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DNA-binding proteins

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https://www.readbyqxmd.com/read/29346775/brd4-promotes-dna-repair-and-mediates-the-formation-of-tmprss2-erg-gene-rearrangements-in-prostate-cancer
#1
Xiangyi Li, GuemHee Baek, Susmita G Ramanand, Adam Sharp, Yunpeng Gao, Wei Yuan, Jon Welti, Daniel N Rodrigues, David Dolling, Ines Figueiredo, Semini Sumanasuriya, Mateus Crespo, Adam Aslam, Rui Li, Yi Yin, Bipasha Mukherjee, Mohammed Kanchwala, Ashley M Hughes, Wendy S Halsey, Cheng-Ming Chiang, Chao Xing, Ganesh V Raj, Sandeep Burma, Johann de Bono, Ram S Mani
BRD4 belongs to the bromodomain and extraterminal (BET) family of chromatin reader proteins that bind acetylated histones and regulate gene expression. Pharmacological inhibition of BRD4 by BET inhibitors (BETi) has indicated antitumor activity against multiple cancer types. We show that BRD4 is essential for the repair of DNA double-strand breaks (DSBs) and mediates the formation of oncogenic gene rearrangements by engaging the non-homologous end joining (NHEJ) pathway. Mechanistically, genome-wide DNA breaks are associated with enhanced acetylation of histone H4, leading to BRD4 recruitment, and stable establishment of the DNA repair complex...
January 16, 2018: Cell Reports
https://www.readbyqxmd.com/read/29346508/oroxylin-a%C3%AF-a-natural-compound-mitigates-the-negative-effects-of-tnf%C3%AE-treated-acute-myelogenous-leukemia-cells
#2
Hui Li, Na Lu, Xiaoxuan Yu, Xiao Liu, Po Hu, Yu Zhu, Le Shen, Jingyan Xu, Zhiyu Li, Qinglong Guo, Hui Hui
Tumor necrosis factor alpha (TNFα) is a complicated cytokine which is involved in proliferation and differentiation of acute myelogenous leukemia (AML) cells through a poorly understood mechanism. Mechanistic studies indicate that TNFα induced binding of PI3K subunit p85α to N-terminal truncated nuclear receptor RXRα (tRXRα) proteins, and activated AKT. The activated PI3K/AKT pathway negatively regulated differentiation of AML cells through the up-regulation of c-Myc. In addition, TNFα also induced activation of nuclear factor κB (NF-κB), a nuclear transcription factor which was shown to promote cell proliferation...
January 13, 2018: Carcinogenesis
https://www.readbyqxmd.com/read/29346433/vault-rnas-partially-induces-drug-resistance-of-human-tumor-cells-mcf-7-by-binding-to-the-rna-dna-binding-protein-psf-and-inducing-oncogene-gage6
#3
Jianjun Chen, Hui OuYang, Xuemei An, Shixi Liu
BACKGROUND: Vault is the largest nonicosahedral cytosolic nucleoprotein particle, which is widely involved in induction of chemoresistance and lead to failure in long-term chemotherapy. Vault contains three different major vault proteins (MVPs) and four vault RNAs paralogues (vtRNAs, vtRNA1-1, vtRNA1-2, vtRNA1-3 and vtRNA2-1). Disruption of the MVPs do not induce hypersensitivity while expression of vtRNAs contributes to cells' drug resistance, indicates that vtRNAs, but not MVPs play an important role in causing drug resistance...
2018: PloS One
https://www.readbyqxmd.com/read/29345941/dual-signaling-dna-electrochemistry-an-approach-to-understand-dna-interfaces
#4
Saimon Moraes Silva, Roya Tavallaie, Vinicius R Gonçales, Robert H Utama, Mehran B Kashi, D Brynn Hibbert, Richard D Tilley, J Justin Gooding
Electrochemical DNA biosensors composed of a redox marker modified nucleic acid probe tethered to a solid electrode is a common experimental construct for detecting DNA and RNA targets, proteins, inorganic ions, and even small molecules. This class of biosensors generally relies on the binding-induced conformational changes in the distance of the redox marker relative to the electrode surface such that the charge transfer is altered. The conventional design is to attach the redox species to the distal end of a surface-bound nucleic acid strand...
January 18, 2018: Langmuir: the ACS Journal of Surfaces and Colloids
https://www.readbyqxmd.com/read/29345419/targeting-bcl2-gene-promoter-g-quadruplex-with-a-new-class-of-furopyridazinone-based-molecules
#5
Jussara Amato, Alessia Pagano, Domenica Capasso, Sonia Di Gaetano, Mariateresa Giustiniano, Ettore Novellino, Antonio Randazzo, Bruno Pagano
Targeting of G-quadruplex-forming DNA in BCL2 gene promoter to inhibit the expression of anti-apoptotic Bcl-2 protein represents an attractive opportunity in cancer treatment. So far, efforts made in the discovery of molecules able to target BCL2 G-quadruplex mainly succeeded in the identification of ligands with poor drug-like properties. Here, a small series of furo[2,3-d]pyridazin-4(5H)-one derivatives were evaluated as a new class of drug-like G-quadruplex-targeting compounds. Biophysical studies showed that two derivatives could effectively bind to BCL2 G-quadruplex with good selectivity...
January 18, 2018: ChemMedChem
https://www.readbyqxmd.com/read/29345269/tributyltin-induces-epigenetic-changes-and-decreases-the-expression-of-nuclear-respiratory-factor-1
#6
Saki Hanaoka, Keishi Ishida, Saki Tanaka, Shuichiro Sakamoto, Katsuhiro Okuda, Seigo Sanoh, Shigeru Ohta, Yaichiro Kotake
Tributyltin (TBT), a common organotin environmental pollutant, has been widely used as a component of marine antifouling paints. We previously reported that exposure to TBT inhibits the expression and DNA binding of nuclear respiratory factor-1 (NRF-1) and causes neurotoxicity. In the present study, we focused on the epigenetic effects of TBT and investigated whether TBT decreases NRF-1 expression via epigenetic modifications in SH-SY5Y human neuroblastoma cells. First, we found that exposure to 300 nM TBT decreases NRF-1 expression...
January 18, 2018: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/29344693/triplet-based-codon-organization-optimizes-the-impact-of-synonymous-mutation-on-nucleic-acid-molecular-dynamics
#7
Gregory A Babbitt, Erin E Coppola, Jamie S Mortensen, Patrick X Ekeren, Cosmo Viola, Dallan Goldblatt, André O Hudson
Since the elucidation of the genetic code almost 50 years ago, many nonrandom aspects of its codon organization remain only partly resolved. Here, we investigate the recent hypothesis of 'dual-use' codons which proposes that in addition to allowing adjustment of codon optimization to tRNA abundance, the degeneracy in the triplet-based genetic code also multiplexes information regarding DNA's helical shape and protein-binding dynamics while avoiding interference with other protein-level characteristics determined by amino acid properties...
January 17, 2018: Journal of Molecular Evolution
https://www.readbyqxmd.com/read/29344347/epigenetic-alterations-in-tramp-mice-epigenome-dna-methylation-profiling-using-medip-seq
#8
Wenji Li, Ying Huang, Davit Sargsyan, Tin Oo Khor, Yue Guo, Limin Shu, Anne Yuqing Yang, Chengyue Zhang, Ximena Paredes-Gonzalez, Michael Verzi, Ronald P Hart, Ah-Ng Kong
Purpose: We investigated the genomic DNA methylation profile of prostate cancer in transgenic adenocarcinoma of the mouse prostate (TRAMP) cancer model and to analyze the crosstalk among targeted genes and the related functional pathways. Methods: Prostate DNA samples from 24-week-old TRAMP and C57BL/6 male mice were isolated. The DNA methylation profiles were analyzed by methylated DNA immunoprecipitation (MeDIP) followed by next-generation sequencing (MeDIP-seq)...
2018: Cell & Bioscience
https://www.readbyqxmd.com/read/29344296/cdk16-phosphorylates-and-degrades-p53-to-promote-radioresistance-and-predicts-prognosis-in-lung-cancer
#9
Jie Xie, Yan Li, Ke Jiang, Kaishun Hu, Sheng Zhang, Xiaorong Dong, Xiaofang Dai, Li Liu, Tao Zhang, Kunyu Yang, Kai Huang, Junjie Chen, Shaojun Shi, Yu Zhang, Gang Wu, Shuangbing Xu
Rationale: Radioresistance is considered the main cause of local relapse in lung cancer. However, the molecular mechanisms of radioresistance remain poorly understood. This study investigates the role of CDK16 in radioresistance of human lung cancer cells. Methods: The expression levels of CDK16 were determined by immunohistochemistry in lung cancer tissues and adjacent normal lung tissues. Immunoprecipitation assay and GST pulldown were utilized to detect the protein-protein interaction. The phosphorylation of p53 was evaluated by in vitro kinase assay...
2018: Theranostics
https://www.readbyqxmd.com/read/29343810/mitochondrial-dna-damage-and-subsequent-activation-of-z-dna-binding-protein-1-links-oxidative-stress-to-inflammation-in-epithelial-cells
#10
Bartosz Szczesny, Michela Marcatti, Akbar Ahmad, Mauro Montalbano, Attila Brunyánszki, Sofia-Iris Bibli, Andreas Papapetropoulos, Csaba Szabo
This report identifies mitochondrial DNA (mtDNA) as a target and active mediator that links low-level oxidative stress to inflammatory response in pulmonary epithelial cells. Extrusion of mtDNA into the bronchoalveolar lavage fluid occurs as an early event in mice subjected to cigarette smoke injury, concomitantly with the depletion of mtDNA in the lung tissue. In cultured lung epithelial cells, prolonged, low-level oxidative stress damages the mtDNA, without any detectable damage to the nuclear DNA. In turn, cellular depletion of the mtDNA occurs, together with a transient remodeling of cellular bioenergetics and morphology - all without any detectable impairment in overall cell viability...
January 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29343791/single-plasmid-systems-for-inducible-dual-protein-expression-and-for-crispr-cas9-crispri-gene-regulation-in-lactic-acid-bacterium-lactococcus-lactis
#11
Aleš Berlec, Katja Škrlec, Janja Kocjan, Maria Olenic, Borut Štrukelj
Lactococcus lactis is a food-grade lactic acid bacterium that is used in the dairy industry as a cell factory and as a host for recombinant protein expression. The nisin-controlled inducible expression (NICE) system is frequently applied in L. lactis; however new tools for its genetic modification are highly desirable. In this work NICE was adapted for dual protein expression. Plasmid pNZDual, that contains two nisin promoters and multiple cloning sites (MCSs), and pNZPolycist, that contains a single nisin promoter and two MCSs separated by the ribosome binding site, were constructed...
January 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29343641/degradation-of-fbxo31-by-apc-c-is-regulated-by-akt-and-atm-mediated-phosphorylation
#12
Srinadh Choppara, Sunil K Malonia, Ganga Sankaran, Michael R Green, Manas Kumar Santra
The F-box protein FBXO31 is a tumor suppressor that is encoded in 16q24.3, for which there is loss of heterozygosity in various solid tumors. FBXO31 serves as the substrate-recognition component of the SKP/Cullin/F-box protein class of E3 ubiquitin ligases and has been shown to direct degradation of pivotal cell-cycle regulatory proteins including cyclin D1 and the p53 antagonist MDM2. FBXO31 levels are normally low but increase substantially following genotoxic stress through a mechanism that remains to be determined...
January 17, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29343574/novel-human-polyomavirus-non-coding-control-regions-differ-in-bi-directional-gene-expression-according-to-host-cell-large-t-antigen-expression-and-clinically-occurring-rearrangements
#13
Elvis T Ajuh, Zongsong Wu, Emma Kraus, Fabian H Weissbach, Tobias Bethge, Rainer Gosert, Nicole Fischer, Hans H Hirsch
Human polyomavirus (HPyV) DNA genomes contain three regions denoted early viral gene region (EVGR) encoding the regulatory T-antigens and one microRNA, late viral gene region (LVGR) encoding the structural Vp capsid proteins, and non-coding control region (NCCR). The NCCR harbours the origin of viral genome replication and bi-directional promoter/enhancer functions governing EVGR- and LVGR-expression on opposite DNA strands. Despite principle similarities, HPyV-NCCRs differ in length, sequence, and architecture...
January 17, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29343569/myxoma-virus-m083-is-a-virulence-factor-which-mediates-systemic-dissemination
#14
A M Wolfe, K M Dunlap, A C Smith, M Y Bartee, E Bartee
Poxviruses are large, DNA viruses whose protein capsid is surrounded by one or more lipid envelopes. Embedded into these lipid envelopes are three conserved viral proteins which are thought to mediate binding of virions to target cells. While the function of these proteins has been studied in vitro, their specific roles during the pathogenesis of poxviral disease remains largely unclear. Here we present data demonstrating that the putative chondroitin binding protein, M083, from the leporipoxvirus myxoma is a significant virulence factor during infection of susceptible Oryctolagus rabbits...
January 17, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29343567/parainfluenza-virus-infection-sensitizes-cancer-cells-to-dna-damaging-agents-implications-for-oncolytic-virus-therapy
#15
Candace R Fox, Griffith D Parks
We have previously shown that the Parainfluenza virus 5 (PIV5) mutant P/V-CPI- is restricted for spread in normal cells but not in cancer cells in vitro and is effective at reducing tumor burden in mouse model systems. Here we show that P/V-CPI- infection of human laryngeal cancer HEp-2 cells results in the majority of the cells dying, but unexpectedly, over time there is an emergence of a population of cells which survive as P/V-CPI- persistently infected (PI) cells. P/V-CPI- PI cells had elevated levels of basal caspase activation, and viability was highly dependent on activity of cellular inhibitors of apoptosis (IAPs) such as Survivin and XIAP...
January 17, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29342954/a-built-in-cpg-adjuvant-in-rsv-f-protein-dna-vaccine-drives-a-th1-polarized-and-enhanced-protective-immune-response
#16
Yao Ma, Yue-Ying Jiao, Yun-Zhou Yu, Nan Jiang, Ying Hua, Xiu-Juan Zhang, Yuan-Hui Fu, Xiang-Lei Peng, Yan-Peng Zheng, Larry J Anderson, Jin-Sheng He
Human respiratory syncytial virus (RSV) is the most significant cause of acute lower respiratory infection in children. However, there is no licensed vaccine available. Here, we investigated the effect of five or 20 copies of C-Class of CpG ODN (CpG-C) motif incorporated into a plasmid DNA vaccine encoding RSV fusion (F) glycoprotein on the vaccine-induced immune response. The addition of CpG-C motif enhanced serum binding and virus-neutralizing antibody responses in BALB/c mice immunized with the DNA vaccines...
January 15, 2018: Viruses
https://www.readbyqxmd.com/read/29342503/the-molecular-basis-for-dysregulated-activation-of-nkx2-5-in-vascular-remodelling-of-systemic-sclerosis
#17
Athina Dritsoula, Ioannis Papaioannou, Sandra G Guerra, Carmen Fonseca, Javier Martin, Ariane L Herrick, David J Abraham, Christopher P Denton, Markella Ponticos
OBJECTIVE: NKX2-5 is a homeobox transcription factor required for the formation of the heart and vessels during development, with significant postnatal downregulation and reactivation in disease states characterised by vascular remodelling. In this study, we sought to investigate mechanisms that activate NKX2-5 expression in diseased vessels, such as scleroderma associated pulmonary hypertension (SSc-PH), and identify genetic variability that potentially underlies susceptibility to specific vascular complications...
January 17, 2018: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/29341597/the-wyl-domain-of-the-pif1-helicase-from-the-thermophilic-bacterium-thermotoga-elfii-is-an-accessory-single-stranded-dna-binding-module
#18
Nicholas M Andis, Christopher W Sausen, Ashna Alladin, Matthew Bochman
PIF1 family helicases are conserved from bacteria to man. With the exception of the well-studied yeast PIF1 helicases (e.g., ScPif1 and ScRrm3), however, very little is known about how these enzymes help maintain genome stability. Indeed, we lack a basic understanding of the protein domains found N- and C-terminal to the characteristic central PIF1 helicase domain in these proteins. Here, using chimeric constructs, we show that the ScPif1 and ScRrm3 helicase domains are interchangeable and that the N-terminus of ScRrm3 is important for its function in vivo...
January 17, 2018: Biochemistry
https://www.readbyqxmd.com/read/29341462/dna-origami-scaffolds-as-templates-for-functional-tetrameric-kir3-k-channels
#19
Tatsuki Kurokawa, Shigeki Kiyonaka, Eiji Nakata, Masayuki Endo, Shohei Koyama, Emiko Mori, Nam Ha Tran, Huyen Dinh, Yuki Suzuki, Kumi Hidaka, Masaaki Kawata, Chikara Sato, Hiroshi Sugiyama, Takashi Morii, Yasuo Mori
In native systems, scaffolding proteins play important roles in assembling proteins into complexes to transduce signals. This concept is yet to be incorporated in assembling functional transmembrane protein complexes in artificial systems. To address this issue, DNA origami has potentiality to serve as scaffolds that arrange proteins at specific positions in complexes. Here, we report that Kir3 K+ channel proteins are assembled through zinc-finger protein (ZFP)-adaptors at specific locations on DNA origami scaffolds...
January 16, 2018: Angewandte Chemie
https://www.readbyqxmd.com/read/29340031/analyzing-the-influence-of-kinase-inhibitors-on-dna-repair-by-differential-proteomics-of-chromatin-interacting-proteins-and-nuclear-phospho-proteins
#20
Lisa Gleißner, Marcel Kwiatkowski, Laura Myllynen, Pascal Steffen, Cordula Petersen, Kai Rothkamm, Hartmut Schlüter, Malte Kriegs
The combination of radiotherapy and pharmacological inhibition of cellular signal transduction pathways offers promising strategies for enhanced cancer cell inactivation. However, the molecular effects of kinase inhibitors especially on DNA damage detection and repair after X-irradiation have to be understood to facilitate the development of efficient and personalized treatment regimens. Therefore, we applied differential proteomics for analyzing inhibitor-induced changes in either chromatin-bound or phosphorylated nuclear proteins...
December 19, 2017: Oncotarget
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