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https://www.readbyqxmd.com/read/29244872/the-ubiquitin-proteasome-system-is-required-for-african-swine-fever-replication
#1
Lucía Barrado-Gil, Inmaculada Galindo, Diego Martínez-Alonso, Sergio Viedma, Covadonga Alonso
Several viruses manipulate the ubiquitin-proteasome system (UPS) to initiate a productive infection. Determined viral proteins are able to change the host's ubiquitin machinery and some viruses even encode their own ubiquitinating or deubiquitinating enzymes. African swine fever virus (ASFV) encodes a gene homologous to the E2 ubiquitin conjugating (UBC) enzyme. The viral ubiquitin-conjugating enzyme (UBCv1) is expressed throughout ASFV infection and accumulates at late times post infection. UBCv is also present in the viral particle suggesting that the ubiquitin-proteasome pathway could play an important role at early ASFV infection...
2017: PloS One
https://www.readbyqxmd.com/read/29244866/molecular-dynamics-simulations-of-the-glucocorticoid-receptor-dna-binding-domain-suggest-a-role-of-the-lever-arm-mobility-in-transcriptional-output
#2
Lautaro Damián Álvarez, Diego Martín Presman, Adalí Pecci
One of the first and essential steps in gene expression regulation involves the recruitment of transcription factors (TFs) to specific response elements located at enhancers and/or promoters of targeted genes. These DNA elements have a certain variability in both sequence and length, which may affect the final transcriptional output. The molecular mechanisms in which TFs integrate the subtle differences within specific recognition sequences to offer different transcriptional responses is still largely unknown...
2017: PloS One
https://www.readbyqxmd.com/read/29244486/going-vertical-to-improve-the-accuracy-of-atomic-force-microscopy-based-single-molecule-force-spectroscopy
#3
Robert Walder, William J Van Patten, Ayush Adhikari, Thomas T Perkins
Single-molecule force spectroscopy (SMFS) is a powerful technique to characterize the energy landscape of individual proteins, the mechanical properties of nucleic acids, and the strength of receptor-ligand interactions. Atomic-force-microscopy (AFM)-based SMFS benefits from ongoing progress in improving the precision and stability of cantilevers and the AFM itself. Underappreciated is that the accuracy of such AFM studies remains hindered by inadvertently stretching molecules at an angle while measuring only the vertical component of the force and extension, degrading both measurements...
December 15, 2017: ACS Nano
https://www.readbyqxmd.com/read/29244158/znf830-mediates-cancer-chemoresistance-through-promoting-homologous-recombination-repair
#4
Guo Chen, Jianxiang Chen, Yiting Qiao, Yaru Shi, Wei Liu, Qi Zeng, Hui Xie, Xiaorui Shi, Youwei Sun, Xu Liu, Tongyu Li, Liqian Zhou, Jianqin Wan, Tian Xie, Hangxiang Wang, Fu Wang
Homologous recombination (HR), which mediates the repair of DNA double-strand breaks (DSB), is crucial for maintaining genomic integrity and enhancing survival in response to chemotherapy and radiotherapy in human cancers. However, the mechanisms of HR repair in treatment resistance for the improvement of cancer therapy remains unclear. Here, we report that the zinc finger protein 830 (ZNF830) promotes HR repair and the survival of cancer cells in response to DNA damage. Mechanistically, ZNF830 directly participates in DNA end resection via interacting with CtIP and regulating CtIP recruitment to DNA damage sites...
December 13, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29243757/musa-paradisiaca-inflorescence-induces-human-colon-cancer-cell-death-by-modulating-cascades-of-transcriptional-events
#5
Arun K B, Aravind Madhavan, Reshmitha T R, Sithara Thomas, P Nisha
Colorectal cancer (CRC) is one of the leading causes of cancer death, and diet plays an important role in the etiology of CRC. Traditional medical practitioners in many South Asian countries use plantain inflorescence to treat various gastro-intestinal ailments. The aim of the present study was to investigate the anticancer effects of extracts of inflorescence of Musa paradisiaca against HT29 human colon cancer cells and elucidate the mechanism of these effects by studying the modulation of cascades of transcriptional events...
December 15, 2017: Food & Function
https://www.readbyqxmd.com/read/29243081/a-novel-dmapp-responding-genetic-circuit-sensor-for-high-throughput-screening-and-evolving-isoprene-synthase
#6
Chun-Li Liu, Jing-Yi Cai, Hao-Ran Bi, Tian-Wei Tan
High-throughput screening is a popular tool for collating biological data which would otherwise require the use of excessive resources. In this study, an artificial genetic circuit sensor responding to dimethylallyl diphosphate (DMAPP) was constructed based on a modified L-arabinose operon for high-throughput screening and isoprene synthase (ispS) evolution in Escherichia coli (E. coli). As a first step, the DNA sequence of the L-arabinose ligand-binding domain (LBD) was replaced with an ispS gene to enable the AraC operon responding to DMAPP, which is the substrate of the IspS enzyme...
December 14, 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/29243047/role-of-%C3%AE-catenin-in-cisplatin-resistance-relapse-and-prognosis-of-head-and-neck-squamous-cell-carcinoma
#7
Souvick Roy, Madhabananda Kar, Shomereeta Roy, Arka Saha, Swatishree Padhi, Birendranath Banerjee
BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is one of the most common types of cancer in India with high incidence and rapid recurrence rates. Here, we aimed to investigate the role of β-catenin, a developmental pathway gene, in HNSCC therapy resistance, DNA damage response, recurrence and prognosis. METHODS: In total 80 HNSCC samples were included. Western blot, immunohistochemistry and qRT-PCR analyses were performed to assess β-catenin expression in the cut margin and tumor areas of each sample...
December 14, 2017: Cellular Oncology (Dordrecht)
https://www.readbyqxmd.com/read/29242538/nuclear-rnf2-inhibits-interferon-function-by-promoting-k33-linked-stat1-disassociation-from-dna
#8
Shuo Liu, Minghong Jiang, Wendie Wang, Wei Liu, Xiaoqi Song, Zhongfei Ma, Shikun Zhang, Lun Liu, Yin Liu, Xuetao Cao
Prolonged activation of interferon-STAT1 signaling is closely related to inflammatory autoimmune disorders, and therefore the identification of negative regulators of these pathways is important. Through high-content screening of 115 mouse RING-domain E3 ligases, we identified the E3 ubiquitin ligase RNF2 as a potent inhibitor of interferon-dependent antiviral responses. RNF2 deficiency substantially enhanced interferon-stimulated gene (ISG) expression and antiviral responses. Mechanistically, nuclear RNF2 directly bound to STAT1 after interferon stimulation and increased K33-linked polyubiquitination of the DNA-binding domain of STAT1 at position K379, in addition to promoting the disassociation of STAT1/STAT2 from DNA and consequently suppressing ISG transcription...
January 2018: Nature Immunology
https://www.readbyqxmd.com/read/29242354/moving-synergistically-acting-drug-combinations-to-the-clinic-by-comparing-sequential-versus-simultaneous-drug-administrations
#9
Saketh S Dinavahi, Mohammed A Noory, Raghavendra Gowda, Joseph J Drabick, Rogerio I Neves, Arthur Berg, Gavin P Robertson
Drug combinations acting synergistically to kill cancer cells have become increasingly important in melanoma as an approach to manage the recurrent resistant disease. AKT is a major target in this disease but its inhibitors are not effective clinically, which is a major concern. Targeting AKT in combination with WEE1 seems to have potential to make AKT based therapeutics effective clinically. Since agents targeting AKT and WEE1 have been tested individually in the clinic, the quickest way to move the drug combination to patients would be to combine them sequentially, enabling the use of existing phase-I clinical trial toxicity data...
December 14, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/29242163/changes-of-dna-topology-affect-the-global-transcription-landscape-and-allow-rapid-growth-of-a-bacillus-subtilis-lacking-carbon-catabolite-repression
#10
Daniel R Reuß, Hermann Rath, Andrea Thürmer, Martin Benda, Rolf Daniel, Uwe Völker, Ulrike Mäder, Fabian M Commichau, Jörg Stülke
Bacteria are able to prioritize preferred carbon sources from complex mixtures. This is achieved by the regulatory phenomenon of carbon catabolite repression. To allow the simultaneous utilization of multiple carbon sources and to prevent the time-consuming adaptation to each individual nutrient in biotechnological applications, mutants lacking carbon catabolite repression can be used. However, such mutants often exhibit pleiotropic growth defects. We have isolated and characterized mutations that overcome the growth defect of Bacillus subtilis ccpA mutants lacking the major regulator of catabolite repression, in particular their glutamate auxotrophy...
December 11, 2017: Metabolic Engineering
https://www.readbyqxmd.com/read/29241579/punicalagin-from-pomegranate-promotes-human-papillary-thyroid-carcinoma-bcpap-cell-death-by-triggering-atm-mediated-dna-damage-response
#11
Xin Yao, Xian Cheng, Li Zhang, Huixin Yu, Jiandong Bao, Haixia Guan, Rongrong Lu
Punicalagin (PUN), a component derived from pomegranate, is well known for its anticancer activity. Our previous work revealed that PUN induces autophagic cell death in papillary thyroid carcinoma cells. We hypothesized that PUN triggers DNA damage associated with cell death because DNA damage was reported as an inducer of autophagy. Our results showed that PUN treatment caused DNA breaks as evidenced by the significant enhancement in the phosphorylation of H2A.X. However, reactive oxygen species and DNA conformational alteration, 2 common inducing factors in DNA damage, were not involved in PUN-induced DNA damage...
November 2017: Nutrition Research
https://www.readbyqxmd.com/read/29240807/diversification-of-the-insulin-like-growth-factor-1-gene-in-mammals
#12
Peter Rotwein
Insulin-like growth factor 1 (IGF1), a small, secreted peptide growth factor, is involved in a variety of physiological and patho-physiological processes, including somatic growth, tissue repair, and metabolism of carbohydrates, proteins, and lipids. IGF1 gene expression appears to be controlled by several different signaling cascades in the few species in which it has been evaluated, with growth hormone playing a major role by activating a pathway involving the Stat5b transcription factor. Here, genes encoding IGF1 have been evaluated in 25 different mammalian species representing 15 different orders and ranging over ~180 million years of evolutionary diversification...
2017: PloS One
https://www.readbyqxmd.com/read/29239726/camp-signaling-regulates-dna-hydroxymethylation-by-augmenting-the-intracellular-labile-ferrous-iron-pool
#13
Vladimir Camarena, David W Sant, Tyler C Huff, Sushimita Mustafi, Ryan K Muir, Allegra T Aron, Christopher J Chang, Adam R Renslo, Paula Monje, Gaofeng Wang
It is widely accepted that cAMP regulates gene transcription principally by activating the protein kinase A (PKA)-targeted transcription factors. Here, we show that cAMP enhances the generation of 5-hydroxymethylcytosine (5hmC) in multiple cell types. 5hmC is converted from 5-methylcytosine (5mC) by Tet methylcytosine dioxygenases, for which Fe(II) is an essential cofactor. The promotion of 5hmC was mediated by a prompt increase of the intracellular labile Fe(II) pool (LIP). cAMP enhanced the acidification of endosomes for Fe(II) release to the LIP likely through RapGEF2...
December 14, 2017: ELife
https://www.readbyqxmd.com/read/29238994/intestinal-p-glycoprotein-inhibitors-benzoxanthone-analogues
#14
Song Wha Chae, Jaeok Lee, Jung Hyun Park, Youngjoo Kwon, Younghwa Na, Hwa Jeong Lee
OBJECTIVES: The inhibitors of P-glycoprotein (P-gp) which limits an access of exogenous compounds in the luminal membrane of the intestine have been studied to enhance the intestinal P-gp-mediated absorption of anticancer drugs. METHODS: Inhibition of the efflux pump by synthesized benzoxanthone derivatives was investigated in vitro and in vivo. MCF-7/ADR cell line was used for cytotoxicity assay and [3 H]-daunomycin (DNM) accumulation/efflux study. Eight benzoxanthone analogues were tested for their effects on DNM cytotoxicity...
December 13, 2017: Journal of Pharmacy and Pharmacology
https://www.readbyqxmd.com/read/29238267/augmented-expression-of-cardiac-ankyrin-repeat-protein-is-induced-by-pemetrexed-and-a-possible-marker-for-the-pemetrexed-resistance-in-mesothelioma-cells
#15
Yiyang Qin, Ikuo Sekine, Mengmeng Fan, Yuichi Takiguchi, Yuji Tada, Masato Shingyoji, Michiko Hanazono, Naoto Yamaguchi, Masatoshi Tagawa
Background: Pemetrexed (PEM) is an anti-cancer agent targeting DNA and RNA synthesis, and clinically in use for mesothelioma and non-small cell lung carcinoma. A mechanism of resistance to PEM is associated with elevated activities of several enzymes involved in nucleic acid metabolism. Methods: We established two kinds of PEM-resistant mesothelioma cells which did not show any increase of the relevant enzyme activities. We screened genes enhanced in the PEM-resistant cells with a microarray analysis and confirmed the expression levels with Western blot analysis...
2017: Cancer Cell International
https://www.readbyqxmd.com/read/29238067/alternative-nhej-pathway-proteins-as-components-of-mycn-oncogenic-activity-in-human-neural-crest-stem-cell-differentiation-implications-for-neuroblastoma-initiation
#16
Erika A Newman, Sahiti Chukkapalli, Daniela Bashllari, Tina T Thomas, Raelene A Van Noord, Elizabeth R Lawlor, Mark J Hoenerhoff, Anthony W Opipari, Valerie P Opipari
Neuroblastoma is a cancer of neural crest stem cell (NCSC) lineage. Signaling pathways that regulate NCSC differentiation have been implicated in neuroblastoma tumorigenesis. This is exemplified by MYCN oncogene targets that balance proliferation, differentiation, and cell death similarly in normal NCSC and in high-risk neuroblastoma. Our previous work discovered a survival mechanism by which MYCN-amplified neuroblastoma circumvents cell death by upregulating components of the error-prone non-canonical alternative nonhomologous end-joining (alt-NHEJ) DNA repair pathway...
December 13, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/29237847/a-trimeric-hiv-1-envelope-gp120-immunogen-induces-potent-and-broad-anti-v1v2-loop-antibodies-against-hiv-1-in-rabbits-and-rhesus-macaques
#17
Andrew T Jones, Venkateswarlu Chamcha, Sannula Kesavardhana, Xiaoying Shen, David Beaumont, Raksha Das, Linda S Wyatt, Celia C LaBranche, Sherry Stanfield-Oakley, Guido Ferrari, David C Montefiori, Bernard Moss, Georgia D Tomaras, Raghavan Varadarajan, Rama Rao Amara
Trimeric HIV-1 envelope (Env) immunogens are attractive due to their ability to display quaternary epitopes targeted by broadly neutralizing antibodies while obscuring unfavorable epitopes. Results from the RV144 trial highlighted the importance of vaccine induced HIV-1 Env V1V2 directed antibodies, with key regions of the V2 loop as targets for vaccine-mediated protection. We recently reported that a trimeric JRFL-gp120 immunogen, generated by inserting a N-terminal trimerization domain in the V1 loop region of a cyclically permuted gp120 (cycP-gp120), induces neutralizing activity against multiple tier-2 HIV-1 isolates in guinea pigs in a DNA prime/protein boost approach...
December 13, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29237539/cdkn2a-deficiency-promotes-adipose-tissue-browning
#18
Nabil Rabhi, Sarah Anissa Hannou, Xavier Gromada, Elisabet Salas, Xi Yao, Frédérik Oger, Charlène Carney, Isabel C Lopez-Mejia, Emmanuelle Durand, Iandry Rabearivelo, Amélie Bonnefond, Emilie Caron, Lluis Fajas, Christian Dani, Philippe Froguel, Jean-Sébastien Annicotte
OBJECTIVES: Genome-wide association studies have reported that DNA polymorphisms at the CDKN2A locus modulate fasting glucose in human and contribute to type 2 diabetes (T2D) risk. Yet the causal relationship between this gene and defective energy homeostasis remains elusive. Here we sought to understand the contribution of Cdkn2a to metabolic homeostasis. METHODS: We first analyzed glucose and energy homeostasis from Cdkn2a-deficient mice subjected to normal or high fat diets...
December 1, 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/29236713/sirt3-deficiency-does-not-affect-venous-thrombosis-or-netosis-despite-mild-elevation-of-intracellular-ros-in-platelets-and-neutrophils-in-mice
#19
Hideki Hayashi, Deya Cherpokova, Kimberly Martinod, Thilo Witsch, Siu Ling Wong, Maureen Gallant, Stephen M Cifuni, Leonard P Guarente, Denisa D Wagner
Inflammation is a common denominator in chronic diseases of aging. Yet, how inflammation fuels these diseases remains unknown. Neutrophils are the primary leukocytes involved in the early phase of innate immunity and inflammation. As part of their anti-microbial defense, neutrophils form extracellular traps (NETs) by releasing decondensed chromatin lined with cytotoxic proteins. NETs have been shown to induce tissue injury and thrombosis. Here, we demonstrated that Sirt3, a nicotinamide adenine dinucleotide (NAD+)-dependent protein deacetylase, an enzyme linked to human longevity, was expressed in mouse neutrophils and platelets...
2017: PloS One
https://www.readbyqxmd.com/read/29236325/aml1-eto-trans-activates-c-kit-expression-through-the-long-range-interaction-between-promoter-and-intronic-enhancer
#20
Ying Tian, Genjie Wang, Qingzhu Hu, Xichun Xiao, Shuxia Chen
The AML1/ETO onco-fusion protein is crucial for the genesis of t(8;21) acute myeloid leukemia (AML) and is well documented as a transcriptional repressor through dominant-negative effect. However, little is known about the transactivation mechanism of AML1/ETO. Through large cohort of patient's expression level data analysis and a series of experimental validation, we report here that AML1/ETO transactivates c-KIT expression through directly binding to and mediating the long-range interaction between the promoter and intronic enhancer regions of c-KIT...
December 13, 2017: Journal of Cellular Biochemistry
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