SOX10 sensitizes mutant BRAF melanoma cells to RAF inhibitors in vitro and in vivo. Thus, our work discovers a novel phosphorylation-dependent regulatory mechanism of SOX10 transcription activity and completes an ERK1/2/SOX10/FOXD3/ERBB3 axis that mediates adaptive resistance to RAF inhibitors in mutant BRAF melanoma cells.
[Mh] Termos MeSH primário: Regulação Neoplásica da Expressão Gênica/genética
Melanoma/genética
Mutação
Proteínas Proto-Oncogênicas B-raf/genética
Fatores de Transcrição SOXE/genética
Neoplasias Cutâneas/genética
[Mh] Termos MeSH secundário: Animais
Linhagem Celular Tumoral
Inibidores Enzimáticos/farmacologia
MAP Quinases Reguladas por Sinal Extracelular/metabolismo
Feminino
Fatores de Transcrição Forkhead/genética
Fatores de Transcrição Forkhead/metabolismo
Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos
Seres Humanos
Indóis/farmacologia
Melanoma/tratamento farmacológico
Melanoma/metabolismo
Camundongos Endogâmicos BALB C
Camundongos Nus
Fosforilação
Proteínas Proto-Oncogênicas B-raf/metabolismo
Interferência de RNA
Receptor ErbB-3/genética
Receptor ErbB-3/metabolismo
Fatores de Transcrição SOXE/metabolismo
Neoplasias Cutâneas/tratamento farmacológico
Neoplasias Cutâneas/metabolismo
Sulfonamidas/farmacologia
Sumoilação
Ensaios Antitumorais Modelo de Xenoenxerto
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Enzyme Inhibitors); 0 (FOXD3 protein, human); 0 (Forkhead Transcription Factors); 0 (Indoles); 0 (SOX10 protein, human); 0 (SOXE Transcription Factors); 0 (Sulfonamides); 207SMY3FQT (vemurafenib); EC 2.7.10.1 (ERBB3 protein, human); EC 2.7.10.1 (Receptor, ErbB-3); EC 2.7.11.1 (Proto-Oncogene Proteins B-raf); EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180306
[Lr] Data última revisão:
180306
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180104
[St] Status:MEDLINE
[do] DOI:10.1038/s41467-017-02354-x


  2 / 1332 MEDLINE  
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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


  3 / 1332 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


  4 / 1332 MEDLINE  
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[PMID]:29236778
[Au] Autor:Wang C; Zeng N; Liu S; Miao Q; Zhou L; Ge X; Han J; Guo X; Yang H
[Ad] Endereço:Key Laboratory of Animal Epidemiology of the Ministry of Agriculture, College of Veterinary Medicine and State Key Laboratory of Agrobiotechnology, China Agricultural University, Beijing, People's Republic of China.
[Ti] Título:Interaction of porcine reproductive and respiratory syndrome virus proteins with SUMO-conjugating enzyme reveals the SUMOylation of nucleocapsid protein.
[So] Source:PLoS One;12(12):e0189191, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:SUMOylation is a reversible post-translational modification that regulates the function of target protein. In this study, we first predicted by software that the multiple proteins of porcine reproductive and respiratory syndrome virus (PRRSV) could be sumoylated. Next, we confirmed that Nsp1ß, Nsp4, Nsp9, Nsp10 and nucleocapsid (N) protein of PRRSV could interact with the sole SUMO E2 conjugating enzyme Ubc9, and Ubc9 could be co-localized with Nsp1ß, Nsp4, Nsp9 and Nsp10 in the cytoplasm, while with N protein in both the cytoplasm and nucleus. Finally, we demonstrated that N protein could be sumoylated by either SUMO1 or SUMO2/3. In addition, the overexpression of Ubc9 could inhibit viral genomic replication at early period of PRRSV infection and the knockdown of Ubc9 by siRNA could promote the virus replication. These findings reveal the SUMOylation property of PRRSV N protein and the involvement of Ubc9 in PRRSV replication through interaction with multiple proteins of PRRSV. To our knowledge, this is the first study indicating the interplay between SUMO modification system and PRRSV.
[Mh] Termos MeSH primário: Proteínas do Nucleocapsídeo/metabolismo
Vírus da Síndrome Respiratória e Reprodutiva Suína/metabolismo
Sumoilação
[Mh] Termos MeSH secundário: Animais
Vírus da Síndrome Respiratória e Reprodutiva Suína/fisiologia
Suínos
Técnicas do Sistema de Duplo-Híbrido
Replicação Viral
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Nucleocapsid Proteins)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180116
[Lr] Data última revisão:
180116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171214
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0189191


  5 / 1332 MEDLINE  
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[PMID]:27778286
[Au] Autor:Kessler BM; Bursomanno S; McGouran JF; Hickson ID; Liu Y
[Ad] Endereço:Target Discovery Institute, Nuffield Department of Medicine, University of Oxford, Roosevelt Drive, Oxford, OX3 7FZ, UK. benedikt.kessler@ndm.ox.ac.uk.
[Ti] Título:Biochemical and Mass Spectrometry-Based Approaches to Profile SUMOylation in Human Cells.
[So] Source:Methods Mol Biol;1491:131-144, 2017.
[Is] ISSN:1940-6029
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Posttranslational modification of proteins with the small ubiquitin-like modifier (SUMO) regulates protein function in the context of cell cycle and DNA repair. The occurrence of SUMOylation is less frequent as compared to protein modification with ubiquitin, and appears to be controlled by a smaller pool of conjugating and deconjugating enzymes. Mass spectrometry has been instrumental in defining specific as well as proteome-wide views of SUMO-dependent biological processes, and several methodological approaches have been developed in the recent past. Here, we provide an overview of the latest experimental approaches to the study of SUMOylation, and also describe hands-on protocols using a combination of biochemistry and mass spectrometry-based technologies to profile proteins that are SUMOylated in human cells.
[Mh] Termos MeSH primário: Espectrometria de Massas/métodos
Sumoilação
[Mh] Termos MeSH secundário: Reparo do DNA
Seres Humanos
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180116
[Lr] Data última revisão:
180116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161026
[St] Status:MEDLINE


  6 / 1332 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


  7 / 1332 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


  8 / 1332 MEDLINE  
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[PMID]:29048423
[Au] Autor:McManus FP; Lamoliatte F; Thibault P
[Ad] Endereço:Institute for Research in Immunology and Cancer, Québec, Canada.
[Ti] Título:Identification of cross talk between SUMOylation and ubiquitylation using a sequential peptide immunopurification approach.
[So] Source:Nat Protoc;12(11):2342-2358, 2017 Nov.
[Is] ISSN:1750-2799
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Ubiquitin and ubiquitin-like modifiers (UBLs) such as small ubiquitin-like modifier (SUMO) can act as antagonists to one another by competing to occupy similar residues in the proteome. In addition, SUMO and ubiquitin can be coupled to each other at key lysine residues to form highly branched protein networks. The interplay between these modifications governs important biological processes such as double-strand break repair and meiotic recombination. We recently developed an approach that permits the identification of proteins that are modified by both SUMOylation and ubiquitylation. This protocol requires cells that express a mutant 6×His-SUMO3m protein that has had its C terminus modified from QQQTGG to RNQTGG, enabling the purification of SUMOylated peptides and their identification by tandem mass spectrometry (MS/MS). Cells are lysed under denaturing conditions, and the SUMOylated proteins are purified on nickel-nitrilotriacetic acid (Ni-NTA) resin via the 6×His on the SUMO3m construct. After on-bead digestion using trypsin, ubiquitylated peptides are enriched by immunoprecipitation, and the flow-through from this step is subjected to anti-SUMO immunoprecipitation. The SUMOylated peptides are fractionated on strong cation exchange (SCX) StageTips to enhance the coverage of the SUMO proteome. The ubiquitylated and SUMOylated peptides are analyzed separately by liquid chromatography (LC)-MS/MS and identified with MaxQuant. We demonstrate how this approach can be used to identify temporal changes in SUMOylated and ubiquitylated proteins in response to, for instance, heat shock and proteasome inhibition. The procedure requires 3 d when starting from cell pellets and yields >8,000 SUMO sites and >3,500 ubiquitin sites from 16 mg of cell extract.
[Mh] Termos MeSH primário: Imunoprecipitação/métodos
Peptídeos/metabolismo
Sumoilação
Ubiquitinação
[Mh] Termos MeSH secundário: Linhagem Celular
Seres Humanos
Peptídeos/imunologia
Peptídeos/isolamento & purificação
Ubiquitinas/genética
Ubiquitinas/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Peptides); 0 (SUMO3 protein, human); 0 (Ubiquitins)
[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:171020
[St] Status:MEDLINE
[do] DOI:10.1038/nprot.2017.105


  9 / 1332 MEDLINE  
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[PMID]:29045470
[Au] Autor:Surana P; Gowda CM; Tripathi V; Broday L; Das R
[Ad] Endereço:National Centre for Biological Sciences, Tata Institute of Fundamental Research, Bengaluru, India.
[Ti] Título:Structural and functional analysis of SMO-1, the SUMO homolog in Caenorhabditis elegans.
[So] Source:PLoS One;12(10):e0186622, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:SUMO proteins are important post-translational modifiers involved in multiple cellular pathways in eukaryotes, especially during the different developmental stages in multicellular organisms. The nematode C. elegans is a well known model system for studying metazoan development and has a single SUMO homolog, SMO-1. Interestingly, SMO-1 modification is linked to embryogenesis and development in the nematode. However, high-resolution information about SMO-1 and the mechanism of its conjugation is lacking. In this work, we report the high-resolution three dimensional structure of SMO-1 solved by NMR spectroscopy. SMO-1 has flexible N-terminal and C-terminal tails on either side of a rigid beta-grasp folded core. While the sequence of SMO-1 is more similar to SUMO1, the electrostatic surface features of SMO-1 resemble more with SUMO2/3. SMO-1 can bind to typical SUMO Interacting Motifs (SIMs). SMO-1 can also conjugate to a typical SUMOylation consensus site as well as to its natural substrate HMR-1. Poly-SMO-1 chains were observed in-vitro even though SMO-1 lacks any consensus SUMOylation site. Typical deSUMOylation enzymes like Senp2 can cleave the poly-SMO-1 chains. Despite being a single gene, the SMO-1 structure allows it to function in a large repertoire of signaling pathways involving SUMO in C. elegans. Structural and functional features of SMO-1 studies described here will be useful to understand its role in development.
[Mh] Termos MeSH primário: Proteínas de Caenorhabditis elegans/química
Proteínas de Caenorhabditis elegans/metabolismo
Caenorhabditis elegans/metabolismo
Proteína SUMO-1/metabolismo
Homologia de Sequência de Aminoácidos
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Animais
Caderinas/metabolismo
Espectroscopia de Ressonância Magnética
Modelos Moleculares
Ligação Proteica
Domínios e Motivos de Interação entre Proteínas
Proteína SUMO-1/química
Soluções
Eletricidade Estática
Sumoilação
Fatores de Tempo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cadherins); 0 (Caenorhabditis elegans Proteins); 0 (SUMO-1 Protein); 0 (Solutions)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171031
[Lr] Data última revisão:
171031
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171019
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0186622


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[PMID]:28981631
[Au] Autor:Han C; Zhao R; Kroger J; He J; Wani G; Wang QE; Wani AA
[Ad] Endereço:Department of Radiology.
[Ti] Título:UV radiation-induced SUMOylation of DDB2 regulates nucleotide excision repair.
[So] Source:Carcinogenesis;38(10):976-985, 2017 Oct 01.
[Is] ISSN:1460-2180
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Subunit 2 of DNA damage-binding protein complex (DDB2) is an early sensor of nucleotide excision repair (NER) pathway for eliminating DNA damage induced by UV radiation (UVR) and cisplatin treatments of mammalian cells. DDB2 is modified by ubiquitin and poly(ADP-ribose) (PAR) in response to UVR, and these modifications play a crucial role in regulating NER. Here, using immuno-analysis of irradiated cell extracts, we have identified multiple post-irradiation modifications of DDB2 protein. Interestingly, although the DNA lesions induced by both UVR and cisplatin are corrected by NER, only the UV irradiation, but not the cisplatin treatment, induces any discernable DDB2 modifications. We, for the first time, show that the appearance of UVR-induced DDB2 modifications depend on the binding of DDB2 to the damaged chromatin and the participation of functionally active 26S proteasome. The in vitro and in vivo analysis revealed that SUMO-1 conjugations comprise a significant portion of these UVR-induced DDB2 modifications. Mapping of SUMO-modified sites demonstrated that UVR-induced SUMOylation occurs on Lys-309 residue of DDB2 protein. Mutation of Lys-309 to Arg-309 diminished the DDB2 SUMOylation observable both in vitro and in vivo. Moreover, K309R mutated DDB2 lost its function of recruiting XPC to the DNA damage sites, as well as the ability to repair cyclobutane pyrimidine dimers following cellular UV irradiation. Taken together, our results indicate that DDB2 is modified by SUMOylation upon UV irradiation, and this post-translational modification plays an important role in the initial recognition and processing of UVR-induced DNA damage occurring within the context of chromatin.
[Mh] Termos MeSH primário: Reparo do DNA/efeitos da radiação
Proteínas de Ligação a DNA/metabolismo
Sumoilação/efeitos da radiação
[Mh] Termos MeSH secundário: Cromatina/metabolismo
Cromatina/efeitos da radiação
Cisplatino/farmacologia
Reparo do DNA/efeitos dos fármacos
Reparo do DNA/fisiologia
Proteínas de Ligação a DNA/genética
Células HeLa
Seres Humanos
Lisina/metabolismo
Complexo de Endopeptidases do Proteassoma/metabolismo
Dímeros de Pirimidina/genética
Dímeros de Pirimidina/metabolismo
Sumoilação/efeitos dos fármacos
Raios Ultravioleta
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Chromatin); 0 (DDB2 protein, human); 0 (DNA-Binding Proteins); 0 (Pyrimidine Dimers); 156533-34-5 (XPC protein, human); EC 3.4.25.1 (Proteasome Endopeptidase Complex); EC 3.4.99.- (ATP dependent 26S protease); K3Z4F929H6 (Lysine); Q20Q21Q62J (Cisplatin)
[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:171006
[St] Status:MEDLINE
[do] DOI:10.1093/carcin/bgx076



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