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https://www.readbyqxmd.com/read/28934471/a-novel-non-canonical-pip-box-mediates-parg-interaction-with-pcna
#1
Tanja Kaufmann, Irina Grishkovskaya, Anton A Polyansky, Sebastian Kostrhon, Eva Kukolj, Karin M Olek, Sebastien Herbert, Etienne Beltzung, Karl Mechtler, Thomas Peterbauer, Josef Gotzmann, Lijuan Zhang, Markus Hartl, Bojan Zagrovic, Kareem Elsayad, Kristina Djinovic-Carugo, Dea Slade
Poly(ADP-ribose) glycohydrolase (PARG) regulates cellular poly(ADP-ribose) (PAR) levels by rapidly cleaving glycosidic bonds between ADP-ribose units. PARG interacts with proliferating cell nuclear antigen (PCNA) and is strongly recruited to DNA damage sites in a PAR- and PCNA-dependent fashion. Here we identified PARG acetylation site K409 that is essential for its interaction with PCNA, its localization within replication foci and its recruitment to DNA damage sites. We found K409 to be part of a non-canonical PIP-box within the PARG disordered regulatory region...
September 19, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28723107/chemical-approaches-to-investigate-labile-peptide-and-protein-phosphorylation
#2
Anett Hauser, Martin Penkert, Christian P R Hackenberger
Protein phosphorylation is by far the most abundant and most studied post-translational modification (PTM). For a long time, phosphate monoesters of serine (pSer), threonine (pThr), and tyrosine (pTyr) have been considered as the only relevant forms of phosphorylation in organisms. Recently, several research groups have dedicated their efforts to the investigation of other, less characterized phosphoamino acids as naturally occurring PTMs. Such apparent peculiar phosphorylations include the phosphoramidates of histidine (pHis), arginine (pArg), and lysine (pLys), the phosphorothioate of cysteine (pCys), and the anhydrides of pyrophosphorylated serine (ppSer) and threonine (ppThr)...
July 19, 2017: Accounts of Chemical Research
https://www.readbyqxmd.com/read/28695524/studying-catabolism-of-protein-adp-ribosylation
#3
Luca Palazzo, Dominic I James, Ian D Waddell, Ivan Ahel
Protein ADP-ribosylation is a conserved posttranslational modification that regulates many major cellular functions, such as DNA repair, transcription, translation, signal transduction, stress response, cell division, aging, and cell death. Protein ADP-ribosyl transferases catalyze the transfer of an ADP-ribose (ADPr) group from the β-nicotinamide adenine dinucleotide (β-NAD(+)) cofactor onto a specific target protein with the subsequent release of nicotinamide. ADP-ribosylation leads to changes in protein structure, function, stability, and localization, thus defining the appropriate cellular response...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28695523/purification-of-recombinant-human-parg-and-activity-assays
#4
Jean-Christophe Amé, Éléa Héberlé, Barbara Camuzeaux, Françoise Dantzer, Valérie Schreiber
The purification of Poly(ADP-ribose) glycohydrolase (PARG) from overexpressing bacteria Escherichia coli is described here to a fast and reproducible one chromatographic step protocol. After cell lysis, GST-PARG-fusion proteins from the crude extract are affinity purified by a Glutathione 4B Sepharose chromatographic step. The PARG proteins are then freed from their GST-fusion by overnight enzymatic cleavage using the preScission protease. As described in the protocol, more than 500 μg of highly active human PARG can be obtained from 1...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28695503/cell-cycle-resolved-measurements-of-poly-adp-ribose-formation-and-dna-damage-signaling-by-quantitative-image-based-cytometry
#5
Jone Michelena, Matthias Altmeyer
Formation of poly(ADP-ribose) (PAR) marks intracellular stress signaling and is notably induced upon DNA damage. PAR polymerases (PARPs) catalyze PAR synthesis upon genotoxic stress and thereby recruit multiple proteins to damaged chromatin. PAR induction is transient and antagonized by the action of PAR glycohydrolase (PARG). Given that poly(ADP-ribosyl)ation (PARylation) is involved in genome integrity maintenance and other vital cellular functions, but also in light of the recent approval of PARP inhibitors for cancer treatments, reliable measurements of intracellular PAR formation have gained importance...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28687616/posttranscriptional-regulation-of-parg-mrna-by-hur-facilitates-dna-repair-and-resistance-to-parp-inhibitors
#6
Saswati N Chand, Mahsa Zarei, Matthew J Schiewer, Akshay R Kamath, Carmella Romeo, Shruti Lal, Joseph A Cozzitorto, Avinoam Nevler, Laura Scolaro, Eric Londin, Wei Jiang, Nicole Meisner-Kober, Michael J Pishvaian, Karen E Knudsen, Charles J Yeo, John M Pascal, Jordan M Winter, Jonathan R Brody
The majority of pancreatic ductal adenocarcinomas (PDAC) rely on the mRNA stability factor HuR (ELAV-L1) to drive cancer growth and progression. Here, we show that CRISPR-Cas9-mediated silencing of the HuR locus increases the relative sensitivity of PDAC cells to PARP inhibitors (PARPi). PDAC cells treated with PARPi stimulated translocation of HuR from the nucleus to the cytoplasm, specifically promoting stabilization of a new target, poly (ADP-ribose) glycohydrolase (PARG) mRNA, by binding a unique sequence embedded in its 3' untranslated region...
July 7, 2017: Cancer Research
https://www.readbyqxmd.com/read/28684364/polyarginine-nanocapsules-a-versatile-nanocarrier-with-potential-in-transmucosal-drug-delivery
#7
Ana Gonzalez-Paredes, Dolores Torres, María José Alonso
The objective of this work was to investigate the potential utility of nanocapsules composed of an oily core decorated with a single polyarginine (PARG), or double PARG/polyacrylic acid (PAA) layer as oral peptide delivery carrier. A step-by-step formulation optimization process was designed, which involved the study of the influence of the surfactants, oils and polymer shells (PARG of different molecular weight and PAA) on the nanocapsules physicochemical properties, peptide loading efficiency, stability in simulated intestinal fluids (SIF) and capacity to enhance the permeability of the intestinal epithelium...
July 3, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28668129/what-combined-measurements-from-structures-and-imaging-tell-us-about-dna-damage-responses
#8
Chris A Brosey, Zamal Ahmed, Susan P Lees-Miller, John A Tainer
DNA damage outcomes depend upon the efficiency and fidelity of DNA damage responses (DDRs) for different cells and damage. As such, DDRs represent tightly regulated prototypical systems for linking nanoscale biomolecular structure and assembly to the biology of genomic regulation and cell signaling. However, the dynamic and multifunctional nature of DDR assemblies can render elusive the correlation between the structures of DDR factors and specific biological disruptions to the DDR when these structures are altered...
2017: Methods in Enzymology
https://www.readbyqxmd.com/read/28525621/from-the-cover-ros-induced-store-operated-ca2-entry-coupled-to-parp-1-hyperactivation-is-independent-of-parg-activity-in-necrotic-cell-death
#9
Frances M Munoz, Fengjiao Zhang, Argel Islas-Robles, Serrine S Lau, Terrence J Monks
2,3,5-tris(Glutathion-S-yl)hydroquinone, a potent nephrotoxic and nephrocarcinogenic metabolite of benzene and hydroquinone, generates reactive oxygen species (ROS) causing DNA strand breaks and the subsequent activation of DNA repair enzymes, including poly(ADP-ribose) polymerase (PARP)-1. Under robust oxidative DNA damage, PARP-1 is hyperactivated, resulting in the depletion of NAD+ and ATP with accompanying elevations in intracellular calcium concentrations (iCa2+), and ultimately necrotic cell death. The role of Ca2+ during PARP-dependent necrotic cell death remains unclear...
August 1, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28503382/poly-adp-ribosylation-is-present-in-murine-sciatic-nerve-fibers-and-is-altered-in-a-charcot-marie-tooth-1e-neurodegenerative-model
#10
Laura I Lafon Hughes, Carlos J Romeo Cardeillac, Karina B Cal Castillo, Salomé C Vilchez Larrea, José R Sotelo Sosa, Gustavo A Folle Ungo, Silvia H Fernández Villamil, Alejandra E Kun González
BACKGROUND: Poly-ADP-ribose (PAR) is a polymer synthesized by poly-ADP-ribose polymerases (PARPs) as a postranslational protein modification and catabolized mainly by poly-ADP-ribose glycohydrolase (PARG). In spite of the existence of cytoplasmic PARPs and PARG, research has been focused on nuclear PARPs and PAR, demonstrating roles in the maintenance of chromatin architecture and the participation in DNA damage responses and transcriptional regulation. We have recently detected non-nuclear PAR structurally and functionally associated to the E-cadherin rich zonula adherens and the actin cytoskeleton of VERO epithelial cells...
2017: PeerJ
https://www.readbyqxmd.com/read/28415460/poly-arginine-graphene-quantum-dots-as-a-biocompatible-and-non-toxic-nanocomposite-layer-by-layer-electrochemical-preparation-characterization-and-non-invasive-malondialdehyde-sensory-application-in-exhaled-breath-condensate
#11
Mohammad Hasanzadeh, Fozieh Mokhtari, Nasrin Shadjou, Aziz Eftekhari, Ahad Mokhtarzadeh, Vahid Jouyban-Gharamaleki, Soltanali Mahboob
This study reports on the electropolymerization of a low toxic and biocompatible polymer with entitle poly arginine-graphene quantum dots (PARG-GQDs) as a novel strategy for surface modification of glassy carbon (GC) surface and preparation a new interface for biomedical application. The fabrication of PARG-GQDs on GCE was performed using Layer-by-layer regime. Scanning electron microscopy (SEM) was confirmed dispersion of GQDs on the surface of PARG which lead to increase of surface coverage of PARG. The redox behavior of prepared sensor was then characterized by cyclic voltammetry (CV), differential pulse voltammetry (DPV) and chronoamperometry (CHA), square wave voltammetry (SWV), linear sweep voltammetry (LSV)...
June 1, 2017: Materials Science & Engineering. C, Materials for Biological Applications
https://www.readbyqxmd.com/read/28254358/specific-killing-of-dna-damage-response-deficient-cells-with-inhibitors-of-poly-adp-ribose-glycohydrolase
#12
Polly Gravells, Emma Grant, Kate M Smith, Dominic I James, Helen E Bryant
Poly(ADP-ribosylation) of proteins following DNA damage is well studied and the use of poly(ADP-ribose) polymerase (PARP) inhibitors as therapeutic agents is an exciting prospect for the treatment of many cancers. Poly(ADP-ribose) glycohydrolase (PARG) has endo- and exoglycosidase activities which can cleave glycosidic bonds, rapidly reversing the action of PARP enzymes. Like addition of poly(ADP-ribose) (PAR) by PARP, removal of PAR by PARG is also thought to be required for repair of DNA strand breaks and for continued replication at perturbed forks...
April 2017: DNA Repair
https://www.readbyqxmd.com/read/28235590/rational-design-of-polyarginine-nanocapsules-intended-to-help-peptides-overcoming-intestinal-barriers
#13
Zhigao Niu, Erik Tedesco, Federico Benetti, Aloïse Mabondzo, Isabella Monia Montagner, Ilaria Marigo, David Gonzalez-Touceda, Sulay Tovar, Carlos Diéguez, Manuel J Santander-Ortega, María J Alonso
The aim of this work was to rationally design and characterize nanocapsules (NCs) composed of an oily core and a polyarginine (PARG) shell, intended for oral peptide delivery. The cationic polyaminoacid, PARG, and the oily core components were selected based on their penetration enhancing properties. Insulin was adopted as a model peptide to assess the performance of the NCs. After screening numerous formulation variables, including different oils and surfactants, we defined a composition consisting of oleic acid, sodium deoxycholate (SDC) and Span 80...
February 21, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28144953/the-rhce-ce-501a-allele-encodes-the-parg-antigen-rh60
#14
Erwin A Scharberg, Gabi Rink, Sabine Roth, Susanne Seyboth, Ekkehard Richter, Birgit S Gathof, Jürgen Burkhart, Peter Bugert
No abstract text is available yet for this article.
January 31, 2017: Transfusion
https://www.readbyqxmd.com/read/28069389/layer-by-layer-assembly-of-hierarchical-nanoarchitectures-to-enhance-the-systemic-performance-of-nanoparticle-albumin-bound-paclitaxel
#15
Hima Bindu Ruttala, Thiruganesh Ramasamy, Beom Soo Shin, Han-Gon Choi, Chul Soon Yong, Jong Oh Kim
Although protein-bound paclitaxel (PTX, Abraxane(®)) has been established as a standard PTX-based therapy against multiple cancers, its clinical success is limited by unfavorable pharmacokinetics, suboptimal biodistribution, and acute toxicities. In the present study, we aimed to apply the principles of a layer-by-layer (LbL) technique to improve the poor colloidal stability and pharmacokinetic pattern of nanoparticle albumin-bound paclitaxel (nab-PTX). LbL-based nab-PTX was successfully fabricated by the alternate deposition of polyarginine (pARG) and poly(ethylene glycol)-block-poly (L-aspartic acid) (PEG-b-PLD) onto an albumin conjugate...
March 15, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28034957/a-three-dimensional-parf-meshwork-assembles-through-the-nucleoid-to-mediate-plasmid-segregation
#16
Brett N McLeod, Gina E Allison-Gamble, Madhuri T Barge, Nam K Tonthat, Maria A Schumacher, Finbarr Hayes, Daniela Barillà
Genome segregation is a fundamental step in the life cycle of every cell. Most bacteria rely on dedicated DNA partition proteins to actively segregate chromosomes and low copy-number plasmids. Here, by employing super resolution microscopy, we establish that the ParF DNA partition protein of the ParA family assembles into a three-dimensional meshwork that uses the nucleoid as a scaffold and periodically shuttles between its poles. Whereas ParF specifies the territory for plasmid trafficking, the ParG partner protein dictates the tempo of ParF assembly cycles and plasmid segregation events by stimulating ParF adenosine triphosphate hydrolysis...
April 7, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28034453/dna-damage-repair-in-breast-cancer-and-its-therapeutic-implications
#17
REVIEW
Reem Ali, Emad A Rakha, Srinivasan Madhusudan, Helen E Bryant
The DNA damage response (DDR) involves the activation of numerous cellular activities that repair DNA lesions and maintain genomic integrity, and is critical in preventing tumorigenesis. Inherited or acquired mutations in specific genes involved in the DNA damage response, for example the breast cancer susceptibility genes 1/2 (BRCA1/2), phosphatase and tensin homolog (PTEN) and P53 are associated with various subtypes of breast cancer. Such changes can render breast cancer cells particularly sensitive to specific DNA damage response inhibitors, for example BRCA1/2 germline mutated cells are sensitive to poly (ADP-ribose) polymerase (PARP) inhibitors...
February 2017: Pathology
https://www.readbyqxmd.com/read/27921280/ph-responsive-triblock-copolymeric-micelles-decorated-with-a-cell-penetrating-peptide-provide-efficient-doxorubicin-delivery
#18
Khen Eng Ng, Mohd Cairul Iqbal Mohd Amin, Haliza Katas, Muhammad Wahab Amjad, Adeel Masood Butt, Prashant Kesharwani, Arun K Iyer
This study developed novel triblock pH-responsive polymeric micelles (PMs) using cholic acid-polyethyleneimine-poly-L-arginine (CA-PEI-pArg) copolymers. PEI provided pH sensitivity, while the hydrophilic cell-penetrating pArg peptide promoted cellular PM internalization. The copolymers self-assembled into PMs in aqueous solution at above the critical micelle concentration (2.98 × 10(-7) M) and encapsulated doxorubicin in the core region, with a 34.2% (w/w) entrapment efficiency. PMs showed pH-dependent swelling, increasing in size by almost sevenfold from pH 7...
December 2016: Nanoscale Research Letters
https://www.readbyqxmd.com/read/27855960/polyarginine-nanocapsules-as-a-potential-oral-peptide-delivery-carrier
#19
Giovanna Lollo, Ana Gonzalez-Paredes, Marcos Garcia-Fuentes, Pilar Calvo, Dolores Torres, Maria Jose Alonso
We have previously reported the development of novel nanocapsules made of polyarginine (PArg) specifically designed for the delivery of small anticancer drugs into cells. Our goal, in this work, has been to investigate the potential of these nanocarriers for oral delivery of peptide anticancer drugs. To reach this objective, we chose the antitumoral peptide, elisidepsin, and evaluated the characteristics of the PArg nanocapsules in terms of drug loading capacity, stability in simulated intestinal fluids, and ability to interact with the intestinal epithelium both in vitro (Caco-2 model cell line) and in vivo...
February 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/27817743/new-insights-into-the-roles-of-nad-poly-adp-ribose-metabolism-and-poly-adp-ribose-glycohydrolase
#20
REVIEW
Seiichi Tanuma, Akira Sato, Takahiro Oyama, Atsushi Yoshimori, Hideaki Abe, Fumiaki Uchiumi
Accumulating evidence has suggested the fundamental functions of NAD+-poly(ADP-ribose) metabolism in cellular and physiological processes, including energy homeostasis, signal transduction, DNA transaction, genomic stability and cell death or survival. The NAD+ biosynthesis and poly(ADP-ribose) [(ADP-R)n] turnover are tightly controlled by several key enzymes, such as nicotinamide phosphoribosyltransferase (NmPRT), nicotinamide mononucleotide adenylyltransferases (NMNATs), poly(ADP-ribose) polymerase (PARP), poly(ADP-ribose) glycohydrolase (PARG) and ADP-ribose pyrophosphorylase (ADPRPPL)...
2016: Current Protein & Peptide Science
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