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https://www.readbyqxmd.com/read/27926504/the-immunomodulatory-effects-of-tnf-%C3%AE-inhibitors-on-human-th17-cells-via-ror%C3%AE-t-histone-acetylation
#1
Yi-Ching Lin, Yu-Chih Lin, Cheng-Chin Wu, Ming-Yii Huang, Wen-Chan Tsai, Chih-Hsing Hung, Po-Lin Kuo
The presence of interleukin (IL)-17-related cytokines correlates with rheumatoid arthritis (RA) pathogenesis. Epigenetic modifications, including histone acetylation, regulate gene expression in RA pathogenesis. Tumour necrosis factor-alpha (TNF-α) inhibitors such as etanercept and adalimumab, represent a breakthrough in RA treatment. We aimed to investigate the effects of etanercept and adalimumab on human Th17-polarized cells and the possible intracellular regulators of these effects, including the Th17-specific transcription factors signal transducer, activator of transcription 3 (STAT3), retinoid-related orphan receptor γ-T (RORγt) and epigenetic modification...
December 3, 2016: Oncotarget
https://www.readbyqxmd.com/read/27919786/increasing-in-cysteine-proteinase-b-expression-and-enzymatic-activity-during-in-vitro-differentiation-of-leishmania-viannia-braziliensis-first-evidence-of-modulation-during-morphological-transition
#2
Cinthia Bernardes Gomes, Franklin Souza da Silva, Karen Dos Santos Charret, Bernardo Acácio Santini Pereira, Léa Cysne Finkelstein, Raquel Santos de Souza, Luzia Monteiro de Castro Côrtes, Mirian Claudia Souza Pereira, Francisco Odêncio Rodrigues de Oliveira, Carlos Roberto Alves
Leishmania (Viannia) braziliensis presents adaptive protease-dependent mechanisms, as cysteine proteinases B (CPB). This work focuses on the expression of three cpb gene isoforms and CPB enzymatic activity during the parasite differentiation. Relative expression levels of LbrM.08.0810 gene was assessed, showing a higher quantity of transcripts in the logarithmic promastigotes phase than in the stationary promastigotes phase (> 1.5 times). The cbp gene tends to decrease during acid pH shock and increases when the temperature rises (> 1...
December 2, 2016: Biochimie
https://www.readbyqxmd.com/read/27903272/inhibition-of-bromodomain-and-extra-terminal-bet-proteins-increases-nkg2d-ligand-mica-expression-and-sensitivity-to-nk-cell-mediated-cytotoxicity-in-multiple-myeloma-cells-role-of-cmyc-irf4-mir-125b-interplay
#3
Maria Pia Abruzzese, Maria Teresa Bilotta, Cinzia Fionda, Alessandra Zingoni, Alessandra Soriani, Elisabetta Vulpis, Cristiana Borrelli, Beatrice Zitti, Maria Teresa Petrucci, Maria Rosaria Ricciardi, Rosa Molfetta, Rossella Paolini, Angela Santoni, Marco Cippitelli
BACKGROUND: Anti-cancer immune responses may contribute to the control of tumors after conventional chemotherapy, and different observations have indicated that chemotherapeutic agents can induce immune responses resulting in cancer cell death and immune-stimulatory side effects. Increasing experimental and clinical evidence highlight the importance of natural killer (NK) cells in immune responses toward multiple myeloma (MM), and combination therapies able to enhance the activity of NK cells against MM are showing promise in treating this hematologic cancer...
December 1, 2016: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/27882145/microrna-22-attenuates-myocardial-ischemia-reperfusion-injury-via-an-anti-inflammatory-mechanism-in-rats
#4
Jian Yang, Zhixing Fan, Jun Yang, Jiawang Ding, Chaojun Yang, Lihua Chen
Previous studies have reported that microRNA-22 (miR-22) may be implicated in ischemia-reperfusion (I/R)-induced myocardial injury. Our previously published data also demonstrated that miR-22 may protect against myocardial I/R injury via anti-apoptosis in rats by targeting cAMP response element-binding protein binding protein (CBP). However, the specific function of miR-22 in myocardial I/R injury is far from fully elucidated. The present study was designed to investigate another cardioprotective signaling mechanism of miR-22 in myocardial I/R injury...
November 2016: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/27881443/exploitation-of-ep300-and-crebbp-lysine-acetyltransferases-by-cancer
#5
Narsis Attar, Siavash K Kurdistani
p300 and CREB-binding protein (CBP), two homologous lysine acetyltransferases in metazoans, have a myriad of cellular functions. They exert their influence mainly through their roles as transcriptional regulators but also via nontranscriptional effects inside and outside of the nucleus on processes such as DNA replication and metabolism. The versatility of p300/CBP as molecular tools has led to their exploitation by viral oncogenes for cellular transformation and by cancer cells to achieve and maintain an oncogenic phenotype...
November 23, 2016: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/27857998/a-parp1-erk2-synergism-is-required-for-stimulation-induced-expression-of-immediate-early-genes
#6
M Cohen-Armon
A PARP1-Erk2 synergism was required to generate synaptic long-term potentiation in the CA3-CA1 hippocampal connections. This molecular mechanism was associated with the recently identified pivotal role of polyADP-ribosylation in learning. High frequency electrical stimulation of cortical and hippocampal neurons induced binding of phosphorylated Erk2 (transported into the nucleus) to the nuclear protein PARP1. PARP1-Erk2 binding induced PARP1 activation and polyADP-ribosylation of its prominent substrate, linker histone H1...
2016: Gene & Translational Bioinformatics
https://www.readbyqxmd.com/read/27812220/tissue-degeneration-following-loss-of-schistosoma-mansoni-cbp1-is-associated-with-increased-stem-cell-proliferation-and-parasite-death-in-vivo
#7
Julie N R Collins, James J Collins
Schistosomiasis is second only to malaria in terms of the global impact among diseases caused by parasites. A striking feature of schistosomes are their ability to thrive in their hosts for decades. We have previously demonstrated that stem cells, called neoblasts, promote homeostatic tissue maintenance in adult schistosomes and suggested these cells likely contribute to parasite longevity. Whether these schistosome neoblasts have functions independent of homeostatic tissue maintenance, for example in processes such as tissue regeneration following injury, remains unexplored...
November 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27799311/acetylation-modulates-il-2-receptor-signaling-in-t-cells
#8
Taku Kuwabara, Hirotake Kasai, Motonari Kondo
Ligand binding to the cognate cytokine receptors activates intracellular signaling by recruiting protein tyrosine kinases and other protein modification enzymes. However, the roles of protein modifications other than phosphorylation remain unclear. In this study, we examine a novel regulatory mechanism of Stat5, based on its acetylation. As for phosphorylation, IL-2 induces the acetylation of signaling molecules, including Stat5, in the murine T cell line CTLL-2. Stat5 is acetylated in the cytoplasm by CREB-binding protein (CBP)...
October 31, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27798150/epigenetic-regulation-of-early-and-late-response-genes-in-acute-pancreatitis
#9
Juan Sandoval, Javier Pereda, Salvador Pérez, Isabela Finamor, Azahara Vallet-Sánchez, José Luis Rodríguez, Luis Franco, Juan Sastre, Gerardo López-Rodas
Chromatin remodeling seems to regulate the patterns of proinflammatory genes. Our aim was to provide new insights into the epigenetic mechanisms that control transcriptional activation of early- and late-response genes in initiation and development of severe acute pancreatitis as a model of acute inflammation. Chromatin changes were studied by chromatin immunoprecipitation analysis, nucleosome positioning, and determination of histone modifications in promoters of proinflammatory genes in vivo in the course of taurocholate-induced necrotizing pancreatitis in rats and in vitro in rat pancreatic AR42J acinar cells stimulated with taurocholate or TNF-α...
October 19, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27777311/glucocorticoid-receptor-accelerates-but-is-dispensable-for-adipogenesis
#10
Young-Kwon Park, Kai Ge
Dexamethasone (DEX), a synthetic ligand for glucocorticoid receptor (GR), is routinely used to stimulate adipogenesis in culture. GR-depleted preadipocytes show adipogenesis defects one week after induction of differentiation. However, it has remained unclear whether GR is required for adipogenesis in vivo By deleting GR in precursors of brown adipocytes, we found unexpectedly that GR is dispensable for brown adipose tissue development in mice. In culture, GR-deficient primary or immortalized white and brown preadipocytes showed severely delayed adipogenesis one week after induction of differentiation...
October 24, 2016: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/27769780/sec8-modulates-tgf-%C3%AE-induced-emt-by-controlling-n-cadherin-via-regulation-of-smad3-4
#11
Toshiaki Tanaka, Kaoru Goto, Mitsuyoshi Iino
Sec8 is one of the subunits of the exocyst, which is an evolutionarily conserved complex of eight proteins, comprising Sec3 (EXOC1), Sec5 (EXOC2), Sec6 (EXOC3), Sec8 (EXOC4), Sec10 (EXOC5), Sec15 (EXOC6), Exo70 (EXOC7), and Exo84 (EXOC8) subunits. Sec8 knockout mice embryos initiate gastrulation but are unable to progress beyond the primitive streak stage and die shortly. During embryonic development, the first epithelial-mesenchymal transition (EMT) event occurs at gastrulation. Sec8 may be involved in the early embryonic development through EMT...
October 18, 2016: Cellular Signalling
https://www.readbyqxmd.com/read/27768872/chromatin-kinases-act-on-transcription-factors-and-histone-tails-in-regulation-of-inducible-transcription
#12
Steven Z Josefowicz, Miho Shimada, Anja Armache, Charles H Li, Rand M Miller, Shu Lin, Aerin Yang, Brian D Dill, Henrik Molina, Hee-Sung Park, Benjamin A Garcia, Jack Taunton, Robert G Roeder, C David Allis
The inflammatory response requires coordinated activation of both transcription factors and chromatin to induce transcription for defense against pathogens and environmental insults. We sought to elucidate the connections between inflammatory signaling pathways and chromatin through genomic footprinting of kinase activity and unbiased identification of prominent histone phosphorylation events. We identified H3 serine 28 phosphorylation (H3S28ph) as the principal stimulation-dependent histone modification and observed its enrichment at induced genes in mouse macrophages stimulated with bacterial lipopolysaccharide...
October 20, 2016: Molecular Cell
https://www.readbyqxmd.com/read/27759037/tgf-%C3%AE-induces-p53-smads-complex-formation-in-the-pai-1-promoter-to-activate-transcription
#13
Yuki Kawarada, Yasumichi Inoue, Fumihiro Kawasaki, Keishi Fukuura, Koichi Sato, Takahito Tanaka, Yuka Itoh, Hidetoshi Hayashi
Transforming growth factor β (TGF-β) signaling facilitates tumor development during the advanced stages of tumorigenesis, but induces cell-cycle arrest for tumor suppression during the early stages. However, the mechanism of functional switching of TGF-β is still unknown, and it is unclear whether inhibition of TGF-β signaling results amelioration or exacerbation of cancers. Here we show that the tumor suppressor p53 cooperates with Smad proteins, which are TGF-β signal transducers, to selectively activate plasminogen activator inhibitor type-1 (PAI-1) transcription...
October 19, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27699893/mapping-the-interactions-of-adenoviral-e1a-proteins-with-the-p160-nuclear-receptor-coactivator-binding-domain-of-cbp
#14
Peter Haberz, Munehito Arai, Maria A Martinez-Yamout, H Jane Dyson, Peter E Wright
Many viruses deregulate the cell and force transcription of viral genes by competing with cellular proteins for binding to the transcriptional co-activators CREB-binding protein (CBP) and p300. Through its interactions with CBP/p300 and the retinoblastoma protein, the adenovirus (AdV) early region 1A (E1A) oncoprotein hijacks the cell cycle and, in rodents, transforms the cell; the mechanistic and structural basis for these effects remain unclear. In this study we compare the affinity of protein constructs from the E1A proteins from two adenovirus serotypes, non-oncogenic AdV5 and highly oncogenic AdV12, for binding to the nuclear receptor coactivator binding domain (NCBD) of CBP...
December 2016: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/27694829/systemic-inhibition-of-creb-is-well-tolerated-in-vivo
#15
Bingbing X Li, Ryan Gardner, Changhui Xue, David Z Qian, Fuchun Xie, George Thomas, Steven C Kazmierczak, Beth A Habecker, Xiangshu Xiao
cAMP-response element binding protein (CREB) is a nuclear transcription factor activated by multiple extracellular signals including growth factors and hormones. These extracellular cues activate CREB through phosphorylation at Ser133 by various protein serine/threonine kinases. Once phosphorylated, it promotes its association with transcription coactivators CREB-binding protein (CBP) and its paralog p300 to activate CREB-dependent gene transcription. Tumor tissues of different origins have been shown to present overexpression and/or overactivation of CREB, indicating CREB as a potential cancer drug target...
October 3, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27682507/discovery-of-a-potent-and-selective-in-vivo-probe-gne-272-for-the-bromodomains-of-cbp-ep300
#16
Terry D Crawford, F Anthony Romero, Kwong Wah Lai, Vickie Tsui, Alexander M Taylor, Gladys de Leon Boenig, Cameron L Noland, Jeremy Murray, Justin Ly, Edna F Choo, Thomas L Hunsaker, Emily W Chan, Mark Merchant, Samir Kharbanda, Karen E Gascoigne, Susan Kaufman, Maureen H Beresini, Jiangpeng Liao, Wenfeng Liu, Kevin X Chen, Zhongguo Chen, Andrew R Conery, Alexandre Côté, Hariharan Jayaram, Ying Jiang, James R Kiefer, Tracy Kleinheinz, Yingjie Li, Jonathan Maher, Eneida Pardo, Florence Poy, Kerry L Spillane, Fei Wang, Jian Wang, Xiaocang Wei, Zhaowu Xu, Zhongya Xu, Ivana Yen, Laura Zawadzke, Xiaoyu Zhu, Steven Bellon, Richard Cummings, Andrea G Cochran, Brian K Albrecht, Steven Magnuson
The single bromodomain of the closely related transcriptional regulators CBP/EP300 is a target of much recent interest in cancer and immune system regulation. A co-crystal structure of a ligand-efficient screening hit and the CBP bromodomain guided initial design targeting the LPF shelf, ZA loop, and acetylated lysine binding regions. Structure-activity relationship studies allowed us to identify a more potent analogue. Optimization of permeability and microsomal stability and subsequent improvement of mouse hepatocyte stability afforded 59 (GNE-272, TR-FRET IC50 = 0...
September 28, 2016: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27673482/development-of-selective-cbp-p300-benzoxazepine-bromodomain-inhibitors
#17
Tobias A Popp, Cynthia Tallant, Catherine Rogers, Oleg Fedorov, Paul E Brennan, Susanne Müller, Stefan Knapp, Franz Bracher
CBP (CREB (cAMP responsive element binding protein) binding protein (CREBBP)) and P300 (adenovirus E1A-associated 300 kDa protein) are two closely related histone acetyltransferases (HATs) that play a key role in the regulation of gene transcription. Both proteins contain a bromodomain flanking the HAT catalytic domain that is important for the targeting of CBP/P300 to chromatin and which offeres an opportunity for the development of protein-protein interaction inhibitors. Here we present the development of CBP/P300 bromodomain inhibitors with 2,3,4,5-tetrahydro-1,4-benzoxazepine backbone, an N-acetyl-lysine mimetic scaffold that led to the recent development of the chemical probe I-CBP112...
October 13, 2016: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27647933/wnt-%C3%AE-catenin-dependent-acetylation-of-pygo2-by-cbp-p300-histone-acetyltransferase-family-members
#18
Kenneth Kao, Phillip Andrews
Pygopus 2 (Pygo2) is a chromatin effector that plays an essential role in canonical Wnt signaling associated with development and stem cell growth. Its function is to facilitate histone acetylation by recruitment of histone acetyltransferases (HATs) at active sites of β-catenin-mediated transcription. In this study, we report that Pygo2 itself, is transiently acetylated when bound to the activated TCF/β-catenin transcription complex, which correlated with β-catenin binding and Axin2 gene activation. The HATs CBP/p300, but not GCN5/PCAF targeted specific Lysine residues of the N-terminal homology domain of Pygo2 for acetylation...
September 19, 2016: Biochemical Journal
https://www.readbyqxmd.com/read/27635759/acetylation-dependent-control-of-global-poly-a-rna-degradation-by-cbp-p300-and-hdac1-2
#19
Sahil Sharma, Fabian Poetz, Marius Bruer, Thi Bach Nga Ly-Hartig, Johanna Schott, Bertrand Séraphin, Georg Stoecklin
Acetylation of histones and transcription-related factors is known to exert epigenetic and transcriptional control of gene expression. Here we report that histone acetyltransferases (HATs) and histone deacetylases (HDACs) also regulate gene expression at the posttranscriptional level by controlling poly(A) RNA stability. Inhibition of HDAC1 and HDAC2 induces massive and widespread degradation of normally stable poly(A) RNA in mammalian and Drosophila cells. Acetylation-induced RNA decay depends on the HATs p300 and CBP, which acetylate the exoribonuclease CAF1a, a catalytic subunit of the CCR4-CAF1-NOT deadenlyase complex and thereby contribute to accelerating poly(A) RNA degradation...
September 15, 2016: Molecular Cell
https://www.readbyqxmd.com/read/27633918/an-inhibitor-of-the-acetyltransferases-cbp-p300-exerts-antineoplastic-effects-on-gastrointestinal-stromal-tumor-cells
#20
Meng-Li Gu, Ya-Mei Wang, Xin-Xin Zhou, Hang-Ping Yao, Song Zheng, Zun Xiang, Feng Ji
Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasm featured by activated mutations of KIT and PDGFRA. Although overall survival rates have greatly improved by the development of receptor tyrosine kinase inhibitors, most patients ultimately acquire resistance due to secondary mutations of KIT or PDGFRA. Inhibition of the histone acetyltransferases (HATs) CREB‑binding protein (CBP) and p300 results in antineoplastic effects in various cancers. To determine whether CBP/p300 can serve as an antineoplastic target for GISTs, specific short interfering RNA sequences and the selective HAT inhibitor C646 were administered to GIST882 cells...
September 12, 2016: Oncology Reports
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