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Pesquisa : D08.811.464.938.750.656 [Categoria DeCS]
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  1 / 174 MEDLINE  
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[PMID]:28604676
[Au] Autor:Wang YJ; Bian Y; Luo J; Lu M; Xiong Y; Guo SY; Yin HY; Lin X; Li Q; Chang CCY; Chang TY; Li BL; Song BL
[Ad] Endereço:The State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue-Yang Road, Shanghai 200031, China.
[Ti] Título:Cholesterol and fatty acids regulate cysteine ubiquitylation of ACAT2 through competitive oxidation.
[So] Source:Nat Cell Biol;19(7):808-819, 2017 Jul.
[Is] ISSN:1476-4679
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Ubiquitin linkage to cysteine is an unconventional modification targeting protein for degradation. However, the physiological regulation of cysteine ubiquitylation is still mysterious. Here we found that ACAT2, a cellular enzyme converting cholesterol and fatty acid to cholesteryl esters, was ubiquitylated on Cys277 for degradation when the lipid level was low. gp78-Insigs catalysed Lys48-linked polyubiquitylation on this Cys277. A high concentration of cholesterol and fatty acid, however, induced cellular reactive oxygen species (ROS) that oxidized Cys277, resulting in ACAT2 stabilization and subsequently elevated cholesteryl esters. Furthermore, ACAT2 knockout mice were more susceptible to high-fat diet-associated insulin resistance. By contrast, expression of a constitutively stable form of ACAT2 (C277A) resulted in higher insulin sensitivity. Together, these data indicate that lipid-induced stabilization of ACAT2 ameliorates lipotoxicity from excessive cholesterol and fatty acid. This unconventional cysteine ubiquitylation of ACAT2 constitutes an important mechanism for sensing lipid-overload-induced ROS and fine-tuning lipid homeostasis.
[Mh] Termos MeSH primário: Colesterol/metabolismo
Ácidos Graxos/metabolismo
Fígado/enzimologia
Esterol O-Aciltransferase/metabolismo
[Mh] Termos MeSH secundário: Animais
Células CHO
Ésteres do Colesterol/metabolismo
Cricetulus
Cisteína
Dieta Hiperlipídica
Modelos Animais de Doenças
Genótipo
Células Hep G2
Homeostase
Seres Humanos
Resistência à Insulina
Masculino
Camundongos Endogâmicos C57BL
Camundongos Knockout
Oxirredução
Fenótipo
Proteólise
Interferência de RNA
Espécies Reativas de Oxigênio/metabolismo
Receptores do Fator Autócrino de Motilidade/genética
Receptores do Fator Autócrino de Motilidade/metabolismo
Esterol O-Aciltransferase/deficiência
Esterol O-Aciltransferase/genética
Fatores de Tempo
Transfecção
Ubiquitinação
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cholesterol Esters); 0 (Fatty Acids); 0 (Reactive Oxygen Species); 97C5T2UQ7J (Cholesterol); EC 2.3.1.26 (Sterol O-Acyltransferase); EC 2.3.1.26 (sterol O-acyltransferase 2); EC 2.3.2.27 (Amfr protein, mouse); EC 2.3.2.27 (Receptors, Autocrine Motility Factor); K848JZ4886 (Cysteine)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170913
[Lr] Data última revisão:
170913
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170613
[St] Status:MEDLINE
[do] DOI:10.1038/ncb3551


  2 / 174 MEDLINE  
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[PMID]:28536268
[Au] Autor:Sopha P; Ren HY; Grove DE; Cyr DM
[Ad] Endereço:From the Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599 and pattarawut@cgi.ac.th.
[Ti] Título:Endoplasmic reticulum stress-induced degradation of DNAJB12 stimulates BOK accumulation and primes cancer cells for apoptosis.
[So] Source:J Biol Chem;292(28):11792-11803, 2017 Jul 14.
[Is] ISSN:1083-351X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:DNAJB12 (JB12) is an endoplasmic reticulum (ER)-associated Hsp40 family protein that recruits Hsp70 to the ER surface to coordinate the function of ER-associated and cytosolic chaperone systems in protein quality control. Hsp70 is stress-inducible, but paradoxically, we report here that JB12 was degraded by the proteasome during severe ER stress. Destabilized JB12 was degraded by ER-associated degradation complexes that contained HERP, Sel1L, and gp78. JB12 was the only ER-associated chaperone that was destabilized by reductive stress. JB12 knockdown by siRNA led to the induction of caspase processing but not the unfolded protein response. ER stress-induced apoptosis is regulated by the highly labile and ER-associated BCL-2 family member BOK, which is controlled at the level of protein stability by ER-associated degradation components. We found that JB12 was required in human hepatoma cell line 7 (Huh-7) liver cancer cells to maintain BOK at low levels, and BOK was detected in complexes with JB12 and gp78. Depletion of JB12 during reductive stress or by shRNA from Huh-7 cells was associated with accumulation of BOK and activation of Caspase 3, 7, and 9. The absence of JB12 sensitized Huh-7 to death caused by proteotoxic agents and the proapoptotic chemotherapeutic LCL-161. In summary, JB12 is a stress-sensitive Hsp40 whose degradation during severe ER stress provides a mechanism to promote BOK accumulation and induction of apoptosis.
[Mh] Termos MeSH primário: Apoptose
Carcinoma Hepatocelular/metabolismo
Estresse do Retículo Endoplasmático
Proteínas de Choque Térmico HSP40/metabolismo
Proteínas de Neoplasias/metabolismo
Complexo de Endopeptidases do Proteassoma/metabolismo
Proteínas Proto-Oncogênicas c-bcl-2/metabolismo
[Mh] Termos MeSH secundário: Substituição de Aminoácidos
Animais
Antineoplásicos/farmacologia
Apoptose/efeitos dos fármacos
Células COS
Carcinoma Hepatocelular/tratamento farmacológico
Carcinoma Hepatocelular/patologia
Linhagem Celular Tumoral
Cercopithecus aethiops
Resistência a Medicamentos Antineoplásicos
Estresse do Retículo Endoplasmático/efeitos dos fármacos
Células HEK293
Proteínas de Choque Térmico HSP40/antagonistas & inibidores
Proteínas de Choque Térmico HSP40/genética
Seres Humanos
Neoplasias Hepáticas/tratamento farmacológico
Neoplasias Hepáticas/metabolismo
Neoplasias Hepáticas/patologia
Mutação
Proteínas de Neoplasias/antagonistas & inibidores
Complexo de Endopeptidases do Proteassoma/efeitos dos fármacos
Estabilidade Proteica/efeitos dos fármacos
Proteólise/efeitos dos fármacos
Proteínas Proto-Oncogênicas c-bcl-2/antagonistas & inibidores
Interferência de RNA/efeitos dos fármacos
Receptores do Fator Autócrino de Motilidade/metabolismo
Proteínas Recombinantes de Fusão/química
Proteínas Recombinantes de Fusão/metabolismo
Tiazóis/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (BOK protein, human); 0 (DNAJB12 protein, human); 0 (HSP40 Heat-Shock Proteins); 0 (LCL161); 0 (Neoplasm Proteins); 0 (Proto-Oncogene Proteins c-bcl-2); 0 (Recombinant Fusion Proteins); 0 (Thiazoles); EC 2.3.2.27 (AMFR protein, human); EC 2.3.2.27 (Receptors, Autocrine Motility Factor); EC 3.4.25.1 (Proteasome Endopeptidase Complex)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170803
[Lr] Data última revisão:
170803
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170525
[St] Status:MEDLINE
[do] DOI:10.1074/jbc.M117.785113


  3 / 174 MEDLINE  
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[PMID]:28301499
[Au] Autor:Khodayari N; Wang RL; Marek G; Krotova K; Kirst M; Liu C; Rouhani F; Brantly M
[Ad] Endereço:Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of Florida, Gainesville, Florida, United States.
[Ti] Título:SVIP regulates Z variant alpha-1 antitrypsin retro-translocation by inhibiting ubiquitin ligase gp78.
[So] Source:PLoS One;12(3):e0172983, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Alpha-1 antitrypsin deficiency (AATD) is an inherited disorder characterized by early-onset emphysema and liver disease. The most common disease-causing mutation is a single amino acid substitution (Glu/Lys) at amino acid 342 of the mature protein, resulting in disruption of the 290-342 salt bridge (an electrophoretic abnormality defining the mutation [Z allele, or ZAAT]), protein misfolding, polymerization, and accumulation in the endoplasmic reticulum of hepatocytes and monocytes. The Z allele causes a toxic gain of function, and the E3 ubiquitin ligase gp78 promotes degradation and increased solubility of endogenous ZAAT. We hypothesized that the accumulation of ZAAT is influenced by modulation of gp78 E3 ligase and SVIP (small VCP-interacting protein) interaction with p97/VCP in ZAAT-expressing hepatocytes. We showed that the SVIP inhibitory effect on ERAD due to overexpression causes the accumulation of ZAAT in a human Z hepatocyte-like cell line (AT01). Overexpression of gp78, as well as SVIP suppression, induces gp78-VCP/p97 interaction in AT01 cells. This interaction leads to retro-translocation of ZAAT and reduction of the SVIP inhibitory role in ERAD. In this context, overexpression of gp78 or SVIP suppression may eliminate the toxic gain of function associated with polymerization of ZAAT, thus providing a potential new therapeutic approach to the treatment of AATD.
[Mh] Termos MeSH primário: Proteínas de Transporte/fisiologia
Proteínas de Membrana/fisiologia
Receptores do Fator Autócrino de Motilidade/antagonistas & inibidores
alfa 1-Antitripsina/metabolismo
[Mh] Termos MeSH secundário: Linhagem Celular
Estresse do Retículo Endoplasmático
Seres Humanos
Mutação
Transporte Proteico
Reação em Cadeia da Polimerase em Tempo Real
alfa 1-Antitripsina/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Carrier Proteins); 0 (Membrane Proteins); 0 (SVIP protein, human); 0 (alpha 1-Antitrypsin); EC 2.3.2.27 (AMFR protein, human); EC 2.3.2.27 (Receptors, Autocrine Motility Factor)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170907
[Lr] Data última revisão:
170907
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170317
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0172983


  4 / 174 MEDLINE  
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[PMID]:27387505
[Au] Autor:Zhao Y; Zhang T; Huo H; Ye Y; Liu Y
[Ad] Endereço:From the School of Life Science and Technology, ShanghaiTech University, 100 Haike Rd., Shanghai 201210, China and.
[Ti] Título:Lunapark Is a Component of a Ubiquitin Ligase Complex Localized to the Endoplasmic Reticulum Three-way Junctions.
[So] Source:J Biol Chem;291(35):18252-62, 2016 08 26.
[Is] ISSN:1083-351X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The endoplasmic reticulum (ER) network comprises sheets and tubules that are connected by dynamic three-way junctions. Lunapark (Lnp) localizes to and stabilizes ER three-way junctions by antagonizing the small GTPase Atlastin, but how Lnp shapes the ER network is unclear. Here, we used an affinity purification approach and mass spectrometry to identify Lnp as an interacting partner of the ER protein quality control ubiquitin ligase gp78. Accordingly, Lnp purified from mammalian cells has a ubiquitin ligase activity in vitro Intriguingly, biochemical analyses show that this activity can be attributed not only to associated ubiquitin ligase, but also to an intrinsic ubiquitin ligase activity borne by Lnp itself. This activity is contained in the N-terminal 45 amino acids of Lnp although this segment does not share homology to any known ubiquitin ligase motifs. Despite its interaction with gp78, Lnp does not seem to have a broad function in degradation of misfolded ER proteins. On the other hand, the N-terminal ubiquitin ligase-bearing motif is required for the ER three-way junction localization of Lnp. Our study identifies a new type of ubiquitin ligase and reveals a potential link between ubiquitin and ER morphology regulation.
[Mh] Termos MeSH primário: Retículo Endoplasmático/metabolismo
Proteínas de Homeodomínio/metabolismo
Receptores do Fator Autócrino de Motilidade/metabolismo
[Mh] Termos MeSH secundário: Motivos de Aminoácidos
Animais
Células COS
Cercopithecus aethiops
Retículo Endoplasmático/genética
Proteínas de Ligação ao GTP/genética
Proteínas de Ligação ao GTP/metabolismo
Células HeLa
Proteínas de Homeodomínio/genética
Seres Humanos
Proteínas de Membrana/genética
Proteínas de Membrana/metabolismo
Transporte Proteico
Receptores do Fator Autócrino de Motilidade/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T; RESEARCH SUPPORT, N.I.H., INTRAMURAL
[Nm] Nome de substância:
0 (Homeodomain Proteins); 0 (KIAA1715 protein, human); 0 (Membrane Proteins); EC 2.3.2.27 (AMFR protein, human); EC 2.3.2.27 (Receptors, Autocrine Motility Factor); EC 3.6.1.- (ATL1 protein, human); EC 3.6.1.- (GTP-Binding Proteins)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:171121
[Lr] Data última revisão:
171121
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160709
[St] Status:MEDLINE
[do] DOI:10.1074/jbc.M116.737783


  5 / 174 MEDLINE  
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[PMID]:27320797
[Au] Autor:Kim SM; Wang Y; Nabavi N; Liu Y; Correia MA
[Ad] Endereço:a Department of Cellular & Molecular Pharmacology , University of California San Francisco , San Francisco , CA , USA ;
[Ti] Título:Hepatic cytochromes P450: structural degrons and barcodes, posttranslational modifications and cellular adapters in the ERAD-endgame.
[So] Source:Drug Metab Rev;48(3):405-33, 2016 Aug.
[Is] ISSN:1097-9883
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The endoplasmic reticulum (ER)-anchored hepatic cytochromes P450 (P450s) are enzymes that metabolize endo- and xenobiotics i.e. drugs, carcinogens, toxins, natural and chemical products. These agents modulate liver P450 content through increased synthesis or reduction via inactivation and/or proteolytic degradation, resulting in clinically significant drug-drug interactions. P450 proteolytic degradation occurs via ER-associated degradation (ERAD) involving either of two distinct routes: Ubiquitin (Ub)-dependent 26S proteasomal degradation (ERAD/UPD) or autophagic lysosomal degradation (ERAD/ALD). CYP3A4, the major human liver/intestinal P450, and the fast-turnover CYP2E1 species are degraded via ERAD/UPD entailing multisite protein phosphorylation and subsequent ubiquitination by gp78 and CHIP E3 Ub-ligases. We are gaining insight into the nature of the structural determinants involved in CYP3A4 and CYP2E1 molecular recognition in ERAD/UPD [i.e. K48-linked polyUb chains and linear and/or "conformational" phosphodegrons consisting either of consecutive sequences on surface loops and/or disordered regions, or structurally-assembled surface clusters of negatively charged acidic (Asp/Glu) and phosphorylated (Ser/Thr) residues, within or vicinal to which, Lys-residues are targeted for ubiquitination]. Structural inspection of select human liver P450s reveals that such linear or conformational phosphodegrons may indeed be a common P450-ERAD/UPD feature. By contrast, although many P450s such as the slow-turnover CYP2E1 species and rat liver CYP2B1 and CYP2C11 are degraded via ERAD/ALD, little is known about the mechanism of their ALD-targeting. On the basis of our current knowledge of ALD-substrate targeting, we propose a tripartite conjunction of K63-linked Ub-chains, P450 structural "LIR" motifs and selective cellular "cargo receptors" as plausible P450-ALD determinants.
[Mh] Termos MeSH primário: Sistema Enzimático do Citocromo P-450/metabolismo
Degradação Associada com o Retículo Endoplasmático
Fígado/enzimologia
Fígado/metabolismo
Proteólise
[Mh] Termos MeSH secundário: Animais
Seres Humanos
Fígado/citologia
Lisossomos/metabolismo
Modelos Biológicos
Receptores do Fator Autócrino de Motilidade/metabolismo
Ubiquitina-Proteína Ligases/metabolismo
Ubiquitinação
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
9035-51-2 (Cytochrome P-450 Enzyme System); EC 2.3.2.27 (AMFR protein, human); EC 2.3.2.27 (Receptors, Autocrine Motility Factor); EC 2.3.2.27 (STUB1 protein, human); EC 2.3.2.27 (Ubiquitin-Protein Ligases)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170830
[Lr] Data última revisão:
170830
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160621
[St] Status:MEDLINE
[do] DOI:10.1080/03602532.2016.1195403


  6 / 174 MEDLINE  
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[PMID]:27173213
[Au] Autor:Chen CZ; Zhu YN; Chai ML; Dai LS; Gao Y; Jiang H; Zhang LJ; Ding Y; Liu SY; Li QY; Lu WF; Zhang JB
[Ad] Endereço:Laboratory Animal Center, College of Animal Sciences, Jilin University, Changchun, China.
[Ti] Título:AMFR gene silencing inhibits the differentiation of porcine preadipocytes.
[So] Source:Genet Mol Res;15(2), 2016 Apr 07.
[Is] ISSN:1676-5680
[Cp] País de publicação:Brazil
[La] Idioma:eng
[Ab] Resumo:Our study clarifies the role of the autocrine motility factor receptor (AMFR) gene in porcine preadipocyte differentiation. AMFR-siRNA was transfected into porcine preadipocytes and the preadipocytes were induced to differentiation. Subsequently, qRT-PCR was conducted to examine changes in mRNA expression of a series of genes in porcine preadipocytes, including AMFR, sterol-regulatory element-binding protein-1a (SREBP1a), SREBP2, insulin-induced gene 1 (Insig1), and Insig2. Expression changes in the mRNA of genes regulating adipocyte differentiation were also analyzed using qRT-PCR, including peroxisome proliferator-activated receptor gamma (PPARγ), CCAAT/enhancer-binding protein alpha (C/EBPα), and Kruppel-like factor 2 (KLF2). Western blot analysis was conducted to examine the changes in AMFR protein expression in porcine preadipocytes. Additionally, morphological changes in differentiated porcine preadipocytes were examined by oil red O staining, and changes in optical density (OD) values were measured using an ultraviolet spectrophotometer. At 24 h after transfection with AMFR-siRNA, AMFR mRNA expression significantly reduced (P < 0.01), and AMFR protein expression markedly decreased (P < 0.05). The mRNA expression of SREBP1a, SREBP2, Insig1, and C/EBPα was significantly reduced (P < 0.01), whereas the expression of KLF2 mRNA was significantly elevated (P < 0.01). After induction of preadipocyte differentiation, the number of lipid droplets decreased in the AMFR-silenced group, and the OD value markedly reduced (P < 0.05). In addition, the expression of C/EBPα mRNA significantly decreased (P < 0.05), whereas the expression of KLF2 mRNA considerably increased (P < 0.05). Taken together, silencing of the AMFR gene inhibits the differentiation of porcine preadipocytes.
[Mh] Termos MeSH primário: Adipócitos/metabolismo
Diferenciação Celular
Receptores do Fator Autócrino de Motilidade/metabolismo
[Mh] Termos MeSH secundário: Adipócitos/citologia
Animais
Proteína alfa Estimuladora de Ligação a CCAAT/genética
Proteína alfa Estimuladora de Ligação a CCAAT/metabolismo
Células Cultivadas
Inativação Gênica
Fatores de Transcrição Kruppel-Like/genética
Fatores de Transcrição Kruppel-Like/metabolismo
PPAR gama/genética
PPAR gama/metabolismo
Receptores do Fator Autócrino de Motilidade/genética
Proteína de Ligação a Elemento Regulador de Esterol 1/genética
Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo
Proteína de Ligação a Elemento Regulador de Esterol 2/genética
Proteína de Ligação a Elemento Regulador de Esterol 2/metabolismo
Suínos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (CCAAT-Enhancer-Binding Protein-alpha); 0 (Kruppel-Like Transcription Factors); 0 (PPAR gamma); 0 (Sterol Regulatory Element Binding Protein 1); 0 (Sterol Regulatory Element Binding Protein 2); EC 2.3.2.27 (Receptors, Autocrine Motility Factor)
[Em] Mês de entrada:1702
[Cu] Atualização por classe:170206
[Lr] Data última revisão:
170206
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160514
[St] Status:MEDLINE
[do] DOI:10.4238/gmr.15027354


  7 / 174 MEDLINE  
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[PMID]:27067047
[Au] Autor:Gao F; Shang Y; Liu W; Li W
[Ad] Endereço:The State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, PR China.
[Ti] Título:The linkage specificity determination of Ube2g2-gp78 mediated polyubiquitination.
[So] Source:Biochem Biophys Res Commun;473(4):1139-1143, 2016 05 13.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Polyubiquitin chain linkage specificity or topology is essential for its role in diverse cellular processes. Previous studies pay more attentions to the linkage specificity of the first ubiquitin moieties, whereas, little is known about the editing mechanism of linkage specificity in longer polyubiquitin chains. gp78 and its cognate E2-Ube2g2 catalyze lysine48 (K48)-linked polyubiquitin chains to promote the degradation of targeted proteins. Here, we show that the linkage specificity of the entire polyubiquitin chain is determined by the conjugation manner of the first ubiquitin molecule but not the following ones. Further study discovered that the gp78 CUE domain works as a proofreading machine during the growth of K48-linked polyubiquitin chains to ensure the linkage specificity. Together, our studies uncover a novel mechanism underlying the linkage specificity determination of longer polyubiquitin chains.
[Mh] Termos MeSH primário: Poliubiquitina/síntese química
Receptores do Fator Autócrino de Motilidade/química
Enzimas de Conjugação de Ubiquitina/química
[Mh] Termos MeSH secundário: Substituição de Aminoácidos
Sítios de Ligação
Ativação Enzimática
Ligação Proteica
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
120904-94-1 (Polyubiquitin); EC 2.3.2.23 (UBE2G2 protein, human); EC 2.3.2.23 (Ubiquitin-Conjugating Enzymes); EC 2.3.2.27 (AMFR protein, human); EC 2.3.2.27 (Receptors, Autocrine Motility Factor)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:171117
[Lr] Data última revisão:
171117
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160413
[St] Status:MEDLINE


  8 / 174 MEDLINE  
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[PMID]:26743086
[Au] Autor:Mukherjee R; Chakrabarti O
[Ad] Endereço:Biophysics & Structural Genomics Division, Saha Institute of Nuclear Physics, 1/AF Bidhannagar, Kolkata 700064, India.
[Ti] Título:Ubiquitin-mediated regulation of the E3 ligase GP78 by MGRN1 in trans affects mitochondrial homeostasis.
[So] Source:J Cell Sci;129(4):757-73, 2016 Feb 15.
[Is] ISSN:1477-9137
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Cellular quality control provides an efficient surveillance system to regulate mitochondrial turnover. This study elucidates a new interaction between the cytosolic E3 ligase mahogunin RING finger 1 (MGRN1) and the endoplasmic reticulum (ER) ubiquitin E3 ligase GP78 (also known as AMFR). Loss of Mgrn1 function has been implicated in late-onset spongiform neurodegeneration and congenital heart defects, among several developmental defects. Here, we show that MGRN1 ubiquitylates GP78 in trans through non-canonical K11 linkages. This helps maintain constitutively low levels of GP78 in healthy cells, in turn downregulating mitophagy. GP78, however, does not regulate MGRN1. When mitochondria are stressed, cytosolic Ca(2+) increases. This leads to a reduced interaction between MGRN1 and GP78 and its compromised ubiquitylation. Chelating Ca(2+) restores association between the two ligases and the in trans ubiquitylation. Catalytic inactivation of MGRN1 results in elevated levels of GP78 and a consequential increase in the initiation of mitophagy. This is important because functional depletion of MGRN1 by the membrane-associated disease-causing prion protein (Ctm)PrP affects polyubiquitylation and degradation of GP78, also leading to an increase in mitophagy events. This suggests that MGRN1 participates in mitochondrial quality control and could contribute to neurodegeneration in a subset of (Ctm)PrP-mediated prion diseases.
[Mh] Termos MeSH primário: Mitocôndrias/metabolismo
Receptores do Fator Autócrino de Motilidade/metabolismo
Ubiquitina-Proteína Ligases/fisiologia
Ubiquitina/metabolismo
Ubiquitinação
[Mh] Termos MeSH secundário: Animais
Células HeLa
Homeostase
Seres Humanos
Camundongos
Degradação Mitocondrial
Complexo de Endopeptidases do Proteassoma/metabolismo
Proteólise
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Ubiquitin); EC 2.3.2.27 (AMFR protein, human); EC 2.3.2.27 (MGRN1 protein, human); EC 2.3.2.27 (Receptors, Autocrine Motility Factor); EC 2.3.2.27 (Ubiquitin-Protein Ligases); EC 3.4.25.1 (Proteasome Endopeptidase Complex)
[Em] Mês de entrada:1612
[Cu] Atualização por classe:161230
[Lr] Data última revisão:
161230
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160109
[St] Status:MEDLINE
[do] DOI:10.1242/jcs.176537


  9 / 174 MEDLINE  
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[PMID]:25689831
[Au] Autor:Qundos U; Drobin K; Mattsson C; Hong MG; Sjöberg R; Forsström B; Solomon D; Uhlén M; Nilsson P; Michaëlsson K; Schwenk JM
[Ad] Endereço:Affinity Proteomics, SciLifeLab, KTH-Royal Institute of Technology, Solna, Sweden.
[Ti] Título:Affinity proteomics discovers decreased levels of AMFR in plasma from Osteoporosis patients.
[So] Source:Proteomics Clin Appl;10(6):681-90, 2016 06.
[Is] ISSN:1862-8354
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:PURPOSE: Affinity proteomic approaches by antibody bead arrays enable multiplexed analysis of proteins in body fluids. In the presented study, we investigated blood plasma within osteoporosis to discovery differential protein profiles and to propose novel biomarkers candidates for subsequent studies. EXPERIMENTAL DESIGN: Starting with 4608 antibodies and plasma samples from 22 women for an untargeted screening, a set of 72 proteins were suggested for further analysis. Complementing these with targets from literature and other studies, a targeted bead array of 180 antibodies was built to profile for 92 proteins in plasma samples of 180 women from two independent population-based studies. RESULTS: Differential profiles between osteoporosis patients and matched controls were discovered for 12 proteins in at least one of the two study sets. Among these targets, the levels of autocrine motility factor receptor (AMFR) were concordantly lower in plasma of female osteoporosis patients. Subsequently, verification of anti-AMFR antibody selectivity was conducted using high-density peptide and protein arrays, and Western blotting. CONCLUSIONS AND CLINICAL RELEVANCE: Further validation in additional study sets will be needed to determine the clinical value of the observed decrease in AMFR plasma levels in osteoporosis patients, but AMFR may aid our understanding of disease mechanisms and could support existing tools for diagnosis and monitoring of patient mobility within osteoporosis.
[Mh] Termos MeSH primário: Osteoporose/diagnóstico
Proteômica/métodos
Receptores do Fator Autócrino de Motilidade/genética
[Mh] Termos MeSH secundário: Idoso
Sequência de Aminoácidos
Anticorpos/química
Especificidade de Anticorpos
Biomarcadores/sangue
Estudos de Casos e Controles
Feminino
Expressão Gênica
Seres Humanos
Meia-Idade
Osteoporose/sangue
Osteoporose/genética
Análise Serial de Proteínas
Receptores do Fator Autócrino de Motilidade/sangue
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antibodies); 0 (Biomarkers); EC 2.3.2.27 (AMFR protein, human); EC 2.3.2.27 (Receptors, Autocrine Motility Factor)
[Em] Mês de entrada:1704
[Cu] Atualização por classe:170421
[Lr] Data última revisão:
170421
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150218
[St] Status:MEDLINE
[do] DOI:10.1002/prca.201400167


  10 / 174 MEDLINE  
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[PMID]:26459914
[Au] Autor:Tian K; Zhong W; Zheng X; Zhang J; Liu P; Zhang W; Liu H
[Ad] Endereço:Department of Orthopaedics, First Affiliated Hospital, Institute of Cancer Stem Cell, Dalian Medical University, Dalian 116044, China.
[Ti] Título:Neuroleukin/Autocrine Motility Factor Receptor Pathway Promotes Proliferation of Articular Chondrocytes through Activation of AKT and Smad2/3.
[So] Source:Sci Rep;5:15101, 2015 Oct 13.
[Is] ISSN:2045-2322
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Cartilage defect is an intractable clinical problem. Therapeutic strategies for cartilage repair are far from optimal due to poor proliferation capacity of chondrocytes. Autologous chondrocyte implantation is a cell based therapy that uses in vitro amplified healthy chondrocytes from the patient. However, chondrocyte dedifferentiation during in vitro culture limits its application. Neuroleukin (NLK) is a multifunctional protein that stimulates cell growth and migration, together with its receptor autocrine motility factor receptor (AMFR, also called gp78). We investigated expression of NLK and AMFR/gp78 during cartilage development in vivo and in cultured articular chondrocytes in vitro, and found the pair associates with chondrocyte proliferation and differentiation. While applied to isolated articular chondrocytes, NLK promotes cell proliferation and secretion of type II collagen, a marker of proliferating chondrocytes. Further work demonstrates that NLK up regulates pAKT and pSmad2/3, but down regulates pSmad1/5. In animals, NLK treatment also promotes chondrocyte proliferation while inhibits terminal differentiation, leading to expanded proliferating zone but decreased prehypertrophic and hypertrophic zones in the growth plate region. NLK is therefore a candidate factor that can be applied in the treatment of cartilage defects.
[Mh] Termos MeSH primário: Cartilagem Articular/citologia
Condrócitos/metabolismo
Glucose-6-Fosfato Isomerase/metabolismo
Proteínas Proto-Oncogênicas c-akt/metabolismo
Receptores do Fator Autócrino de Motilidade/metabolismo
Transdução de Sinais
Proteína Smad2/metabolismo
Proteína Smad3/metabolismo
[Mh] Termos MeSH secundário: Animais
Proliferação Celular
Expressão Gênica
Glucose-6-Fosfato Isomerase/genética
Lâmina de Crescimento/metabolismo
Fenótipo
Fosforilação
Ratos
Receptores do Fator Autócrino de Motilidade/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Smad2 Protein); 0 (Smad3 Protein); EC 2.3.2.27 (Receptors, Autocrine Motility Factor); EC 2.7.11.1 (Proto-Oncogene Proteins c-akt); EC 5.3.1.9 (Glucose-6-Phosphate Isomerase)
[Em] Mês de entrada:1608
[Cu] Atualização por classe:161125
[Lr] Data última revisão:
161125
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:151014
[St] Status:MEDLINE
[do] DOI:10.1038/srep15101



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