Base de dados : MEDLINE
Pesquisa : G02.111.540 [Categoria DeCS]
Referências encontradas : 728 [refinar]
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[PMID]:29362370
[Au] Autor:Kathayat RS; Cao Y; Elvira PD; Sandoz PA; Zaballa ME; Springer MZ; Drake LE; Macleod KF; van der Goot FG; Dickinson BC
[Ad] Endereço:Department of Chemistry, The University of Chicago, Chicago, IL, 60637, USA.
[Ti] Título:Active and dynamic mitochondrial S-depalmitoylation revealed by targeted fluorescent probes.
[So] Source:Nat Commun;9(1):334, 2018 01 23.
[Is] ISSN:2041-1723
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The reversible modification of cysteine residues by thioester formation with palmitate (S-palmitoylation) is an abundant lipid post-translational modification (PTM) in mammalian systems. S-palmitoylation has been observed on mitochondrial proteins, providing an intriguing potential connection between metabolic lipids and mitochondrial regulation. However, it is unknown whether and/or how mitochondrial S-palmitoylation is regulated. Here we report the development of mitoDPPs, targeted fluorescent probes that measure the activity levels of "erasers" of S-palmitoylation, acyl-protein thioesterases (APTs), within mitochondria of live cells. Using mitoDPPs, we discover active S-depalmitoylation in mitochondria, in part mediated by APT1, an S-depalmitoylase previously thought to reside in the cytosol and on the Golgi apparatus. We also find that perturbation of long-chain acyl-CoA cytoplasm and mitochondrial regulatory proteins, respectively, results in selective responses from cytosolic and mitochondrial S-depalmitoylases. Altogether, this work reveals that mitochondrial S-palmitoylation is actively regulated by "eraser" enzymes that respond to alterations in mitochondrial lipid homeostasis.
[Mh] Termos MeSH primário: Corantes Fluorescentes/metabolismo
Mitocôndrias/metabolismo
Dinâmica Mitocondrial
Tioléster Hidrolases/metabolismo
[Mh] Termos MeSH secundário: Células A549
Acil Coenzima A/metabolismo
Células HEK293
Células HeLa
Seres Humanos
Cinética
Lipoilação
Células MCF-7
Microscopia Confocal
Interferência de RNA
Tioléster Hidrolases/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Acyl Coenzyme A); 0 (Fluorescent Dyes); EC 3.1.2.- (LYPLA1 protein, human); EC 3.1.2.- (Thiolester Hydrolases)
[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:180125
[St] Status:MEDLINE
[do] DOI:10.1038/s41467-017-02655-1


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[PMID]:29287726
[Au] Autor:Kim Y; Yang H; Min JK; Park YJ; Jeong SH; Jang SW; Shim S
[Ad] Endereço:Department of Biochemistry, Chungbuk National University, Cheongju, Republic of Korea.
[Ti] Título:CCN3 secretion is regulated by palmitoylation via ZDHHC22.
[So] Source:Biochem Biophys Res Commun;495(4):2573-2578, 2018 01 22.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Normal extracellular secretion of nephroblastoma overexpressed (NOV, also known as CCN3) is important for the adhesion, migration, and differentiation of cells. In previous studies, we have shown that the intracellular accumulation of CCN3 inhibits the growth of prominent neurons. Increased intracellular CCN3 can be induced through various processes, such as transcription, detoxification, and posttranslational modification. In general, posttranslational modifications are very important for protein secretion. However, it is unclear whether posttranslational modification is necessary for CCN3 secretion. In this study, we have conducted mutational analysis of CCN3 to demonstrate that its thrombospondin type-1 (TSP1) domain is important for CCN3 secretion and intracellular function. Point mutation analysis confirmed that CCN3 secretion was inhibited by cysteine (C)241 mutation, and overexpression of CCN3-C241A inhibited neuronal axonal growth in vivo. Furthermore, we demonstrated that palmitoylation is important for the extracellular secretion of CCN3 and that zinc finger DHHC-type containing 22 (ZDHHC22), a palmityoltransferase, can interact with CCN3. Taken together, our results suggest that palmitoylation by ZDHHC22 at C241 in the CCN3 TSP1 domain may be required for the secretion of CCN3. Aberrant palmitoylation induces intracellular accumulation of CCN3, inhibiting neuronal axon growth.
[Mh] Termos MeSH primário: Carnitina O-Palmitoiltransferase/química
Carnitina O-Palmitoiltransferase/metabolismo
Lipoilação/fisiologia
Proteínas de Membrana/química
Proteínas de Membrana/metabolismo
Proteína Sobre-Expressa em Nefroblastoma/química
Proteína Sobre-Expressa em Nefroblastoma/metabolismo
Neurônios/metabolismo
[Mh] Termos MeSH secundário: Animais
Sítios de Ligação
Células HEK293
Seres Humanos
Camundongos
Camundongos Endogâmicos ICR
Neurônios/química
Neurônios/citologia
Ligação Proteica
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE; PATIENT EDUCATION HANDOUT; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Membrane Proteins); 0 (NOV protein, human); 0 (Nephroblastoma Overexpressed Protein); EC 2.3.1.- (ZDHHC22 protein, human); EC 2.3.1.21 (Carnitine O-Palmitoyltransferase)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180222
[Lr] Data última revisão:
180222
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171231
[St] Status:MEDLINE


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[PMID]:29326245
[Au] Autor:Rana MS; Kumar P; Lee CJ; Verardi R; Rajashankar KR; Banerjee A
[Ad] Endereço:Cell Biology and Neurobiology Branch, National Institutes of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
[Ti] Título:Fatty acyl recognition and transfer by an integral membrane -acyltransferase.
[So] Source:Science;359(6372), 2018 01 12.
[Is] ISSN:1095-9203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:DHHC (Asp-His-His-Cys) palmitoyltransferases are eukaryotic integral membrane enzymes that catalyze protein palmitoylation, which is important in a range of physiological processes, including small guanosine triphosphatase (GTPase) signaling, cell adhesion, and neuronal receptor scaffolding. We present crystal structures of two DHHC palmitoyltransferases and a covalent intermediate mimic. The active site resides at the membrane-cytosol interface, which allows the enzyme to catalyze thioester-exchange chemistry by using fatty acyl-coenzyme A and explains why membrane-proximal cysteines are candidates for palmitoylation. The acyl chain binds in a cavity formed by the transmembrane domain. We propose a mechanism for acyl chain-length selectivity in DHHC enzymes on the basis of cavity mutants with preferences for shorter and longer acyl chains.
[Mh] Termos MeSH primário: Acil Coenzima A/metabolismo
Aciltransferases/química
Proteínas de Peixe-Zebra/química
[Mh] Termos MeSH secundário: Aciltransferases/genética
Aciltransferases/metabolismo
Animais
Domínio Catalítico
Cristalização
Cristalografia por Raios X
Cisteína/química
Seres Humanos
Lipoilação
Modelos Moleculares
Mutação
Domínios Proteicos
Estrutura Secundária de Proteína
Especificidade por Substrato
Proteínas de Peixe-Zebra/genética
Proteínas de Peixe-Zebra/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, N.I.H., INTRAMURAL; RESEARCH SUPPORT, U.S. GOV'T, NON-P.H.S.
[Nm] Nome de substância:
0 (Acyl Coenzyme A); 0 (Zebrafish Proteins); EC 2.3.- (Acyltransferases); EC 2.3.- (ZDHHC20 protein, human); K848JZ4886 (Cysteine)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180207
[Lr] Data última revisão:
180207
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180113
[St] Status:MEDLINE


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[PMID]:28747438
[Au] Autor:Seno K; Hayashi F
[Ad] Endereço:From the Department of Biology, Faculty of Medicine, and.
[Ti] Título:Palmitoylation is a prerequisite for dimerization-dependent raftophilicity of rhodopsin.
[So] Source:J Biol Chem;292(37):15321-15328, 2017 09 15.
[Is] ISSN:1083-351X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The visual photopigment rhodopsin (Rh) is a prototypical G protein-coupled receptor (GPCR) responsible for initiation of the phototransduction cascade in rod photoreceptors. Similar to other GPCRs, Rh can form dimers or even higher oligomers and tends to have a supramolecular organization that is likely important in the dim light response. Rh also exhibits high affinity for lipid rafts ( raftophilicity) upon light-dependent binding with the cognate G protein transducin (G ), suggesting the presence of lipid raft-like domains in the retinal disk membrane and their importance in phototransduction. However, the relationship between Rh oligomerization and lipid rafts in the disk membrane remains to be explored. Given previous findings that G binds to dimeric Rh and that Rh is posttranslationally modified with two highly raftophilic palmitoyl moieties, we hypothesized that Rh becomes raftophilic upon dimerization. Here, using biochemical assays, we found that Rh*-G complexes in the detergent-resistant membrane are partially resistant to cholesterol depletion by methyl-ß-cyclodextrin and that the Rh-to-G stoichiometry in this methyl-ß-cyclodextrin-resistant complex is 2:1. Next, we found that IgG-mediated Rh-Rh cross-linking renders Rh highly raftophilic, supporting the premise that Rh becomes raftophilic upon dimerization. Rh depalmitoylation via reduction of thioester linkages blocked the translocation of IgG-cross-linked Rh to the detergent-resistant membrane, highlighting that the two palmitoyl moieties are important for the dimerization-dependent raftophilicity of Rh. These results indicate that palmitoylated GPCRs such as Rh can acquire raftophilicity upon G protein-stabilized dimerization and thereby organize receptor-cluster rafts by recruiting raftophilic lipids.
[Mh] Termos MeSH primário: Lipoilação
Microdomínios da Membrana/metabolismo
Modelos Moleculares
Processamento de Proteína Pós-Traducional
Rana catesbeiana/fisiologia
Rodopsina/metabolismo
Segmento Externo da Célula Bastonete/metabolismo
[Mh] Termos MeSH secundário: Proteínas de Anfíbios/química
Proteínas de Anfíbios/metabolismo
Animais
Anticorpos Monoclonais/metabolismo
Cisteína/química
Cistina/química
Adaptação à Escuridão
Dimerização
Interações Hidrofóbicas e Hidrofílicas
Cinética
Luz
Lipoilação/efeitos da radiação
Microdomínios da Membrana/química
Microdomínios da Membrana/efeitos da radiação
Oxirredução
Conformação Proteica/efeitos da radiação
Multimerização Proteica/efeitos da radiação
Processamento de Proteína Pós-Traducional/efeitos da radiação
Estabilidade Proteica/efeitos da radiação
Rodopsina/química
Segmento Externo da Célula Bastonete/química
Segmento Externo da Célula Bastonete/efeitos da radiação
Transducina/química
Transducina/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Amphibian Proteins); 0 (Antibodies, Monoclonal); 48TCX9A1VT (Cystine); 9009-81-8 (Rhodopsin); EC 3.6.5.1 (Transducin); K848JZ4886 (Cysteine)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171230
[Lr] Data última revisão:
171230
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170728
[St] Status:MEDLINE
[do] DOI:10.1074/jbc.M117.804880


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[PMID]:28899783
[Au] Autor:Kharbanda A; Runkle K; Wang W; Witze ES
[Ad] Endereço:Department of Cancer Biology, University of Pennsylvania, Philadelphia, PA 19104, United States; Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, United States.
[Ti] Título:Induced sensitivity to EGFR inhibitors is mediated by palmitoylated cysteine 1025 of EGFR and requires oncogenic Kras.
[So] Source:Biochem Biophys Res Commun;493(1):213-219, 2017 Nov 04.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Currently, there are no effective therapeutic strategies targeting Kras driven cancers, and therefore, identifying new targeted therapies and overcoming drug resistance have become paramount for effective long-term cancer therapy. We have found that reducing expression of the palmitoyl transferase DHHC20 increases cell death induced by the EGFR inhibitor gefitinib in Kras and EGFR mutant cell lines, but not MCF7 cells harboring wildtype Kras. We show that the increased gefitinib sensitivity in cancer cells induced by DHHC20 inhibition is mediated directly through loss of palmitoylation on a previously identified cysteine residue in the C-terminal tail of EGFR. We utilized an EGFR point mutant in which the palmitoylated cysteine 1025 is mutated to alanine (EGFR ), that results in receptor activation. Expression of the EGFR mutant alone in NIH3T3 cells does not increase sensitivity to gefitinib-induced cell death. However, when EGFR is expressed in cells expressing activated Kras , EGFR inhibitor induced cell death is increased. Surprisingly, lung cancer cells harboring the EGFR inhibitor resistant mutation, T790M, become sensitive to EGFR inhibitor treatment when DHHC20 is inhibited. Finally, the small molecule, 2-bromopalmitate, which has been shown to inhibit palmitoyl transferases, acts synergistically with gefitinib to induce cell death in the gefitinib resistant cell line NCI-H1975.
[Mh] Termos MeSH primário: Cisteína/genética
Neoplasias Experimentais/fisiopatologia
Proteínas Proto-Oncogênicas p21(ras)/metabolismo
Receptor do Fator de Crescimento Epidérmico/antagonistas & inibidores
Receptor do Fator de Crescimento Epidérmico/genética
[Mh] Termos MeSH secundário: Antineoplásicos/farmacologia
Antineoplásicos/uso terapêutico
Apoptose/efeitos dos fármacos
Cocarcinogênese
Cisteína/metabolismo
Relação Dose-Resposta a Droga
Resistência a Medicamentos Antineoplásicos
Seres Humanos
Lipoilação/efeitos dos fármacos
Lipoilação/genética
Células MCF-7
Proteínas de Membrana
Mutação
Neoplasias Experimentais/tratamento farmacológico
Neoplasias Experimentais/metabolismo
Proteínas Proto-Oncogênicas p21(ras)/genética
Quinazolinas/administração & dosagem
Quinazolinas/farmacologia
Receptor do Fator de Crescimento Epidérmico/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (GODZ protein, mouse); 0 (KRAS protein, human); 0 (Membrane Proteins); 0 (Quinazolines); EC 2.7.10.1 (EGFR protein, human); EC 2.7.10.1 (Receptor, Epidermal Growth Factor); EC 3.6.5.2 (Proto-Oncogene Proteins p21(ras)); K848JZ4886 (Cysteine); S65743JHBS (gefitinib)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171023
[Lr] Data última revisão:
171023
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170914
[St] Status:MEDLINE


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[PMID]:28860190
[Au] Autor:Gamage DG; Leikina E; Quinn ME; Ratinov A; Chernomordik LV; Millay DP
[Ad] Endereço:From the Department of Molecular Cardiovascular Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229 and.
[Ti] Título:Insights into the localization and function of myomaker during myoblast fusion.
[So] Source:J Biol Chem;292(42):17272-17289, 2017 Oct 20.
[Is] ISSN:1083-351X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Multinucleated skeletal muscle fibers form through the fusion of myoblasts during development and regeneration. Previous studies identified myomaker (Tmem8c) as a muscle-specific membrane protein essential for fusion. However, the specific function of myomaker and how its function is regulated are unknown. To explore these questions, we first examined the cellular localization of endogenous myomaker. Two independent antibodies showed that whereas myomaker does localize to the plasma membrane in cultured myoblasts, the protein also resides in the Golgi and post-Golgi vesicles. These results raised questions regarding the precise cellular location of myomaker function and mechanisms that govern myomaker trafficking between these cellular compartments. Using a synchronized fusion assay, we demonstrated that myomaker functions at the plasma membrane to drive fusion. Trafficking of myomaker is regulated by palmitoylation of C-terminal cysteine residues that allows Golgi localization. Moreover, dissection of the C terminus revealed that palmitoylation was not sufficient for complete fusogenic activity suggesting a function for other amino acids within this C-terminal region. Indeed, C-terminal mutagenesis analysis highlighted the importance of a C-terminal leucine for function. These data reveal that myoblast fusion requires myomaker activity at the plasma membrane and is potentially regulated by proper myomaker trafficking.
[Mh] Termos MeSH primário: Antígenos de Diferenciação/metabolismo
Complexo de Golgi/metabolismo
Lipoilação/fisiologia
Fusão de Membrana/fisiologia
Proteínas de Membrana/metabolismo
Proteínas Musculares/metabolismo
Mioblastos Esqueléticos/metabolismo
[Mh] Termos MeSH secundário: Animais
Antígenos de Diferenciação/genética
Linhagem Celular
Complexo de Golgi/genética
Proteínas de Membrana/genética
Camundongos
Proteínas Musculares/genética
Mioblastos Esqueléticos/citologia
Domínios Proteicos
Transporte Proteico/fisiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antigens, Differentiation); 0 (Membrane Proteins); 0 (Muscle Proteins); 0 (myomaker protein, mouse)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171028
[Lr] Data última revisão:
171028
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170902
[St] Status:MEDLINE
[do] DOI:10.1074/jbc.M117.811372


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[PMID]:28848045
[Au] Autor:Roy K; Jerman S; Jozsef L; McNamara T; Onyekaba G; Sun Z; Marin EP
[Ad] Endereço:From the Department of Internal Medicine, Section of Nephrology, Yale University School of Medicine, New Haven, Connecticut 06520-8029 and.
[Ti] Título:Palmitoylation of the ciliary GTPase ARL13b is necessary for its stability and its role in cilia formation.
[So] Source:J Biol Chem;292(43):17703-17717, 2017 Oct 27.
[Is] ISSN:1083-351X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Primary cilia are hairlike extensions of the plasma membrane of most mammalian cells that serve specialized signaling functions. To traffic properly to cilia, multiple cilia proteins rely on palmitoylation, the post-translational attachment of a saturated 16-carbon lipid. However, details regarding the mechanism of how palmitoylation affects cilia protein localization and function are unknown. Herein, we investigated the protein ADP-ribosylation factor-like GTPase 13b (ARL13b) as a model palmitoylated ciliary protein. Using biochemical, cellular, and studies, we found that ARL13b palmitoylation occurs in mouse kidneys and that it is required for trafficking to and function within cilia. Myristoylation, a 14-carbon lipid, is shown to largely substitute for palmitoylation with regard to cilia localization of ARL13b, but not with regard to its function within cilia. The functional importance of palmitoylation results in part from a dramatic increase in ARL13b stability, which is not observed with myristoylation. Additional results show that blockade of depalmitoylation slows the degradation of ARL13b that occurs during cilia resorption, raising the possibility that the sensitivity of ARL13b stability to palmitoylation may be exploited by the cell to accelerate degradation of ARL13b by depalmitoylating it. Together, the results show that palmitoylation plays a unique and critical role in controlling the localization, stability, abundance, and thus function of ARL13b. Pharmacological manipulation of protein palmitoylation may be a strategy to alter cilia function.
[Mh] Termos MeSH primário: Fatores de Ribosilação do ADP/metabolismo
Lipoilação/fisiologia
[Mh] Termos MeSH secundário: Fatores de Ribosilação do ADP/genética
Animais
Cílios/enzimologia
Cílios/genética
Estabilidade Enzimática/fisiologia
Células HEK293
Seres Humanos
Camundongos
Transporte Proteico/fisiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
EC 3.6.5.2 (ADP-Ribosylation Factors); EC 3.6.5.2 (Arl13b protein, human)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171104
[Lr] Data última revisão:
171104
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170830
[St] Status:MEDLINE
[do] DOI:10.1074/jbc.M117.792937


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[PMID]:28794042
[Au] Autor:Chlanda P; Mekhedov E; Waters H; Sodt A; Schwartz C; Nair V; Blank PS; Zimmerberg J
[Ad] Endereço:Section on Integrative Biophysics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, Maryland, USA chlandap@mail.nih.gov zimmerbj@mail.nih.gov.
[Ti] Título:Palmitoylation Contributes to Membrane Curvature in Influenza A Virus Assembly and Hemagglutinin-Mediated Membrane Fusion.
[So] Source:J Virol;91(21), 2017 Nov 01.
[Is] ISSN:1098-5514
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The highly conserved cytoplasmic tail of influenza virus glycoprotein hemagglutinin (HA) contains three cysteines, posttranslationally modified by covalently bound fatty acids. While viral HA acylation is crucial in virus replication, its physico-chemical role is unknown. We used virus-like particles (VLP) to study the effect of acylation on morphology, protein incorporation, lipid composition, and membrane fusion. Deacylation interrupted HA-M1 interactions since deacylated mutant HA failed to incorporate an M1 layer within spheroidal VLP, and filamentous particles incorporated increased numbers of neuraminidase (NA). While HA acylation did not influence VLP shape, lipid composition, or HA lateral spacing, acylation significantly affected envelope curvature. Compared to wild-type HA, deacylated HA is correlated with released particles with flat envelope curvature in the absence of the matrix (M1) protein layer. The spontaneous curvature of palmitate was calculated by molecular dynamic simulations and was found to be comparable to the curvature values derived from VLP size distributions. Cell-cell fusion assays show a strain-independent failure of fusion pore enlargement among H2 (A/Japan/305/57), H3 (A/Aichi/2/68), and H3 (A/Udorn/72) viruses. In contradistinction, acylation made no difference in the low-pH-dependent fusion of isolated VLPs to liposomes: fusion pores formed and expanded, as demonstrated by the presence of complete fusion products observed using cryo-electron tomography (cryo-ET). We propose that the primary mechanism of action of acylation is to control membrane curvature and to modify HA's interaction with M1 protein, while the stunting of fusion by deacylated HA acting in isolation may be balanced by other viral proteins which help lower the energetic barrier to pore expansion. Influenza A virus is an airborne pathogen causing seasonal epidemics and occasional pandemics. Hemagglutinin (HA), a glycoprotein abundant on the virion surface, is important in both influenza A virus assembly and entry. HA is modified by acylation whose removal abrogates viral replication. Here, we used cryo-electron tomography to obtain three-dimensional images to elucidate a role for HA acylation in VLP assembly. Our data indicate that HA acylation contributes to the capability of HA to bend membranes and to HA's interaction with the M1 scaffold protein during virus assembly. Furthermore, our data on VLP and, by hypothesis, virus suggests that HA acylation, while not critical to fusion pore formation, contributes to pore expansion in a target-dependent fashion.
[Mh] Termos MeSH primário: Membrana Celular/química
Glicoproteínas de Hemaglutininação de Vírus da Influenza/metabolismo
Vírus da Influenza A/fisiologia
Lipoilação/fisiologia
Fusão de Membrana
Montagem de Vírus/fisiologia
[Mh] Termos MeSH secundário: Acilação
Animais
Membrana Celular/metabolismo
Cães
Células HEK293
Seres Humanos
Células Madin Darby de Rim Canino
Vírion/fisiologia
Replicação Viral
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Hemagglutinin Glycoproteins, Influenza Virus)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171109
[Lr] Data última revisão:
171109
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170811
[St] Status:MEDLINE


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[PMID]:28775165
[Au] Autor:Chen X; Ma H; Wang Z; Zhang S; Yang H; Fang Z
[Ad] Endereço:Anhui Province Key Laboratory of Medical Physics and Technology, Center of Medical Physics and Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, Anhui, China. xueranchen@cmpt.ac.cn z.fang@cmpt.ac.cn.
[Ti] Título:EZH2 Palmitoylation Mediated by ZDHHC5 in p53-Mutant Glioma Drives Malignant Development and Progression.
[So] Source:Cancer Res;77(18):4998-5010, 2017 Sep 15.
[Is] ISSN:1538-7445
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Gliomas with mutant p53 occurring in 30% of glioma patients exhibit therapeutic resistance and poor outcomes. In this study, we identify a novel mechanism through which mutant p53 drives cancer cell survival and malignant growth. We documented overexpression of the zinc finger protein ZDHHC5 in glioma compared with normal brain tissue and that this event tightly correlated with p53 mutations. Mechanistic investigations revealed that mutant p53 transcriptionally upregulated ZDHHC5 along with the nuclear transcription factor NF-Y. These events contributed to the development of glioma by promoting the self-renewal capacity and tumorigenicity of glioma stem-like cells, by altering the palmitoylation and phosphorylation status of the tumor suppressor EZH2. Taken together, our work highlighted ZDHHC5 as a candidate therapeutic target for management of p53-mutated gliomas. .
[Mh] Termos MeSH primário: Aciltransferases/metabolismo
Transformação Celular Neoplásica/patologia
Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo
Glioma/patologia
Mutação/genética
Recidiva Local de Neoplasia/patologia
Proteína Supressora de Tumor p53/genética
[Mh] Termos MeSH secundário: Aciltransferases/genética
Animais
Apoptose
Biomarcadores Tumorais
Neoplasias Encefálicas/genética
Neoplasias Encefálicas/metabolismo
Neoplasias Encefálicas/patologia
Ciclo Celular
Movimento Celular
Proliferação Celular
Transformação Celular Neoplásica/genética
Transformação Celular Neoplásica/metabolismo
Proteína Potenciadora do Homólogo 2 de Zeste/genética
Regulação Neoplásica da Expressão Gênica
Glioma/genética
Glioma/metabolismo
Seres Humanos
Lipoilação
Camundongos
Camundongos Nus
Invasividade Neoplásica
Recidiva Local de Neoplasia/genética
Recidiva Local de Neoplasia/metabolismo
Estadiamento de Neoplasias
Prognóstico
Taxa de Sobrevida
Células Tumorais Cultivadas
Ensaios Antitumorais Modelo de Xenoenxerto
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers, Tumor); 0 (TP53 protein, human); 0 (Tumor Suppressor Protein p53); EC 2.1.1.43 (EZH2 protein, human); EC 2.1.1.43 (Enhancer of Zeste Homolog 2 Protein); EC 2.3.- (Acyltransferases); EC 2.3.- (DHHC5 protein, human)
[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:170805
[St] Status:MEDLINE
[do] DOI:10.1158/0008-5472.CAN-17-1139


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[PMID]:28757203
[Au] Autor:Habarou F; Hamel Y; Haack TB; Feichtinger RG; Lebigot E; Marquardt I; Busiah K; Laroche C; Madrange M; Grisel C; Pontoizeau C; Eisermann M; Boutron A; Chrétien D; Chadefaux-Vekemans B; Barouki R; Bole-Feysot C; Nitschke P; Goudin N; Boddaert N; Nemazanyy I; Delahodde A; Kölker S; Rodenburg RJ; Korenke GC; Meitinger T; Strom TM; Prokisch H; Rotig A; Ottolenghi C; Mayr JA; de Lonlay P
[Ad] Endereço:Reference Center of Inherited Metabolic Diseases, University Paris Descartes, Hospital Necker Enfants Malades, APHP, 75015 Paris, France; Metabolic Biochemistry, University Paris Descartes, Hospital Necker Enfants Malades, 75015 Paris, France.
[Ti] Título:Biallelic Mutations in LIPT2 Cause a Mitochondrial Lipoylation Defect Associated with Severe Neonatal Encephalopathy.
[So] Source:Am J Hum Genet;101(2):283-290, 2017 Aug 03.
[Is] ISSN:1537-6605
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Lipoate serves as a cofactor for the glycine cleavage system (GCS) and four 2-oxoacid dehydrogenases functioning in energy metabolism (α-oxoglutarate dehydrogenase [α-KGDHc] and pyruvate dehydrogenase [PDHc]), or amino acid metabolism (branched-chain oxoacid dehydrogenase, 2-oxoadipate dehydrogenase). Mitochondrial lipoate synthesis involves three enzymatic steps catalyzed sequentially by lipoyl(octanoyl) transferase 2 (LIPT2), lipoic acid synthetase (LIAS), and lipoyltransferase 1 (LIPT1). Mutations in LIAS have been associated with nonketotic hyperglycinemia-like early-onset convulsions and encephalopathy combined with a defect in mitochondrial energy metabolism. LIPT1 deficiency spares GCS deficiency and has been associated with a biochemical signature of combined 2-oxoacid dehydrogenase deficiency leading to early death or Leigh-like encephalopathy. We report on the identification of biallelic LIPT2 mutations in three affected individuals from two families with severe neonatal encephalopathy. Brain MRI showed major cortical atrophy with white matter abnormalities and cysts. Plasma glycine was mildly increased. Affected individuals' fibroblasts showed reduced oxygen consumption rates, PDHc, α-KGDHc activities, leucine catabolic flux, and decreased protein lipoylation. A normalization of lipoylation was observed after expression of wild-type LIPT2, arguing for LIPT2 requirement in intramitochondrial lipoate synthesis. Lipoic acid supplementation did not improve clinical condition nor activities of PDHc, α-KGDHc, or leucine metabolism in fibroblasts and was ineffective in yeast deleted for the orthologous LIP2.
[Mh] Termos MeSH primário: Aciltransferases/genética
Atrofia/patologia
Encefalopatias/genética
Encéfalo/patologia
Lipoilação/genética
Mitocôndrias/metabolismo
[Mh] Termos MeSH secundário: Aminoácidos/metabolismo
Encéfalo/diagnóstico por imagem
Encefalopatias/patologia
Mapeamento Encefálico/métodos
Células Cultivadas
Metabolismo Energético/genética
Metabolismo Energético/fisiologia
Glicina/sangue
Seres Humanos
Recém-Nascido
Imagem por Ressonância Magnética
Mitocôndrias/genética
Consumo de Oxigênio/genética
Ligação Proteica/genética
Ácido Tióctico/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Amino Acids); 73Y7P0K73Y (Thioctic Acid); EC 2.3.- (Acyltransferases); EC 2.3.1.- (lipoyltransferase II); TE7660XO1C (Glycine)
[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:170801
[St] Status:MEDLINE



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