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https://www.readbyqxmd.com/read/28063003/effect-of-poly-l-arginine-in-inhibiting-scrapie-prion-protein-of-cultured-cells
#1
Muhammad Waqas, Hye-Mi Lee, Jeeyoung Kim, Glenn Telling, Jin-Ki Kim, Dae-Hwan Kim, Chongsuk Ryou
Biological effect of poly-L-arginine (PLR), the linear homopolymer comprised of L-arginine, was investigated to determine the activity of suppressing prions. PLR decreased the level of scrapie prion protein (PrP(Sc)) in cultured cells permanently infected with prions in a concentration-dependent manner. The PrP(Sc) inhibition efficacy of PLR was greater than that of another prion-suppressant poly-L-lysine (PLK) in a molecular mass-dependent fashion. The effective concentration of PLR to inhibit prions was achieved safely below the cytotoxic concentrations, and overall cytotoxicity of PLR was similar to that of PLK...
January 7, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28061448/targeting-basal-like-breast-tumors-with-bromodomain-and-extraterminal-domain-bet-and-polo-like-kinase-inhibitors
#2
Cristina Nieto-Jiménez, Ana Alcaraz-Sanabria, Javier Pérez-Peña, Verónica Corrales-Sánchez, Gemma Serrano-Heras, Eva M Galán-Moya, Leticia Serrano-Oviedo, Juan Carlos Montero, Miguel Burgos, Juan Llopis, Atanasio Pandiella, Alberto Ocaña
Metastatic triple negative breast cancer (TNBC) is an incurable disease with limited therapeutic options, and no targeted therapies available. Triple negative tumors and the basal-like genomic subtype, are both characterized by a high proliferation rate and an increase in cell division. In this context, protein kinases involved in the mitotic formation have a relevant role in this tumor subtype. Recently, Bromodomain and extraterminal domain (BET) inhibitors have shown to be active in this disease by modulating the expression of several transcription factors...
January 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/27987384/salmonella-typhimurium-ptsj-is-a-novel-mocr-like-transcriptional-repressor-involved-in-regulating-the-vitamin-b6-salvage-pathway
#3
Angela Tramonti, Teresa Milano, Caterina Nardella, Martino L di Salvo, Stefano Pascarella, Roberto Contestabile
The vitamin B6 salvage pathway, involving pyridoxine 5'-phosphate oxidase (PNPOx) and pyridoxal kinase (PLK), recycles B6 vitamers from nutrients and protein turnover to produce pyridoxal 5'-phosphate (PLP), the catalytically active form of the vitamin. Regulation of this pathway, widespread in living organisms including humans and many bacteria, is very important to vitamin B6 homeostasis but poorly understood. Although some information is available on the enzymatic regulation of PNPOx and PLK, little is known on their regulation at the transcriptional level...
December 17, 2016: FEBS Journal
https://www.readbyqxmd.com/read/27967123/head-on-collision-of-dust-acoustic-solitons-in-a-nonextensive-plasma-with-variable-size-dust-grains-of-arbitrary-charge
#4
E E Behery
The head-on collision of two dust acoustic solitons (DASs) in a nonextensive plasma with positive or negative dust grains fluid including the effect of dust size distribution (DSD) is studied. The phase shifts for the two solitons due to the collision are derived by applying the extended Poincaré-Lighthill-Kuo (PLK) method. The influences of the power law DSD and the nonextensivity of plasma particles on the characteristic properties of the head-on collision of DASs are analyzed. It is found that the phase shifts can vanish, only for the case of positive dust grains, for certain values and ranges of the dust grain radius and the entropic index of ions (q_{i})...
November 2016: Physical Review. E
https://www.readbyqxmd.com/read/27935233/kinetic-analysis-of-de-novo-centriole-assembly-in-heat-shocked-mammalian-cells
#5
In Keol Baek, Yeun Kyu Jang, Tae H Lee, JooHun Lee
Mammalian cells are capable of de novo centriole formation after the removal of existing centrioles. This suggests that de novo centriole assembly is repressed in normally duplicating cells to maintain a constant number of centrioles in the cells. However, neither the mechanism of de novo centriole assembly nor that of its hypothesized repression is understood due to the lack of an experimental system. We found that the heat shock (HS; 42°C, 2 h) of mouse embryonic fibroblasts caused the separation of centriole pairs, a transient increase in polo-like kinase (Plk) 4 expression, and the formation of a complex containing γ-tubulin, pericentrin, HS protein (Hsp) 90, and Plk4, in approximately half of the cells...
December 9, 2016: Cytoskeleton
https://www.readbyqxmd.com/read/27906199/microduplication-of-the-arid1a-gene-causes-intellectual-disability-with-recognizable-syndromic-features
#6
Marie Bidart, Michèle El Atifi, Sarra Miladi, John Rendu, Véronique Satre, Pierre F Ray, Caroline Bosson, Françoise Devillard, Daphné Lehalle, Valérie Malan, Jeanne Amiel, Maria Antonietta Mencarelli, Margherita Baldassarri, Alessandra Renieri, Jill Clayton-Smith, Gaëlle Vieville, Julien Thevenon, Florence Amblard, François Berger, Pierre-Simon Jouk, Charles Coutton
PURPOSE: To determine whether duplication of the ARID1A gene is responsible for a new recognizable syndrome. METHODS: We describe four patients with a 1p36.11 microduplication involving ARID1A as identified by array-comparative genomic hybridization . We performed comparative transcriptomic analysis of patient-derived fibroblasts using RNA sequencing and evaluated the impact of ARID1A duplication on the cell cycle using fluorescence-activated cell sorting. Functional relationships between differentially expressed genes were investigated with ingenuity pathway analysis (IPA)...
December 1, 2016: Genetics in Medicine: Official Journal of the American College of Medical Genetics
https://www.readbyqxmd.com/read/27872092/plk4-promotes-cancer-invasion-and-metastasis-through-arp2-3-complex-regulation-of-the-actin-cytoskeleton
#7
Karineh Kazazian, Christopher Go, Hannah Wu, Olga Brashavitskaya, Roland Xu, James W Dennis, Anne-Claude Gingras, Carol J Swallow
The polo family serine threonine kinase Plk4 has been proposed as a therapeutic target in advanced cancers based on increased expression in primary human cancers, facilitation of tumor growth in murine xenograft models, and centrosomal amplification induced by its overexpression. However, both the causal link between these phenomena and the feasibility of selective Plk4 inhibition remain unclear. Here we characterize Plk4-dependent cancer cell migration and invasion as well as local invasion and metastasis of cancer xenografts...
January 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/27733867/probing-unnatural-amino-acid-integration-into-enhanced-green-fluorescent-protein-by-genetic-code-expansion-with-a-high-throughput-screening-platform
#8
Georg Wandrey, Joel Wurzel, Kyra Hoffmann, Tobias Ladner, Jochen Büchs, Lorenz Meinel, Tessa Lühmann
BACKGROUND: Genetic code expansion has developed into an elegant tool to incorporate unnatural amino acids (uAA) at predefined sites in the protein backbone in response to an amber codon. However, recombinant production and yield of uAA comprising proteins are challenged due to the additional translation machinery required for uAA incorporation. RESULTS: We developed a microtiter plate-based high-throughput monitoring system (HTMS) to study and optimize uAA integration in the model protein enhanced green fluorescence protein (eGFP)...
2016: Journal of Biological Engineering
https://www.readbyqxmd.com/read/27720619/a-surveillance-system-ensures-crossover-formation-in-c-%C3%A2-elegans
#9
Tyler S Machovina, Rana Mainpal, Anahita Daryabeigi, Olivia McGovern, Dimitra Paouneskou, Sara Labella, Monique Zetka, Verena Jantsch, Judith L Yanowitz
Crossover (CO) recombination creates a physical connection between homologs that promotes their proper segregation at meiosis I (MI). Failure to realize an obligate CO causes homologs to attach independently to the MI spindle and separate randomly, leading to nondisjunction. However, mechanisms that determine whether homolog pairs have received crossovers remain mysterious. Here we describe a surveillance system in C. elegans that monitors recombination intermediates and couples their formation to meiotic progression...
November 7, 2016: Current Biology: CB
https://www.readbyqxmd.com/read/27699933/effect-of-akt3-expression-on-myc-and-caspase-8-dependent-apoptosis-caused-by-polo-like-kinase-inhibitors-in-hct-116-cells
#10
Yuma Nonomiya, Kohji Noguchi, Noritaka Tanaka, Takahiro Kasagaki, Kazuhiro Katayama, Yoshikazu Sugimoto
Polo-like kinase (PLK) is a cell-cycle regulator that is overexpressed in several cancer cell types. Polo-like kinase is considered a novel target for cancer therapies, and several PLK inhibitors (PLKis), including BI 2536, BI 6727, and GSK461364, have been developed. In this study, we established five BI 2536-resistant cell lines from human colorectal cancer HCT 116 cells, to explore the resistance mechanism and identify predictable biomarkers of PLKis. We showed that PLKi-induced caspase-8 activation was attenuated in the BI 2536-resistant cell lines...
December 2016: Cancer Science
https://www.readbyqxmd.com/read/27632389/deregulation-of-vital-mitotic-kinase-phosphatase-signaling-in-hematopoietic-stem-progenitor-compartment-leads-to-cellular-catastrophe-in-experimental-aplastic-anemia
#11
Ritam Chatterjee, Sukalpa Chattopadhyay, Sujata Law
Aplastic anemia, the paradigm of bone marrow failure, is characterized by pancytopenic peripheral blood and hypoplastic bone marrow. Among various etiologies, inappropriate use of DNA alkylating drugs like cyclophosphamide and busulfan often causes the manifestation of the dreadful disease. Cell cycle impairment in marrow hematopoietic stem/progenitor compartment together with cellular apoptosis has been recognized as culpable factors behind aplastic pathophysiologies. However, the intricate molecular mechanisms remain unrevealed till date...
November 2016: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/27608133/a-systems-biology-approach-for-elucidating-the-interaction-of-curcumin-with-fanconi-anemia-fanc-g-protein-and-the-key-disease-targets-of-leukemia
#12
David Mahato, Dipayan Samanta, Sudit S Mukhopadhyay, R Navanietha Krishnaraj
Fanconi anemia (FA) is an autosomal recessive disorder with a high risk of malignancies including acute myeloid leukemia and squamous cell carcinoma. There is a constant search out of new potential therapeutic molecule to combat this disorder. In most cases, patients with FA develop haematological malignancies with acute myeloid leukemia and acute lymphoblastic leukemia. Identifying drugs which can efficiently block the pathways of both these disorders can be an ideal and novel strategy to treat FA. The curcumin, a natural compound obtained from turmeric is an interesting therapeutic molecule as it has been reported in the literature to combat both FA as well as leukemia...
September 8, 2016: Journal of Receptor and Signal Transduction Research
https://www.readbyqxmd.com/read/27592392/identification-of-acylthiourea-derivatives-as-potent-plk1-pbd-inhibitors
#13
Taikangxiang Yun, Tan Qin, Ying Liu, Luhua Lai
Thiourea derivatives have drawn much attention for their latent capacities of biological activities. In this study, we designed acylthiourea compounds as polo-like kinase 1 (Plk1) polo-box domain (PBD) inhibitors. A series of acylthiourea derivatives without pan assay interference structure (PAINS) were synthesized. Four compounds with halogen substituents exhibited binding affinities to Plk1 PBD in low micromole range. The most potent compound (3v) showed selectivity over other subtypes of Plk PBDs and inhibited the kinase activity of full-length Plk1...
November 29, 2016: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27591191/polo-like-kinase-phosphorylation-determines-caenorhabditis-elegans-centrosome-size-and-density-by-biasing-spd-5-toward-an-assembly-competent-conformation
#14
Oliver Wueseke, David Zwicker, Anne Schwager, Yao Liang Wong, Karen Oegema, Frank Jülicher, Anthony A Hyman, Jeffrey B Woodruff
Centrosomes are major microtubule-organizing centers composed of centrioles surrounded by an extensive proteinacious layer called the pericentriolar material (PCM). In Caenorhabditis elegans embryos, the mitotic PCM expands by Polo-like kinase 1 (PLK-1) phosphorylation-accelerated assembly of SPD-5 molecules into supramolecular scaffolds. However, how PLK-1 phosphorylation regulates SPD-5 assembly is not known. We found that a mutant version of SPD-5 that is insensitive to PLK-1 phosphorylation (SPD-5(4A)) could localize to PCM but was unable to rescue the reduction in PCM size and density when wild-type SPD-5 levels were decreased...
October 15, 2016: Biology Open
https://www.readbyqxmd.com/read/27579920/interactions-of-prototype-foamy-virus-capsids-with-host-cell-polo-like-kinases-are-important-for-efficient-viral-dna-integration
#15
Irena Zurnic, Sylvia Hütter, Ute Rzeha, Nicole Stanke, Juliane Reh, Erik Müllers, Martin V Hamann, Tobias Kern, Gesche K Gerresheim, Fabian Lindel, Erik Serrao, Paul Lesbats, Alan N Engelman, Peter Cherepanov, Dirk Lindemann
Unlike for other retroviruses, only a few host cell factors that aid the replication of foamy viruses (FVs) via interaction with viral structural components are known. Using a yeast-two-hybrid (Y2H) screen with prototype FV (PFV) Gag protein as bait we identified human polo-like kinase 2 (hPLK2), a member of cell cycle regulatory kinases, as a new interactor of PFV capsids. Further Y2H studies confirmed interaction of PFV Gag with several PLKs of both human and rat origin. A consensus Ser-Thr/Ser-Pro (S-T/S-P) motif in Gag, which is conserved among primate FVs and phosphorylated in PFV virions, was essential for recognition by PLKs...
August 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27565373/reduced-kinase-activity-of-polo-kinase-cdc5-affects-chromosome-stability-and-dna-damage-response-in-s-cerevisiae
#16
Chetan C Rawal, Sara Riccardo, Chiara Pesenti, Matteo Ferrari, Federica Marini, Achille Pellicioli
Polo-like kinases (PLKs) control several aspects of eukaryotic cell division and DNA damage response. Remarkably, PLKs are overexpressed in several types of cancer, being therefore a marker of bad prognosis. As such, specific PLK kinase activity inhibitors are already used in clinical trials and the regulation of PLK activation is a relevant topic of cancer research. Phosphorylation of threonine residues in the T-loop of the kinase domain is pivotal for PLKs activation. Here, we show that T238A substitution in the T-loop reduces the kinase activity of Cdc5, the only PLK in Saccharomyces cerevisiae, with minor effect on cell growth in unperturbed conditions...
November 2016: Cell Cycle
https://www.readbyqxmd.com/read/27503460/novel-antibodies-to-phosphorylated-%C3%AE-synuclein-serine-129-and-nfl-serine-473-demonstrate-the-close-molecular-homology-of-these-epitopes
#17
Nicola J Rutherford, Mieu Brooks, Benoit I Giasson
Pathological inclusions containing aggregated, highly phosphorylated (at serine129) α-synuclein (αS pSer129) are characteristic of a group of neurodegenerative diseases termed synucleinopathies. Antibodies to the pSer129 epitope can be highly sensitive in detecting αS inclusions in human tissue and experimental models of synucleinopathies. However, the generation of extensively specific pSer129 antibodies has been problematic, in some cases leading to the misinterpretation of αS inclusion pathology. One common issue is cross-reactivity to the low molecular mass neurofilament subunit (NFL) phosphorylated at Ser473...
2016: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/27358555/flavokawain-derivative-fls-induced-g2-m-arrest-and-apoptosis-on-breast-cancer-mcf-7-cell-line
#18
Norlaily Mohd Ali, M Nadeem Akhtar, Huynh Ky, Kian Lam Lim, Nadiah Abu, Seema Zareen, Wan Yong Ho, Han Kiat Alan-Ong, Sheau Wei Tan, Noorjahan Banu Alitheen, Jamil Bin Ismail, Swee Keong Yeap, Tunku Kamarul
Known as naturally occurring biologically active compounds, flavokawain A and B are the leading chalcones that possess anticancer properties. Another flavokawain derivative, (E)-1-(2'-Hydroxy-4',6'-dimethoxyphenyl)-3-(4-methylthio)phenyl)prop-2-ene-1-one (FLS) was characterized with (1)H-nuclear magnetic resonance, electron-impact mas spectrometry, infrared spectroscopy, and ultraviolet ((1)H NMR, EI-MS, IR, and UV) spectroscopic techniques. FLS cytotoxic efficacy against human cancer cells (MCF-7, MDA-MB-231, and MCF-10A) resulted in the reduction of IC50 values in a time- and dose-dependent mode with high specificity on MCF-7 (IC50 of 36 μM at 48 hours) against normal breast cell MCF-10A (no IC50 detected up to 180 μM at 72 hours)...
2016: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/27325700/physical-association-of-saccharomyces-cerevisiae-polo-like-kinase-cdc5-with-chromosomal-cohesin-facilitates-dna-damage-response
#19
Sujiraporn Pakchuen, Mai Ishibashi, Emi Takakusagi, Katsuhiko Shirahige, Takashi Sutani
At the onset of anaphase, a protease called separase breaks the link between sister chromatids by cleaving the cohesin subunit Scc1. This irreversible step in the cell cycle is promoted by degradation of the separase inhibitor, securin, and polo-like kinase (Plk) 1-dependent phosphorylation of the Scc1 subunit. Plk could recognize substrates through interaction between its phosphopeptide interaction domain, the polo-box domain, and a phosphorylated priming site in the substrate, which has been generated by a priming kinase beforehand...
August 12, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27325299/ligand-stimulation-of-cd95-induces-activation-of-plk3-followed-by-phosphorylation-of-caspase-8
#20
Christina Helmke, Monika Raab, Franz Rödel, Yves Matthess, Thomas Oellerich, Ranadip Mandal, Mourad Sanhaji, Henning Urlaub, Claus Rödel, Sven Becker, Klaus Strebhardt
Upon interaction of the CD95 receptor with its ligand, sequential association of the adaptor molecule FADD (MORT1), pro-forms of caspases-8/10, and the caspase-8/10 regulator c-FLIP leads to the formation of a death-inducing signaling complex. Here, we identify polo-like kinase (Plk) 3 as a new interaction partner of the death receptor CD95. The enzymatic activity of Plk3 increases following interaction of the CD95 receptor with its ligand. Knockout (KO) or knockdown of caspase-8, CD95 or FADD prevents activation of Plk3 upon CD95 stimulation, suggesting a requirement of a functional DISC for Plk3 activation...
August 2016: Cell Research
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