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https://www.readbyqxmd.com/read/28713342/nf-%C3%AE%C2%BAbp50-and-hdac1-interaction-is-implicated-in-the-host-tolerance-to-infection-mediated-by-the-bacterial-quorum-sensing-signal-2-aminoacetophenone
#1
Arunava Bandyopadhaya, Amy Tsurumi, Laurence G Rahme
Some bacterial quorum sensing (QS) small molecules are important mediators of inter-kingdom signaling and impact host immunity. The QS regulated small volatile molecule 2-aminoacetophenone (2-AA), which has been proposed as a biomarker of Pseudomonas aeruginosa colonization in chronically infected human tissues, is critically involved in "host tolerance training" that involves a distinct molecular mechanism of host chromatin regulation through histone deacetylase (HDAC)1. 2-AA's epigenetic reprogramming action enables host tolerance to high bacterial burden and permits long-term presence of P...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28700938/golgi-outpost-synthesis-impaired-by-toxic-polyglutamine-proteins-contributes-to-dendritic-pathology-in-neurons
#2
Chang Geon Chung, Min Jee Kwon, Keun Hye Jeon, Do Young Hyeon, Myeong Hoon Han, Jeong Hyang Park, In Jun Cha, Jae Ho Cho, Kunhyung Kim, Sangchul Rho, Gyu Ree Kim, Hyobin Jeong, Jae Won Lee, TaeSoo Kim, Keetae Kim, Kwang Pyo Kim, Michael D Ehlers, Daehee Hwang, Sung Bae Lee
Dendrite aberration is a common feature of neurodegenerative diseases caused by protein toxicity, but the underlying mechanisms remain largely elusive. Here, we show that nuclear polyglutamine (polyQ) toxicity resulted in defective terminal dendrite elongation accompanied by a loss of Golgi outposts (GOPs) and a decreased supply of plasma membrane (PM) in Drosophila class IV dendritic arborization (da) (C4 da) neurons. mRNA sequencing revealed that genes downregulated by polyQ proteins included many secretory pathway-related genes, including COPII genes regulating GOP synthesis...
July 11, 2017: Cell Reports
https://www.readbyqxmd.com/read/28680062/linking-functions-an-additional-role-for-an-intrinsically-disordered-linker-domain-in-the-transcriptional-coactivator-cbp
#3
Sara Contreras-Martos, Alessandro Piai, Simone Kosol, Mihaly Varadi, Angela Bekesi, Pierre Lebrun, Alexander N Volkov, Kris Gevaert, Roberta Pierattelli, Isabella C Felli, Peter Tompa
The multi-domain transcriptional coactivators CBP/p300 integrate a multitude of signaling inputs, interacting with more than 400 proteins via one or more of their globular domains. While CBP/p300 function is typically considered in terms of these structured domains, about half of the protein consists of intrinsically disordered regions (IDRs) of varying length. However, these IDRs have only been thought of as linkers that allow flexible spatial arrangement of the structured domains, but recent studies have shown that similar IDRs mediate specific and critical interactions in other proteins...
July 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28638460/zeb1-mediates-drug-resistance-and-emt-in-p300-deficient-crc
#4
Darina Lazarova, Michael Bordonaro
We discuss the hypothesis that ZEB1-Wnt-p300 signaling integrates epithelial to mesenchymal transition (EMT) and resistance to histone deacetylase inhibitors (HDACis) in colorectal cancer (CRC) cells. The HDACi butyrate, derived from dietary fiber, has been linked to CRC prevention, and other HDACis have been proposed as therapeutic agents against CRC. We have previously discussed that resistance to butyrate likely contributes to colonic carcinogenesis, and we have demonstrated that butyrate resistance leads to cross-resistance to cancer therapeutic HDACis...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28627884/hydrogen-deuterium-exchange-mass-spectrometry-reveals-calcium-binding-properties-and-allosteric-regulation-of-downstream-regulatory-element-antagonist-modulator-dream
#5
Jun Zhang, Jing Li, Theodore A Craig, Rajiv Kumar, Michael L Gross
Downstream regulatory element antagonist modulator (DREAM) is an EF-hand Ca(2+)-binding protein that also binds to a specific DNA sequence, downstream regulatory elements (DRE), and thereby regulates transcription in a calcium-dependent fashion. DREAM binds to DRE in the absence of Ca(2+) but detaches from DRE under Ca(2+) stimulation, allowing gene expression. The Ca(2+) binding properties of DREAM and the consequences of the binding on protein structure are key to understanding the function of DREAM. Here we describe the application of hydrogen-deuterium exchange mass spectrometry (HDX-MS) and site-directed mutagenesis to investigate the Ca(2+) binding properties and the subsequent conformational changes of full-length DREAM...
July 3, 2017: Biochemistry
https://www.readbyqxmd.com/read/28625977/p300-mediated-acetylation-of-the-notch-effector-transcription-factor-maml-1-recruits-nack-to-initiate-notch-dependent-transcription
#6
Ke Jin, Wen Zhou, Xiaoqing Han, Zhiqiang Wang, Bin Li, Shawn Jeffries, Wensi Tao, David J Robbins, Anthony J Capobianco
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) is a critical co-activator of Notch signaling and binds to the Notch1 ternary complex. Herein we report that p300 and CBP acetylate mastermind-like transcriptional coactivator 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...
June 16, 2017: Cancer Research
https://www.readbyqxmd.com/read/28616572/reversible-lysine-acetylation-regulates-nuclear-translocation-of-tyrrs-to-counteract-genotoxic-oxidative-stress
#7
Chaoqun Li, Wei Yu
Aminoacyl-tRNA synthetases, catalyzing the first step of protein synthesis, have been shown to involve with multiple additional physiologic responses. Here, we summarize our findings that p300/CBP-Associated Factor and Sirtuin 1 play the reversible acetylation role in regulating the nuclear translocation of Tyrosyl-tRNA synthetase and activating transcription factor E2F1, thus facilitating the repair of damaged DNA.
2017: Molecular & Cellular Oncology
https://www.readbyqxmd.com/read/28589097/ago2-negatively-regulates-type-i-interferon-signaling-pathway-by-competition-binding-irf3-with-cbp-p300
#8
Shengyu Wang, Xin Sun, Chenyang Yi, Dan Zhang, Xian Lin, Xiaomei Sun, Huanchun Chen, Meilin Jin
Viral infection triggers a series of signaling cascades and host innate immune responses, including interferon (IFN) production, which depends on coordinated activity of multiple transcription factors. IFN regulatory factor 3 (IRF3) and transcriptional coactivator CREB binding protein (CBP) and/or p300 are core factors that participate in transcriptional complex formation in the nucleus. In general, cells balance the production of IFNs through suppressive and stimulative mechanisms, but viral infections can disrupt such equilibrium...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28580166/mof-as-an-evolutionarily-conserved-histone-crotonyltransferase-and-transcriptional-activation-by-histone-acetyltransferase-deficient-and-crotonyltransferase-competent-cbp-p300
#9
Xiaoguang Liu, Wei Wei, Yuting Liu, Xueli Yang, Jian Wu, Yang Zhang, Qiao Zhang, Tieliu Shi, James X Du, Yingming Zhao, Ming Lei, Jin-Qiu Zhou, Jiwen Li, Jiemin Wong
Recent studies indicate that histones are subjected to various types of acylation including acetylation, propionylation and crotonylation. CBP and p300 have been shown to catalyze multiple types of acylation but are not conserved in evolution, raising the question as to the existence of other enzymes for histone acylation and the functional relationship between well-characterized acetylation and other types of acylation. In this study, we focus on enzymes catalyzing histone crotonylation and demonstrate that among the known histone acetyltransferases, MOF, in addition to CBP and p300, also possesses histone crotonyltransferase (HCT) activity and this activity is conserved in evolution...
2017: Cell Discovery
https://www.readbyqxmd.com/read/28576496/identification-of-zinc-finger-transcription-factor-egr2-as-a-novel-acetylated-protein
#10
Kota Noritsugu, Akihiro Ito, Yoichi Nakao, Minoru Yoshida
EGR2 is a zinc finger transcription factor that regulates myelination in the peripheral nervous system and T cell anergy. The transcriptional activity of EGR2 is known to be regulated by its co-activators and/or co-repressors. Although the activity of transcription factors is generally regulated not only by interactions with co-regulators but also posttranslational modifications including acetylation, little is known about posttranslational modifications of EGR2. Here we show that EGR2 is a novel acetylated protein...
May 30, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28547133/hsf1-acetylation-decreases-its-transcriptional-activity-and-enhances-glucolipotoxicity-induced-apoptosis-in-rat-and-human-beta-cells
#11
Indri Purwana, Jun J Liu, Bernard Portha, Jean Buteau
AIMS/HYPOTHESIS: Heat shock factor protein 1 (HSF1) is a transcription factor that regulates the expression of key molecular chaperones, thereby orchestrating the cellular response to stress. This system was recently implicated in the control of insulin sensitivity and is therefore being scrutinised as a novel therapeutic avenue for type 2 diabetes. However, the regulation and biological actions of HSF1 in beta cells remain elusive. Herein, we sought to investigate the regulation of HSF1 in pancreatic beta cells and to study its potential role in cell survival...
May 25, 2017: Diabetologia
https://www.readbyqxmd.com/read/28534508/utx-promotes-hormonally-responsive-breast-carcinogenesis-through-feed-forward-transcription-regulation-with-estrogen-receptor
#12
G Xie, X Liu, Y Zhang, W Li, S Liu, Z Chen, B Xu, J Yang, L He, Z Zhang, T Jin, X Yi, L Sun, Y Shang, J Liang
UTX is implicated in embryonic development and lineage specification. However, how this X-linked histone demethylase contributes to the occurrence and progression of breast cancer remains to be clarified. Here we report that UTX is physically associated with estrogen receptor (ER) and functions in ER-regulated transcription. We showed that UTX coordinates with JHDM1D and CBP to direct H3K27 methylation-acetylation transition and to create a permissive chromatin state on ER targets. Genome-wide analysis of the transcriptional targets of UTX by ChIP-seq identified a set of genes such as chemokine receptor CXCR4 that are intimately involved in breast cancer tumorigenesis and metastasis...
May 22, 2017: Oncogene
https://www.readbyqxmd.com/read/28523540/rubinstein-taybi-syndrome-and-epigenetic-alterations
#13
Edward Korzus
Rubinstein-Taybi syndrome (RSTS) is a rare genetic disorder in humans characterized by growth and psychomotor delay, abnormal gross anatomy, and mild to severe mental retardation (Rubinstein and Taybi, Am J Dis Child 105:588-608, 1963, Hennekam et al., Am J Med Genet Suppl 6:56-64, 1990). RSTS is caused by de novo mutations in epigenetics-associated genes, including the cAMP response element-binding protein (CREBBP), the gene-encoding protein referred to as CBP, and the EP300 gene, which encodes the p300 protein, a CBP homologue...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28513807/the-nuclear-pore-protein-nup153-associates-with-chromatin-and-regulates-cardiac-gene-expression-in-dystrophic-mdx-hearts
#14
Simona Nanni, Agnese Re, Cristian Ripoli, Aoife Gowran, Patrizia Nigro, Domenico D'Amario, Antonio Amodeo, Filippo Crea, Claudio Grassi, Alfredo Pontecorvi, Antonella Farsetti, Claudia Colussi
Aims: Beyond the control of nuclear-cytoplasmic trafficking nucleoporins regulate gene expression and are involved in cardiac diseases. Notably, a number of cardiovascular disorders have been linked to alterations in epigenetic mechanisms. Here we aimed to determine the contribution of Nup153 to the epigenetic alterations occurring in cardiomyopathy of dystrophin-deficient mdx mice (C57BL/10ScSn-Dmd mdx /J). Methods and results: Nup153 was lysine-acetylated and its expression was significantly increased at protein level in mdx hearts compared with controls...
November 1, 2016: Cardiovascular Research
https://www.readbyqxmd.com/read/28501104/knockdown-of-cbp-p300-interacting-transactivator-with-glu-asp-rich-carboxy-terminal-domain-2-inhibits-cell-division-and-increases-apoptosis-in-gastric-cancer
#15
Ze Tang, Gan He, Jie Xu, Li Zhongfu
BACKGROUND: Cbp/P300-interacting transactivator with Glu/Asp-rich carboxy-terminal domain 2 (CITED2) is a pleiotropic protein associated with numerous cell functions, including transcription and differentiation. The role of CITED2 has been investigated in a number of malignancies; however, the roles of this protein in gastric cancers remain unclear. Therefore, we determined the role of CITED2 in gastric cancers. MATERIALS AND METHODS: Gastric cancer cell lines (MKN74, MKN28, 7901, and AGS) were used to assess CITED2 transcript levels...
May 1, 2017: Journal of Surgical Research
https://www.readbyqxmd.com/read/28488757/stimulation-of-pol-iii-dependent-5s-rrna-and-u6-snrna-gene-expression-by-ap-1-transcription-factors
#16
Richa Ahuja, Vijay Kumar
RNA polymerase III transcribes structurally diverse group of essential noncoding RNAs including 5S ribosomal RNA (5SrRNA) and U6 snRNA. These noncoding RNAs are involved in RNA processing and ribosome biogenesis, thus, coupling Pol III activity to the rate of protein synthesis, cell growth, and proliferation. Even though a few Pol II-associated transcription factors have been reported to participate in Pol III-dependent transcription, its activation by activator protein 1 (AP-1) factors, c-Fos and c-Jun, has remained unexplored...
May 10, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28474232/ets-targeted-therapy-can-it-substitute-for-mek-inhibitors
#17
REVIEW
Osamu Tetsu, Frank McCormick
BACKGROUND: The RAS/MAPK pathway has been intensively studied in cancer. Constitutive activation of ERK1 and ERK2 is frequently found in cancer cells from a variety of tissues. In clinical practice and clinical trials, small molecules targeting receptor tyrosine kinases or components in the MAPK cascade are used for treatment. MEK1 and MEK2 are ideal targets because these enzymes are physiologically important and have narrow substrate specificities and distinctive structural characteristics...
December 2017: Clinical and Translational Medicine
https://www.readbyqxmd.com/read/28460484/the-%C3%AE-catenin-cbp-antagonist-icg-001-inhibits-pediatric-glioma-tumorigenicity-in-a-wnt-independent-manner
#18
Maria Wiese, Neele Walther, Christopher Diederichs, Fabian Schill, Sebastian Monecke, Gabriela Salinas, Dominik Sturm, Stefan M Pfister, Ralf Dressel, Steven A Johnsen, Christof M Kramm
Pediatric high-grade gliomas (pedHGG) belong to the most aggressive cancers in children with a poor prognosis due to a lack of efficient therapeutic strategies. The β-catenin/Wnt-signaling pathway was shown to hold promising potential as a treatment target in adult high-grade gliomas by abrogating tumor cell invasion and the acquisition of stem cell-like characteristics. Since pedHGG differ from their adult counterparts in genetically and biologically we aimed to investigate the effects of β-catenin/Wnt-signaling pathway-inhibition by the β-catenin/CBP antagonist ICG-001 in pedHGG cell lines...
April 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28442062/retinoic-acid-triggers-c-kit-gene-expression-in-spermatogonial-stem-cells-through-an-enhanceosome-constituted-between-transcription-factor-binding-sites-for-retinoic-acid-response-element-rare-spleen-focus-forming-virus-proviral-integration-oncogene-spfi1-pu
#19
Swanand Koli, Ayan Mukherjee, Kudumula Venkata Rami Reddy
Restricted availability of retinoic acid (RA) in the testicular milieu regulates transcriptional activity of c-kit (KIT, CD117), which aids in the determination of spermatogonial stem-cell differentiation. The effect of RA on c-kit has been reported previously, but its mode of genomic action remains unresolved. We studied the molecular machinery guiding RA responsiveness to the c-kit gene using spermatogonial stem-cell line C18-4 and primary spermatogonial cells. A novel retinoic acid response element (RARE) positioned at -989 nucleotides upstream of the transcription start site (TSS) was identified, providing a binding site for a dimeric RA receptor (i...
March 2017: Reproduction, Fertility, and Development
https://www.readbyqxmd.com/read/28416608/hyper-o-glcnacylation-activates-nuclear-factor-%C3%AE%C2%BA-light-chain-enhancer-of-activated-b-cells-nf-%C3%AE%C2%BAb-signaling-through-interplay-with-phosphorylation-and-acetylation
#20
Zhiyuan Ma, Robert J Chalkley, Keith Vosseller
O-GlcNAcylation is the covalent addition of an O-linked β-N-acetylglucosamine (O-GlcNAc) sugar moiety to hydroxyl groups of serine/threonine residues of cytosolic and nuclear proteins. O-GlcNAcylation, analogous to phosphorylation, plays critical roles in gene expression through direct modification of transcription factors, such as NF-κB. Aberrantly increased NF-κB O-GlcNAcylation has been linked to NF-κB constitutive activation and cancer development. Therefore, it is of a great biological and clinical significance to dissect the molecular mechanisms that tune NF-κB activity...
June 2, 2017: Journal of Biological Chemistry
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