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[PMID]:29217191
[Au] Autor:Yoshida K; Nakai A; Kaneshiro K; Hashimoto N; Suzuki K; Uchida K; Hashimoto T; Kawasaki Y; Tateishi K; Nakagawa N; Shibanuma N; Sakai Y; Hashiramoto A
[Ad] Endereço:Department of Biophysics, Kobe University Graduate School of Health Sciences, Kobe 654-0142, Japan.
[Ti] Título:TNF-α induces expression of the circadian clock gene Bmal1 via dual calcium-dependent pathways in rheumatoid synovial cells.
[So] Source:Biochem Biophys Res Commun;495(2):1675-1680, 2018 01 08.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Tumor necrosis factor (TNF)-α is responsible for expressions of several clock genes and affects joint symptoms of rheumatoid arthritis (RA) with diurnal fluctuation. We tried to determine the mechanism involved in over-expression of Bmal1, induced by TNF-α, in primary cultured rheumatoid synovial cells. Cells were incubated with intra-cellular Ca chelator BAPTA-AM, calcineurin inhibitor FK506 and p300/CBP (CREB binding protein) inhibitor C646, respectively, or transfected with p300 and CBP small interfering RNA (siRNA) before stimulation with TNF-α. Oscillation phase and amplitude of Bmal1, transcriptional activator Rorα, transcriptional repressor Rev-erbα, and histone acetyltransferases (p300 and Cbp) were evaluated by quantitative real-time PCR. As results, TNF-α did not influence the oscillation phase of Rev-erbα, while enhanced those of Rorα, resulting in over-expression of Bmal1. When Ca influx was inhibited by BAPTA-AM, TNF-α-mediated up-regulation of Rorα was cancelled, however, that of Bmal1 was still apparent. When we further explored another pathway between TNF-α and Bmal1, TNF-α suppressed the expression of Rev-erbα in the absence of Ca influx, as well as those of p300 and Cbp genes. Finally, actions of TNF-α, in increasing Bmal1/Rorα and decreasing Rev-erbα, were cancelled by C646 treatment or silencing of both p300 and Cbp. In conclusion, we determined a novel role of TNF-α in inducing Bmal1 via dual calcium dependent pathways; Rorα was up-regulated in the presence of Ca influx and Rev-erbα was down-regulated in the absence of that. Results proposed that inhibition of p300/CBP could be new therapeutic targets for RA.
[Mh] Termos MeSH primário: Fatores de Transcrição ARNTL/genética
Artrite Reumatoide/genética
Artrite Reumatoide/metabolismo
Sinalização do Cálcio
Relógios Circadianos/genética
Membrana Sinovial/metabolismo
Fator de Necrose Tumoral alfa/metabolismo
[Mh] Termos MeSH secundário: Artrite Reumatoide/patologia
Benzoatos/farmacologia
Proteína de Ligação a CREB/antagonistas & inibidores
Proteína de Ligação a CREB/genética
Quelantes de Cálcio/farmacologia
Sinalização do Cálcio/efeitos dos fármacos
Células Cultivadas
Proteína p300 Associada a E1A/antagonistas & inibidores
Proteína p300 Associada a E1A/genética
Ácido Egtázico/análogos & derivados
Ácido Egtázico/farmacologia
Expressão Gênica/efeitos dos fármacos
Seres Humanos
Membro 1 do Grupo D da Subfamília 1 de Receptores Nucleares/genética
Membro 1 do Grupo F da Subfamília 1 de Receptores Nucleares/genética
Pirazóis/farmacologia
RNA Mensageiro/genética
RNA Mensageiro/metabolismo
RNA Interferente Pequeno/genética
Membrana Sinovial/efeitos dos fármacos
Membrana Sinovial/patologia
Fator de Necrose Tumoral alfa/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (ARNTL Transcription Factors); 0 (ARNTL protein, human); 0 (Benzoates); 0 (C646 compound); 0 (Calcium Chelating Agents); 0 (NR1D1 protein, human); 0 (Nuclear Receptor Subfamily 1, Group D, Member 1); 0 (Nuclear Receptor Subfamily 1, Group F, Member 1); 0 (Pyrazoles); 0 (RNA, Messenger); 0 (RNA, Small Interfering); 0 (RORA protein, human); 0 (Tumor Necrosis Factor-alpha); 139890-68-9 (1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester); 526U7A2651 (Egtazic Acid); EC 2.3.1.48 (CREB-Binding Protein); EC 2.3.1.48 (CREBBP protein, human); EC 2.3.1.48 (E1A-Associated p300 Protein); EC 2.3.1.48 (EP300 protein, human)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180220
[Lr] Data última revisão:
180220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171209
[St] Status:MEDLINE


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[PMID]:28743992
[Au] Autor:Cao J; Peng J; An H; He Q; Boronina T; Guo S; White MF; Cole PA; He L
[Ad] Endereço:Division of Metabolism, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
[Ti] Título:Endotoxemia-mediated activation of acetyltransferase P300 impairs insulin signaling in obesity.
[So] Source:Nat Commun;8(1):131, 2017 07 25.
[Is] ISSN:2041-1723
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Diabetes and obesity are characterized by insulin resistance and chronic low-grade inflammation. An elevated plasma concentration of lipopolysaccharide (LPS) caused by increased intestinal permeability during diet-induced obesity promotes insulin resistance in mice. Here, we show that LPS induces endoplasmic reticulum (ER) stress and protein levels of P300, an acetyltransferase involved in glucose production. In high-fat diet fed and genetically obese ob/ob mice, P300 translocates from the nucleus into the cytoplasm of hepatocytes. We also demonstrate that LPS activates the transcription factor XBP1 via the ER stress sensor IRE1, resulting in the induction of P300 which, in turn, acetylates IRS1/2, inhibits its association with the insulin receptor, and disrupts insulin signaling. Pharmacological inhibition of P300 acetyltransferase activity by a specific inhibitor improves insulin sensitivity and decreases hyperglycemia in obese mice. We suggest that P300 acetyltransferase activity may be a promising therapeutic target for the treatment of obese patients.Elevated plasma LPS levels have been associated with insulin resistance. Here Cao et al. show that LPS induces ER stress and P300 activity via the XBP1/IRE1 pathway. P300 acetylates IRS1/2 and inhibits its binding with the insulin receptor. The consequent impairment of insulin signaling can be rescued by pharmacological inhibition of P300.
[Mh] Termos MeSH primário: Proteína p300 Associada a E1A/metabolismo
Endotoxemia/metabolismo
Insulina/metabolismo
Obesidade/metabolismo
Transdução de Sinais
[Mh] Termos MeSH secundário: Animais
Linhagem Celular Tumoral
Proteína p300 Associada a E1A/genética
Estresse do Retículo Endoplasmático/efeitos dos fármacos
Estresse do Retículo Endoplasmático/genética
Perfilação da Expressão Gênica/métodos
Immunoblotting
Resistência à Insulina
Lipopolissacarídeos/farmacologia
Fígado/efeitos dos fármacos
Fígado/metabolismo
Masculino
Proteínas de Membrana/genética
Proteínas de Membrana/metabolismo
Camundongos Endogâmicos C57BL
Camundongos Obesos
Obesidade/genética
Proteínas Serina-Treonina Quinases/genética
Proteínas Serina-Treonina Quinases/metabolismo
Receptor de Insulina/genética
Receptor de Insulina/metabolismo
Proteína 1 de Ligação a X-Box/genética
Proteína 1 de Ligação a X-Box/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Insulin); 0 (Lipopolysaccharides); 0 (Membrane Proteins); 0 (X-Box Binding Protein 1); 0 (Xbp1 protein, mouse); EC 2.3.1.48 (E1A-Associated p300 Protein); EC 2.7.1.- (Ern2 protein, mouse); EC 2.7.10.1 (Receptor, Insulin); EC 2.7.11.1 (Protein-Serine-Threonine Kinases)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:180217
[Lr] Data última revisão:
180217
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170727
[St] Status:MEDLINE
[do] DOI:10.1038/s41467-017-00163-w


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[PMID]:29053796
[Au] Autor:Nibbeling EAR; Duarri A; Verschuuren-Bemelmans CC; Fokkens MR; Karjalainen JM; Smeets CJLM; de Boer-Bergsma JJ; van der Vries G; Dooijes D; Bampi GB; van Diemen C; Brunt E; Ippel E; Kremer B; Vlak M; Adir N; Wijmenga C; van de Warrenburg BPC; Franke L; Sinke RJ; Verbeek DS
[Ad] Endereço:Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
[Ti] Título:Exome sequencing and network analysis identifies shared mechanisms underlying spinocerebellar ataxia.
[So] Source:Brain;140(11):2860-2878, 2017 Nov 01.
[Is] ISSN:1460-2156
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The autosomal dominant cerebellar ataxias, referred to as spinocerebellar ataxias in genetic nomenclature, are a rare group of progressive neurodegenerative disorders characterized by loss of balance and coordination. Despite the identification of numerous disease genes, a substantial number of cases still remain without a genetic diagnosis. Here, we report five novel spinocerebellar ataxia genes, FAT2, PLD3, KIF26B, EP300, and FAT1, identified through a combination of exome sequencing in genetically undiagnosed families and targeted resequencing of exome candidates in a cohort of singletons. We validated almost all genes genetically, assessed damaging effects of the gene variants in cell models and further consolidated a role for several of these genes in the aetiology of spinocerebellar ataxia through network analysis. Our work links spinocerebellar ataxia to alterations in synaptic transmission and transcription regulation, and identifies these as the main shared mechanisms underlying the genetically diverse spinocerebellar ataxia types.
[Mh] Termos MeSH primário: Redes Reguladoras de Genes/genética
Ataxias Espinocerebelares/genética
[Mh] Termos MeSH secundário: Animais
Células COS
Caderinas/genética
Cercopithecus aethiops
Proteína p300 Associada a E1A/genética
Exoma/genética
Feminino
Células HEK293
Seres Humanos
Cinesina/genética
Masculino
Linhagem
Fosfolipase D/genética
Plasmídeos
Reação em Cadeia da Polimerase em Tempo Real
Reação em Cadeia da Polimerase Via Transcriptase Reversa
Análise de Sequência de DNA
Transfecção
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cadherins); 0 (FAT1 protein, human); 0 (FAT2 protein, human); EC 2.3.1.48 (E1A-Associated p300 Protein); EC 2.3.1.48 (EP300 protein, human); EC 3.1.4.4 (Phospholipase D); EC 3.1.4.4 (phospholipase D3, human); EC 3.6.1.- (KIF26B protein, human); EC 3.6.4.4 (Kinesin)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171107
[Lr] Data última revisão:
171107
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:171021
[St] Status:MEDLINE
[do] DOI:10.1093/brain/awx251


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[PMID]:28887413
[Au] Autor:Murakami S; Nagari A; Kraus WL
[Ad] Endereço:The Laboratory of Signaling and Gene Expression, Cecil H. and Ida Green Center for Reproductive Biology Sciences, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
[Ti] Título:Dynamic assembly and activation of estrogen receptor α enhancers through coregulator switching.
[So] Source:Genes Dev;31(15):1535-1548, 2017 Aug 01.
[Is] ISSN:1549-5477
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Although many features of active transcriptional enhancers have been defined by genomic assays, we lack a clear understanding of the order of events leading to enhancer formation and activation as well as the dynamics of coregulator interactions within the enhancer complex. Here, we used selective loss- or gain-of-function mutants of estrogen receptor α (ERα) to define two distinct phases of ligand-dependent enhancer formation. In the first phase (0-20 min), p300 is recruited to ERα by Mediator as well as p300's acetylhistone-binding bromodomain to promote initial enhancer formation, which is not competent for sustained activation. In the second phase (20-45 min), p300 is recruited to ERα by steroid receptor coregulators (SRCs) for enhancer maturation and maintenance. Successful transition between these two phases ("coregulator switching") is required for proper enhancer function. Failure to recruit p300 during either phase leads to abortive enhancer formation and a lack of target gene expression. Our results reveal an ordered and cooperative assembly of ERα enhancers requiring functional interplay among p300, Mediator, and SRCs, which has implications for hormone-dependent gene regulation in breast cancers. More broadly, our results demonstrate the unexpectedly dynamic nature of coregulator interactions within enhancer complexes, which are likely to be a defining feature of all enhancers.
[Mh] Termos MeSH primário: Neoplasias da Mama/genética
Proteína p300 Associada a E1A/metabolismo
Elementos Facilitadores Genéticos
Receptor alfa de Estrogênio/genética
Estrogênios/metabolismo
Coativador 2 de Receptor Nuclear/metabolismo
Coativador 3 de Receptor Nuclear/metabolismo
[Mh] Termos MeSH secundário: Cromatina/metabolismo
Proteína p300 Associada a E1A/genética
Estradiol/metabolismo
Feminino
Regulação Neoplásica da Expressão Gênica
Seres Humanos
Estimativa de Kaplan-Meier
Células MCF-7
Complexo Mediador/metabolismo
Proteínas Nucleares/metabolismo
Coativador 2 de Receptor Nuclear/genética
Coativador 3 de Receptor Nuclear/genética
Estatísticas não Paramétricas
Transcrição Genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Chromatin); 0 (Estrogen Receptor alpha); 0 (Estrogens); 0 (Mediator Complex); 0 (Nuclear Proteins); 0 (Nuclear Receptor Coactivator 2); 0 (estrogen receptor alpha, human); 4TI98Z838E (Estradiol); EC 2.3.1.48 (E1A-Associated p300 Protein); EC 2.3.1.48 (EP300 protein, human); EC 2.3.1.48 (NCOA3 protein, human); EC 2.3.1.48 (Nuclear Receptor Coactivator 3)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171027
[Lr] Data última revisão:
171027
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170910
[St] Status:MEDLINE
[do] DOI:10.1101/gad.302182.117


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[PMID]:28844863
[Au] Autor:Yi P; Wang Z; Feng Q; Chou CK; Pintilie GD; Shen H; Foulds CE; Fan G; Serysheva I; Ludtke SJ; Schmid MF; Hung MC; Chiu W; O'Malley BW
[Ad] Endereço:Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
[Ti] Título:Structural and Functional Impacts of ER Coactivator Sequential Recruitment.
[So] Source:Mol Cell;67(5):733-743.e4, 2017 Sep 07.
[Is] ISSN:1097-4164
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Nuclear receptors recruit multiple coactivators sequentially to activate transcription. This "ordered" recruitment allows different coactivator activities to engage the nuclear receptor complex at different steps of transcription. Estrogen receptor (ER) recruits steroid receptor coactivator-3 (SRC-3) primary coactivator and secondary coactivators, p300/CBP and CARM1. CARM1 recruitment lags behind the binding of SRC-3 and p300 to ER. Combining cryo-electron microscopy (cryo-EM) structure analysis and biochemical approaches, we demonstrate that there is a close crosstalk between early- and late-recruited coactivators. The sequential recruitment of CARM1 not only adds a protein arginine methyltransferase activity to the ER-coactivator complex, it also alters the structural organization of the pre-existing ERE/ERα/SRC-3/p300 complex. It induces a p300 conformational change and significantly increases p300 HAT activity on histone H3K18 residues, which, in turn, promotes CARM1 methylation activity on H3R17 residues to enhance transcriptional activity. This study reveals a structural role for a coactivator sequential recruitment and biochemical process in ER-mediated transcription.
[Mh] Termos MeSH primário: Proteínas Adaptadoras de Sinalização CARD/metabolismo
Proteína p300 Associada a E1A/metabolismo
Receptor alfa de Estrogênio/metabolismo
Guanilato Ciclase/metabolismo
Coativador 3 de Receptor Nuclear/metabolismo
Transcrição Genética
[Mh] Termos MeSH secundário: Acetilação
Sítios de Ligação
Proteínas Adaptadoras de Sinalização CARD/química
Proteínas Adaptadoras de Sinalização CARD/genética
Microscopia Crioeletrônica
Proteínas de Ligação a DNA/genética
Proteínas de Ligação a DNA/metabolismo
Proteína p300 Associada a E1A/química
Proteína p300 Associada a E1A/genética
Receptor alfa de Estrogênio/química
Receptor alfa de Estrogênio/genética
Guanilato Ciclase/química
Guanilato Ciclase/genética
Células HEK293
Células HeLa
Histonas/química
Histonas/metabolismo
Seres Humanos
Células MCF-7
Metilação
Modelos Moleculares
Complexos Multiproteicos
Proteínas de Neoplasias/genética
Proteínas de Neoplasias/metabolismo
Coativador 3 de Receptor Nuclear/química
Coativador 3 de Receptor Nuclear/genética
Regiões Promotoras Genéticas
Ligação Proteica
Domínios e Motivos de Interação entre Proteínas
Relação Estrutura-Atividade
Fatores de Tempo
Fatores de Transcrição
Ativação Transcricional
Transfecção
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (CARD Signaling Adaptor Proteins); 0 (DNA-Binding Proteins); 0 (Estrogen Receptor alpha); 0 (GREB1 protein, human); 0 (Histones); 0 (Multiprotein Complexes); 0 (Neoplasm Proteins); 0 (TTF1 protein, human); 0 (Transcription Factors); 0 (estrogen receptor alpha, human); EC 2.3.1.48 (E1A-Associated p300 Protein); EC 2.3.1.48 (EP300 protein, human); EC 2.3.1.48 (NCOA3 protein, human); EC 2.3.1.48 (Nuclear Receptor Coactivator 3); EC 4.6.1.2 (CARD11 protein, human); EC 4.6.1.2 (Guanylate Cyclase)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170829
[St] Status:MEDLINE


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[PMID]:28819026
[Au] Autor:Jin L; Garcia J; Chan E; de la Cruz C; Segal E; Merchant M; Kharbanda S; Raisner R; Haverty PM; Modrusan Z; Ly J; Choo E; Kaufman S; Beresini MH; Romero FA; Magnuson S; Gascoigne KE
[Ad] Endereço:Department of Discovery Oncology, Genentech, Inc., South San Francisco, California.
[Ti] Título:Therapeutic Targeting of the CBP/p300 Bromodomain Blocks the Growth of Castration-Resistant Prostate Cancer.
[So] Source:Cancer Res;77(20):5564-5575, 2017 Oct 15.
[Is] ISSN:1538-7445
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Resistance invariably develops to antiandrogen therapies used to treat newly diagnosed prostate cancers, but effective treatments for castration-resistant disease remain elusive. Here, we report that the transcriptional coactivator CBP/p300 is required to maintain the growth of castration-resistant prostate cancer. To exploit this vulnerability, we developed a novel small-molecule inhibitor of the CBP/p300 bromodomain that blocks prostate cancer growth and Molecular dissection of the consequences of drug treatment revealed a critical role for CBP/p300 in histone acetylation required for the transcriptional activity of the androgen receptor and its target gene expression. Our findings offer a preclinical proof of concept for small-molecule therapies to target the CBP/p300 bromodomain as a strategy to treat castration-resistant prostate cancer. .
[Mh] Termos MeSH primário: Proteína p300 Associada a E1A/antagonistas & inibidores
Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico
Bibliotecas de Moléculas Pequenas/farmacologia
[Mh] Termos MeSH secundário: Animais
Processos de Crescimento Celular/efeitos dos fármacos
Linhagem Celular Tumoral
Proteína p300 Associada a E1A/deficiência
Proteína p300 Associada a E1A/genética
Proteína p300 Associada a E1A/metabolismo
Feminino
Expressão Gênica
Técnicas de Silenciamento de Genes
Seres Humanos
Masculino
Camundongos
Camundongos SCID
Terapia de Alvo Molecular
Neoplasias de Próstata Resistentes à Castração/genética
Neoplasias de Próstata Resistentes à Castração/metabolismo
Neoplasias de Próstata Resistentes à Castração/patologia
Domínios Proteicos
Distribuição Aleatória
Receptores Androgênicos/metabolismo
Transdução de Sinais/efeitos dos fármacos
Transfecção
Ensaios Antitumorais Modelo de Xenoenxerto
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (AR protein, human); 0 (Receptors, Androgen); 0 (Small Molecule Libraries); EC 2.3.1.48 (E1A-Associated p300 Protein); EC 2.3.1.48 (EP300 protein, human)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171106
[Lr] Data última revisão:
171106
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170819
[St] Status:MEDLINE
[do] DOI:10.1158/0008-5472.CAN-17-0314


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[PMID]:28757384
[Au] Autor:Jeon BN; Yoon JH; Han D; Kim MK; Kim Y; Choi SH; Song J; Kim KS; Kim K; Hur MW
[Ad] Endereço:Brain Korea 21 Plus Project for Medical Science, Severance Biomedical Research Institute, Department of Biochemistry and Molecular Biology, Yonsei University School of Medicine, 50-1, Yonsei-Ro, SeoDaeMoon-Ku, Seoul 03722, Republic of Korea.
[Ti] Título:ZNF509S1 downregulates PUMA by inhibiting p53K382 acetylation and p53-DNA binding.
[So] Source:Biochim Biophys Acta;1860(9):962-972, 2017 09.
[Is] ISSN:0006-3002
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Expression of the POK family protein ZNF509L, and -its S1 isoform, is induced by p53 upon exposure to genotoxic stress. Due to alternative splicing of the ZNF509 primary transcript, ZNF509S1 lacks the 6 zinc-fingers and C-terminus of ZNF509L, resulting in only one zinc-finger. ZNF509L and -S1 inhibit cell proliferation by activating p21/CDKN1A and RB transcription, respectively. When cells are exposed to severe DNA damage, p53 activates PUMA (p53-upregulated modulator of apoptosis) transcription. Interestingly, apoptosis due to transcriptional activation of PUMA by p53 is attenuated by ZNF509S1. Thus we investigated the molecular mechanism(s) underlying the transcriptional attenuation and anti-apoptotic effects of ZNF509S1. We show that ZNF509S1 modulation of p53 activity is important in PUMA gene transcription by modulating post-translational modification of p53 by p300. ZNF509S1 directly interacts with p53 and inhibits p300-mediated acetylation of p53 lysine K382, with deacetylation of p53 K382 leading to decreased DNA binding at the p53 response element 1 of the PUMA promoter. ZNF509S1 may play a role not only in cell cycle arrest, by activating RB expression, but also in rescuing cells from apoptotic death by repressing PUMA expression in cells exposed to severe DNA damage.
[Mh] Termos MeSH primário: Proteínas de Ligação a DNA/metabolismo
DNA/metabolismo
Regulação para Baixo/fisiologia
Puma/metabolismo
Proteína Supressora de Tumor p53/metabolismo
[Mh] Termos MeSH secundário: Acetilação
Animais
Apoptose/fisiologia
Proteínas Reguladoras de Apoptose/metabolismo
Linhagem Celular
Linhagem Celular Tumoral
Proliferação Celular/fisiologia
Inibidor de Quinase Dependente de Ciclina p21/metabolismo
Dano ao DNA/fisiologia
Proteína p300 Associada a E1A
Células HCT116
Células HEK293
Seres Humanos
Regiões Promotoras Genéticas/fisiologia
Ligação Proteica/fisiologia
Processamento de Proteína Pós-Traducional/fisiologia
Ativação Transcricional/fisiologia
Dedos de Zinco/fisiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Apoptosis Regulatory Proteins); 0 (Cyclin-Dependent Kinase Inhibitor p21); 0 (DNA-Binding Proteins); 0 (TP53 protein, human); 0 (Tumor Suppressor Protein p53); 0 (ZNF509 protein, human); 9007-49-2 (DNA); EC 2.3.1.48 (E1A-Associated p300 Protein); EC 2.3.1.48 (EP300 protein, human)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171103
[Lr] Data última revisão:
171103
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170801
[St] Status:MEDLINE


  8 / 960 MEDLINE  
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[PMID]:28732206
[Au] Autor:Wang SP; Tang Z; Chen CW; Shimada M; Koche RP; Wang LH; Nakadai T; Chramiec A; Krivtsov AV; Armstrong SA; Roeder RG
[Ad] Endereço:Laboratory of Biochemistry and Molecular Biology, The Rockefeller University, New York, NY 10065, USA.
[Ti] Título:A UTX-MLL4-p300 Transcriptional Regulatory Network Coordinately Shapes Active Enhancer Landscapes for Eliciting Transcription.
[So] Source:Mol Cell;67(2):308-321.e6, 2017 Jul 20.
[Is] ISSN:1097-4164
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Enhancer activation is a critical step for gene activation. Here we report an epigenetic crosstalk at enhancers between the UTX (H3K27 demethylase)-MLL4 (H3K4 methyltransferase) complex and the histone acetyltransferase p300. We demonstrate that UTX, in a demethylase activity-independent manner, facilitates conversion of inactive enhancers in embryonic stem cells to an active (H3K4me1 /H3K27ac ) state by recruiting and coupling the enzymatic functions of MLL4 and p300. Loss of UTX leads to attenuated enhancer activity, characterized by reduced levels of H3K4me1 and H3K27ac as well as impaired transcription. The UTX-MLL4 complex enhances p300-dependent H3K27 acetylation through UTX-dependent stimulation of p300 recruitment, while MLL4-mediated H3K4 monomethylation, reciprocally, requires p300 function. Importantly, MLL4-generated H3K4me1 further enhances p300-dependent transcription. This work reveals a previously unrecognized cooperativity among enhancer-associated chromatin modulators, including a unique function for UTX, in establishing an "active enhancer landscape" and defines a detailed mechanism for the joint deposition of H3K4me1 and H3K27ac.
[Mh] Termos MeSH primário: Cromatina/metabolismo
Proteína p300 Associada a E1A/metabolismo
Células-Tronco Embrionárias/enzimologia
Elementos Facilitadores Genéticos
Histona Desmetilases/metabolismo
Histona-Lisina N-Metiltransferase/metabolismo
Transcrição Genética
Ativação Transcricional
[Mh] Termos MeSH secundário: Animais
Cromatina/genética
Montagem e Desmontagem da Cromatina
Proteína p300 Associada a E1A/genética
Retroalimentação Fisiológica
Redes Reguladoras de Genes
Células HEK293
Histona Desmetilases/genética
Histona-Lisina N-Metiltransferase/genética
Histonas/metabolismo
Seres Humanos
Masculino
Metilação
Camundongos
Interferência de RNA
Transfecção
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Chromatin); 0 (Histones); EC 1.14.11.- (Histone Demethylases); EC 1.14.11.- (Utx protein, mouse); EC 2.1.1.43 (Histone-Lysine N-Methyltransferase); EC 2.1.1.43 (MLL4 protein, mouse); EC 2.3.1.48 (E1A-Associated p300 Protein); EC 2.3.1.48 (Ep300 protein, mouse)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170926
[Lr] Data última revisão:
170926
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170722
[St] Status:MEDLINE


  9 / 960 MEDLINE  
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[PMID]:28625977
[Au] Autor:Jin K; Zhou W; Han X; Wang Z; Li B; Jeffries S; Tao W; Robbins DJ; Capobianco AJ
[Ad] Endereço:Molecular Oncology Program, Division of Surgical Oncology, Dewitt Daughtry Family Department of Surgery, Miller School of Medicine, University of Miami, Miami, Florida.
[Ti] Título:Acetylation of Mastermind-like 1 by p300 Drives the Recruitment of NACK to Initiate Notch-Dependent Transcription.
[So] Source:Cancer Res;77(16):4228-4237, 2017 Aug 15.
[Is] ISSN:1538-7445
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Although it has long been appreciated that p300 acts as a critical Notch coactivator, the mechanistic details of p300 in Notch-mediated transcription remain unclear. We previously demonstrated that PEAK1-related kinase activating pseudokinase 1 (NACK), also known as SGK223, is a critical coactivator of Notch signaling and binds to the Notch1 ternary complex. Herein we report that p300 and CBP acetylate Mastermind-like 1 (Maml1) on amino acid residues K188 and K189 to recruit NACK to the Notch1 ternary complex, which results in the recruitment of RNA polymerase II to initiate transcription. NACK is recruited to the ternary complexes containing Maml1 and Maml3, but not Maml2. Simultaneous inhibition of p300/CBP and Notch has a synergistic effect in esophageal adenocarcinoma. In summary, this study provides a deeper mechanistic understanding of the assembly of the Notch transcriptional complex and provides rationale and proof of concept for a combinatorial therapeutic attack on Notch-dependent cancers. .
[Mh] Termos MeSH primário: Proteínas de Ligação a DNA/metabolismo
Proteína p300 Associada a E1A/metabolismo
Receptor Notch1/metabolismo
Fatores de Transcrição/metabolismo
[Mh] Termos MeSH secundário: Acetilação
Animais
Linhagem Celular Tumoral
Expressão Gênica
Células HEK293
Xenoenxertos
Seres Humanos
Camundongos
RNA Polimerase II/metabolismo
Receptor Notch1/genética
Transdução de Sinais
Transcrição Genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (DNA-Binding Proteins); 0 (MAML1 protein, human); 0 (NOTCH1 protein, human); 0 (Receptor, Notch1); 0 (Transcription Factors); EC 2.3.1.48 (E1A-Associated p300 Protein); EC 2.3.1.48 (EP300 protein, human); EC 2.7.7.- (RNA Polymerase II)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170929
[Lr] Data última revisão:
170929
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170620
[St] Status:MEDLINE
[do] DOI:10.1158/0008-5472.CAN-16-3156


  10 / 960 MEDLINE  
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[PMID]:28551630
[Au] Autor:Godlewski J; Krazinski BE; Kowalczyk AE; Kiewisz J; Kiezun J; Kwiatkowski P; Sliwinska-Jewsiewicka A; Wierzbicki PW; Kmiec Z
[Ad] Endereço:Department of Human Histology and Embryology, Faculty of Medical Sciences, University of Warmia and Mazury in Olsztyn, Olsztyn, Poland janusz350@poczta.onet.pl.
[Ti] Título:Expression and Prognostic Significance of , and in Clear Cell Renal Cell Carcinoma.
[So] Source:Anticancer Res;37(6):2927-2937, 2017 06.
[Is] ISSN:1791-7530
[Cp] País de publicação:Greece
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Histone acetyltransferase E1A-binding protein p300 (EP300), tumor protein p53 (TP53) and B-cell lymphoma-2-associated X protein (BAX) contribute to the regulation of the cell cycle and apoptosis, cellular processes that are often impaired in cancer cells. The aim of this study was to determine the expression levels of EP300, TP53 and BAX genes and their respective proteins in clear cell renal cell carcinoma (ccRCC) and evaluate the value of these factors as prognostic factors. MATERIALS AND METHODS: EP300, TP53 and BAX expression at the transcript and protein levels were determined by quantitative polymerase-chain reaction (QPCR) and immunohistochemistry (IHC) in paired tumor and kidney specimens from 31 patients with ccRCC. RESULTS: Levels of EP300, TP53 and BAX transcripts were found increased in tumor tissues. Immunoreactivity for TP53 was elevated in cancer cells when compared to unchanged kidney, while EP300 and BAX immunoexpression in ccRCC did not differ from that of normal renal tissue. Immunoreactivity for TP53 was positively associated with larger tumor size. In contrast, stronger BAX immunoexpression correlated with smaller tumor diameters. The average immunoreactivity for BAX was higher in localized, kidney-confined tumor than in advanced/recurrent tumors. None of the analyzed transcripts or proteins correlated with the overall survival of patients. CONCLUSION: Although TP53 and BAX immunoreactivity levels were associated with some clinicopathological parameters of the patients, the expression of EP300, TP53 and BAX did not reveal any prognostic significance in ccRCC.
[Mh] Termos MeSH primário: Carcinoma de Células Renais/metabolismo
Proteína p300 Associada a E1A/metabolismo
Neoplasias Renais/metabolismo
Proteína Supressora de Tumor p53/metabolismo
Proteína X Associada a bcl-2/metabolismo
[Mh] Termos MeSH secundário: Adulto
Idoso
Idoso de 80 Anos ou mais
Carcinoma de Células Renais/genética
Proteínas de Ciclo Celular/genética
Proteínas de Ciclo Celular/metabolismo
Proteína p300 Associada a E1A/genética
Feminino
Seres Humanos
Rim/metabolismo
Neoplasias Renais/genética
Masculino
Meia-Idade
Prognóstico
Fatores de Transcrição/genética
Fatores de Transcrição/metabolismo
Proteína Supressora de Tumor p53/genética
Proteínas Supressoras de Tumor/genética
Proteínas Supressoras de Tumor/metabolismo
Proteína X Associada a bcl-2/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (BAX protein, human); 0 (Cell Cycle Proteins); 0 (PLAGL1 protein, human); 0 (TP53 protein, human); 0 (Transcription Factors); 0 (Tumor Suppressor Protein p53); 0 (Tumor Suppressor Proteins); 0 (bcl-2-Associated X Protein); EC 2.3.1.48 (E1A-Associated p300 Protein); EC 2.3.1.48 (EP300 protein, human)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170821
[Lr] Data última revisão:
170821
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170529
[St] Status:MEDLINE



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