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Synthetic transcriptional factor

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https://www.readbyqxmd.com/read/28073919/trub1-is-the-predominant-pseudouridine-synthase-acting-on-mammalian-mrna-via-a-predictable-and-conserved-code
#1
Modi Safra, Ronit Nir, Daneyal Farouq, Schraga Schwartz
Following synthesis, RNA can be modified with over 100 chemically distinct modifications, which can potentially regulate RNA expression post-transcriptionally. Pseudouridine (Ψ) was recently established to be widespread and dynamically regulated on yeast mRNA, but less is known about Ψ presence, regulation and biogenesis in mammalian mRNA. Here, we sought to characterize the Ψ landscape on mammalian mRNA, to identify the main Ψ-synthases (PUSs) catalyzing Ψ formation, and to understand the factors governing their specificity towards selected targets...
January 10, 2017: Genome Research
https://www.readbyqxmd.com/read/28065574/a-blueprint-for-a-synthetic-genetic-feedback-controller-to-reprogram-cell-fate
#2
Domitilla Del Vecchio, Hussein Abdallah, Yili Qian, James J Collins
To artificially reprogram cell fate, experimentalists manipulate the gene regulatory networks (GRNs) that maintain a cell's phenotype. In practice, reprogramming is often performed by constant overexpression of specific transcription factors (TFs). This process can be unreliable and inefficient. Here, we address this problem by introducing a new approach to reprogramming based on mathematical analysis. We demonstrate that reprogramming GRNs using constant overexpression may not succeed in general. Instead, we propose an alternative reprogramming strategy: a synthetic genetic feedback controller that dynamically steers the concentration of a GRN's key TFs to any desired value...
January 3, 2017: Cell Systems
https://www.readbyqxmd.com/read/28059499/inactivation-of-the-nuclear-orphan-receptor-coup-tfii-by-small-chemicals
#3
Rémy Le Guével, Frédérik Oger, Celia P Martinez-Jimenez, Maud Bizot, Céline Gheeraert, François Firmin, Maheul Ploton, Miroslava Kretova, Gaëlle Palierne, Bart Staels, Peter Barath, Iannis Talianidis, Philippe Lefebvre, Jérôme Eeckhoute, Gilles Salbert
Chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII/NR2F2) is an orphan member of the nuclear receptor family of transcription factors whose activities are modulated upon binding of small molecules into an hydrophobic ligand-binding pocket (LBP). Although the LBP of COUP-TFII is filled with aromatic amino-acid side chains, alternative modes of ligand binding could potentially lead to regulation of the orphan receptor. Here, we screened a synthetic and natural compound library in a yeast one-hybrid assay and identified 4-methoxynaphthol as an inhibitor of COUP-TFII...
January 13, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28053540/a-novel-synthetic-asiatic-acid-derivative-induces-apoptosis-and-inhibits-proliferation-and-mobility-of-gastric-cancer-cells-by-suppressing-stat3-signaling-pathway
#4
Gang Wang, Yue Jing, Lingsen Cao, Changchang Gong, Zhunan Gong, Xiangrong Cao
Activation of the transcription factor, signal transducers and activators of transcription 3 (STAT3), has been linked to the proliferation and migration of a variety of human cancer cells. These actions occur via the upregulation or downregulation of cell survival and tumor suppressor genes, respectively. Importantly, agents that can suppress STAT3 activation have the potential for use in the prevention and treatment of various cancers. In this study, an Asiatic acid (AA) derivative, N-(2α,3β,23-acetoxyurs-12-en-28-oyl)-l-proline methyl ester (AA-PMe), is reported to dose dependently suppress constitutive STAT3 activation in gastric cancer cells...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28052257/a-fully-synthetic-transcriptional-platform-for-a-multicellular-eukaryote
#5
Justin Crocker, Albert Tsai, David L Stern
Regions of genomic DNA called enhancers encode binding sites for transcription factor proteins. Binding of activators and repressors increase and reduce transcription, respectively, but it is not understood how combinations of activators and repressors generate precise patterns of transcription during development. Here, we explore this problem using a fully synthetic transcriptional platform in Drosophila consisting of engineered transcription factor gradients and artificial enhancers. We found that binding sites for a transcription factor that makes DNA accessible are required together with binding sites for transcriptional activators to produce a functional enhancer...
January 3, 2017: Cell Reports
https://www.readbyqxmd.com/read/28049853/genetic-stability-of-genome-scale-deoptimized-rna-virus-vaccine-candidates-under-selective-pressure
#6
Cyril Le Nouën, Thomas McCarty, Michael Brown, Melissa Laird Smith, Roberto Lleras, Michael A Dolan, Masfique Mehedi, Lijuan Yang, Cindy Luongo, Bo Liang, Shirin Munir, Joshua M DiNapoli, Steffen Mueller, Eckard Wimmer, Peter L Collins, Ursula J Buchholz
Recoding viral genomes by numerous synonymous but suboptimal substitutions provides live attenuated vaccine candidates. These vaccine candidates should have a low risk of deattenuation because of the many changes involved. However, their genetic stability under selective pressure is largely unknown. We evaluated phenotypic reversion of deoptimized human respiratory syncytial virus (RSV) vaccine candidates in the context of strong selective pressure. Codon pair deoptimized (CPD) versions of RSV were attenuated and temperature-sensitive...
January 3, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28042023/diverse-pathways-of-epithelial-mesenchymal-transition-related-with-cancer-progression-and-metastasis-and-potential-effects-of-endocrine-disrupting-chemicals-on-epithelial-mesenchymal-transition-process
#7
Hae-Miru Lee, Kyung-A Hwang, Kyung-Chul Choi
Endocrine disrupting chemicals (EDCs) are natural or synthetic compounds that interfere with normal functions of natural hormones in the body, leading to a disruption of the endocrine system. Specifically, EDCs have the potential to cause formation of several hormone-dependent cancers, including breast, ovarian, and prostate cancers. Epithelial mesenchymal transition (EMT) process by which epithelial cells lose their cell polarity and cell-cell adhesion and acquire mesenchymal phenotype is closely associated with malignant transformation and the initiation of cancer metastasis...
December 29, 2016: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28036392/a-differentiation-transcription-factor-establishes-muscle-specific-proteostasis-in-caenorhabditis-elegans
#8
Yael Bar-Lavan, Netta Shemesh, Shiran Dror, Rivka Ofir, Esti Yeger-Lotem, Anat Ben-Zvi
Safeguarding the proteome is central to the health of the cell. In multi-cellular organisms, the composition of the proteome, and by extension, protein-folding requirements, varies between cells. In agreement, chaperone network composition differs between tissues. Here, we ask how chaperone expression is regulated in a cell type-specific manner and whether cellular differentiation affects chaperone expression. Our bioinformatics analyses show that the myogenic transcription factor HLH-1 (MyoD) can bind to the promoters of chaperone genes expressed or required for the folding of muscle proteins...
December 2016: PLoS Genetics
https://www.readbyqxmd.com/read/28036025/transcriptional-regulation-and-transport-of-terpenoid-indole-alkaloid-in-catharanthus-roseus-exploration-of-new-research-directions
#9
REVIEW
Jiaqi Liu, Junjun Cai, Rui Wang, Shihai Yang
As one of the model medicinal plants for exploration of biochemical pathways and molecular biological questions on complex metabolic pathways, Catharanthus roseus synthesizes more than 100 terpenoid indole alkaloids (TIAs) used for clinical treatment of various diseases and for new drug discovery. Given that extensive studies have revealed the major metabolic pathways and the spatial-temporal biosynthesis of TIA in C. roseus plant, little is known about subcellular and inter-cellular trafficking or long-distance transport of TIA end products or intermediates, as well as their regulation...
December 28, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28012646/myocardin-a-novel-player-in-atherosclerosis
#10
REVIEW
Xiao-Dan Xia, Zhen Zhou, Xiao-Hua Yu, Xi-Long Zheng, Chao-Ke Tang
Myocardin (MYOCD) the most important coactivator of serum response factor (SRF), plays a critical role specifically in the development of cardiac myocytes and vascular smooth muscle cells (VSMCs). Binding of Myocardin to the SRF on the CArG box-containing target genes can transcriptionally activate a variety of downstream muscle-specific genes, such as Sm22α, Acta2, Myh11, and several other signaling pathways. Myocardin expression represents a contractile and differentiated SMC phenotype. Loss of Myocardin, however, represents a synthetic and dedifferentiated phenotype, a hallmark in atherosclerosis...
December 1, 2016: Atherosclerosis
https://www.readbyqxmd.com/read/27999774/hyal-2-wwox-smad4-signaling-in-cell-death-and-anticancer-response
#11
REVIEW
Li-Jin Hsu, Ming-Fu Chiang, Chun-I Sze, Wan-Pei Su, Ye Vone Yap, I-Ting Lee, Hsiang-Ling Kuo, Nan-Shan Chang
Hyaluronidase HYAL-2 is a membrane-anchored protein and also localizes, in part, in the lysosome. Recent study from animal models revealed that both HYAL-1 and HYAL-2 are essential for the metabolism of hyaluronan (HA). Hyal-2 deficiency is associated with chronic thrombotic microangiopathy with hemolytic anemia in mice due to over accumulation of high molecular size HA. HYAL-2 is essential for platelet generation. Membrane HYAL-2 degrades HA bound by co-receptor CD44. Also, in a non-canonical signal pathway, HYAL-2 serves as a receptor for transforming growth factor beta (TGF-β) to signal with downstream tumor suppressors WWOX and SMAD4 to control gene transcription...
2016: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/27996095/biological-and-pharmacological-evaluation-of-dimethoxycurcumin-a-metabolically-stable-curcumin-analogue-with-a-promising-therapeutic-potential
#12
REVIEW
Manouchehr Teymouri, Nastaran Barati, Matteo Pirro, Amirhosein Sahebkar
Dimethoxycurcumin (DiMC) is a synthetic analogue of curcumin with superior inter-related pro-oxidant and anti-cancer activity, and metabolic stability. Numerous studies have shown that DiMC reserves the biologically beneficial features, including anti-inflammatory, anti-carcinogenic and cytoprotective properties, almost to the same extent as curcumin exhibits. DiMC lacks the phenolic-OH groups as opposed to curcumin, dimethoxycurcumin, and bis-demethoxycurcumin that all vary in the number of methoxy groups per molecule, and has drawn the attentions of researchers who attempted to discover the structure-activity relationship (SAR) of curcumin...
December 20, 2016: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/27988459/suppression-of-lps-induced-nf-%C3%AE%C2%BAb-activity-in-macrophages-by-the-synthetic-aurone-z-2-5-hydroxymethyl-furan-2-yl-methylene-benzofuran-3-2h-one
#13
Hyo S Park, David E Nelson, Zachary E Taylor, James B Hayes, Kirsten D Cunningham, Brock A Arivett, Rajarshi Ghosh, Larissa C Wolf, Kimberley M Taylor, Mary B Farone, Scott T Handy, Anthony L Farone
Suppressing cytokine responses has frequently been shown to have promising therapeutic effects for many chronic inflammatory and autoimmune diseases. However, the severe side effects associated with the long-term use of current treatments, such as allergic reactions and increased risk of stroke, have focused attention towards the targeting of intracellular signaling mechanisms, such as NF-κB, that regulate inflammation. We synthesized a series of non-natural aurone derivatives and investigated their ability to suppress pro-inflammatory signaling in human monocyte (THP-1) and murine macrophage-like (RAW 267...
February 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/27982133/identifying-ultrasensitive-hgf-dose-response-functions-in-a-3d-mammalian-system-for-synthetic-morphogenesis
#14
Vivek Raj Senthivel, Marc Sturrock, Gabriel Piedrafita, Mark Isalan
Nonlinear responses to signals are widespread natural phenomena that affect various cellular processes. Nonlinearity can be a desirable characteristic for engineering living organisms because it can lead to more switch-like responses, similar to those underlying the wiring in electronics. Steeper functions are described as ultrasensitive, and can be applied in synthetic biology by using various techniques including receptor decoys, multiple co-operative binding sites, and sequential positive feedbacks. Here, we explore the inherent non-linearity of a biological signaling system to identify functions that can potentially be exploited using cell genome engineering...
December 16, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27982027/engineering-orthogonal-dual-transcription-factors-for-multi-input-synthetic-promoters
#15
Andreas K Brödel, Alfonso Jaramillo, Mark Isalan
Synthetic biology has seen an explosive growth in the capability of engineering artificial gene circuits from transcription factors (TFs), particularly in bacteria. However, most artificial networks still employ the same core set of TFs (for example LacI, TetR and cI). The TFs mostly function via repression and it is difficult to integrate multiple inputs in promoter logic. Here we present to our knowledge the first set of dual activator-repressor switches for orthogonal logic gates, based on bacteriophage λ cI variants and multi-input promoter architectures...
December 16, 2016: Nature Communications
https://www.readbyqxmd.com/read/27981389/pro-differentiating-effects-of-a-synthetic-flavagline-on-human-teratocarcinomal-cancer-stem-like-cells
#16
Fathi Emhemmed, Sarah Ali Azouaou, Qian Zhao, Aline Appert-Collin, Amar Bennasroune, Valérie B Schini-Kerth, Christian D Muller, Laurent Désaubry, Guy Fuhrmann
As initiators of the carcinogenic process, cancer stem cells (CSCs) are considered as new targets for anti-cancer therapies. However, these cells are hidden in the cancer bulk and remain relatively insensitive to chemotherapy, which targets their proliferative capacities. Alternatively, growing evidences have pointed out that a differentiation therapy could adversely affect these cells, which consequently should lose their self-renewal properties and become less aggressive. In order to evaluate the differentiation potential of an emerging class of anti-cancer drugs, we used the poorly differentiated teratocarcinomal cell as a model of Oct4-expressing CSC and determined the molecular mechanisms induced by the highly active flavagline FL3...
December 15, 2016: Cell Biology and Toxicology
https://www.readbyqxmd.com/read/27978620/reprogramming-the-transcriptional-response-to-hypoxia-with-a-chromosomally-encoded-cyclic-peptide-hif-1-inhibitor
#17
Ishna N Mistry, Ali Tavassoli
The cellular response to hypoxia is orchestrated by HIF-1, a heterodimeric transcription factor composed of an α and a β subunit that enables cell survival under low oxygen conditions by altering the transcription of over 300 genes. There is significant evidence that inhibition of HIF-1 would be beneficial for cancer therapy. We recently reported a cyclic hexapeptide that inhibits the HIF-1α/HIF-1β protein-protein interaction in vitro and prevents HIF-1-mediated hypoxia-response signaling in cells. This cyclic peptide was identified from a library of 3...
November 23, 2016: ACS Synthetic Biology
https://www.readbyqxmd.com/read/27975083/microrna-based-screens-for-synthetic-lethal-interactions-with-c-myc
#18
Youjun Li, Yahui Zhu, Edward V Prochownik
microRNAs (miRs) are small, non-coding RNAs, which play crucial roles in the development and progression of human cancer. Given that miRs are stable, easy to synthetize and readily introduced into cells, they have been viewed as having potential therapeutic benefit in cancer. c-Myc (Myc) is one of the most commonly deregulated oncogenic transcription factors and has important roles in the pathogenesis of cancer, thus making it an important, albeit elusive therapeutic target. Here we review the miRs that have been identified as being both positive and negative targets for Myc and how these participate in the complex phenotypes that arise as a result of Myc-driven transformation...
2016: RNA & Disease
https://www.readbyqxmd.com/read/27966721/integrated-discovery-of-foxo1-dna-stabilizers-from-marine-natural-products-to-restore-chemosensitivity-to-anti-egfr-based-therapy-for-metastatic-lung-cancer
#19
Yingjia Sun, Xinghao Ai, Jingwen Hou, Xiangyun Ye, Ruijun Liu, Shengping Shen, Ziming Li, Shun Lu
The transcription factor forkhead box O1 (FOXO1) negatively regulates activated EGFR signaling by turning on the gene expression of tumor suppressor Kruppel-like factor 6. Here, we propose that the chemosensitivity to anti-EGFR-based lung cancer therapy can be restored by stabilization of the FOXO1-DNA complex architecture using small-molecule marine natural medicines. A synthetic protocol that integrates computational ligand-protein-DNA binding analysis and an experimental fluorescence binding assay was applied against a large library of structurally diverse, drug-like marine natural products to discover novel stabilizers of DNA-bound FOXO1 conformation...
December 14, 2016: Molecular BioSystems
https://www.readbyqxmd.com/read/27959409/galectin-3-inhibition-ameliorates-hypoxia-induced-pulmonary-artery-hypertension
#20
Mingwen Hao, Miaomiao Li, Wenjun Li
Galectin-3 (Gal-3) is a β-galactoside-binding lectin, which is important in inflammation, fibrosis and heart failure. The present study aimed to investigate the role and mechanism of Gal-3 in hypoxia-induced pulmonary arterial hypertension (PAH). Male C57BL/6J and Gal‑3‑/‑ mice were exposed to hypoxia, then the right ventricular systolic pressure (RVSP) and Fulton's index were measured, and Gal‑3 mRNA and protein expression in the pulmonary arteries was analyzed by reverse transcription‑quantitative polymerase chain reaction and western blotting...
January 2017: Molecular Medicine Reports
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