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https://www.readbyqxmd.com/read/28650470/signaling-coupled-epigenomic-regulation-of-gene-expression
#1
REVIEW
R Kumar, S Deivendran, T R Santhoshkumar, M R Pillai
Inheritance of genomic information independent of the DNA sequence, the epigenetics, as well as gene transcription are profoundly shaped by serine/threonine and tyrosine signaling kinases and components of the chromatin remodeling complexes. To precisely respond to a changing external milieu, human cells efficiently translate upstream signals into post-translational modifications (PTMs) on histones and coregulators such as corepressors, coactivators, DNA-binding factors and PTM modifying enzymes. Because a protein with multiple residues for putative PTMs is expected to undergo more than one PTM in cells stimulated with growth factors, the outcome of combinational PTM codes on histones and coregulators is profoundly shaped by regulatory interplays between PTMs...
June 26, 2017: Oncogene
https://www.readbyqxmd.com/read/28649883/middle-down-proteomics-a-still-unexploited-resource-for-chromatin-biology
#2
Simone Sidoli, Benjamin A Garcia
Introduction Analysis of histone post-translational modifications (PTMs) by mass spectrometry (MS) has become a fundamental tool for the characterization of chromatin composition and dynamics. Histone PTMs benchmark several biological states of chromatin, including regions of active enhancers, active/repressed gene promoters and damaged DNA. These complex regulatory mechanisms are often defined by combinatorial histone PTMs; for instance, active enhancers are commonly occupied by both marks H3K4me1 and H3K27ac...
June 26, 2017: Expert Review of Proteomics
https://www.readbyqxmd.com/read/28645654/epigenome-dysregulation-in-cholangiocarcinoma
#3
REVIEW
Colm J O'Rourke, Patricia Munoz-Garrido, Esmeralda L Aguayo, Jesper B Andersen
Epigenomics is a fast-evolving field of research that has lately attracted considerable interest, mainly due to the reversibility of epigenetic marks. Clinically, among solid tumors, the field is still limited. In cholangiocarcinoma (CCA) it is well known that the epigenetic landscape is deregulated both during carcinogenesis and disease progression as a consequence of aberrant mechanisms leading to genome instability. In this article, we will briefly review the molecular alterations that have been described in the transformation of normal cholangiocytes into malignant derivatives, focusing on the role of non-coding RNA (ncRNA) interactions, DNA methylation, post-translational modifications (PTMs) of histones and chromatin remodeling complexes...
June 20, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28645514/bcl-xl-deamidation-and-cancer-charting-the-fame-trajectories-of-legitimate-child-and-hidden-siblings
#4
REVIEW
Florian Beaumatin, Mohamad El Dhaybi, Claude Bobo, Mireille Verdier, Muriel Priault
Bcl-2 family proteins control programmed cell death through a complex network of interactions within and outside of this family, that are modulated by post-translational modifications (PTM). Bcl-xL, an anti-apoptotic member of this family, is overexpressed in a number of cancers, plays an important role in tumorigenesis and is correlated with drug resistance. Bcl-xL is susceptible to a number of different PTMs. Here, we focus on deamidation. We will first provide an overview of protein deamidation. We will then review how the apoptotic and autophagic functions of Bcl-xL are modified by this PTM, and how this impacts on its oncogenic properties...
June 20, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28644004/the-intricate-effects-of-alpha-amino-and-lysine-modifications-on-arginine-methylation-on-the-n-terminal-tail-of-histone-h4
#5
Melody D Fulton, Jing Zhang, Maomao He, Meng-Chiao Ho, Y George Zheng
Chemical modifications on the DNA and nucleosomal histones tightly control the gene transcription program in eukaryotic cells. The "histone code" hypothesis proposes that the frequency, combination, and location of post-translational modifications (PTMs) on the core histones compose a complex network of epigenetic regulation. Currently, there are at least 23 different types and over 450 histone PTMs discovered, and the PTMs on lysine and arginine residues account for a crucial part of the histone code. Although significant progress has been achieved in recent years, the molecular basis for the histone code is far from being fully understood...
June 23, 2017: Biochemistry
https://www.readbyqxmd.com/read/28636386/msviz-a-graphical-software-tool-for-in-depth-manual-validation-and-quantitation-of-post-translational-modifications
#6
Trinidad Martin Campos, Roman Mylonas, Alexandre Masselot, Patrice Waridel, Tanja Petricevic, Ioannis Xenarios, Manfredo Quadroni
Mass spectrometry (MS) has become the tool of choice for the large scale identification and quantitation of proteins and their post-translational modifications (PTMs). This development has been enabled by powerful software packages for the automated analysis of MS data. While data on PTM's of thousands of proteins can nowadays be readily obtained, fully deciphering the complexity and combinatorics of modification patterns even on a single protein often remains challenging. Moreover, functional investigation of PTMs on a protein of interest requires validation of the localization and the accurate quantitation of its changes across several conditions, tasks that often still require human evaluation...
June 21, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28629911/combined-mass-spectrometry-imaging-and-top-down-microproteomics-reveals-evidence-of-a-hidden-proteome-in-ovarian-cancer
#7
Vivian Delcourt, Julien Franck, Eric Leblanc, Fabrice Narducci, Yves-Marie Robin, Jean-Pascal Gimeno, Jusal Quanico, Maxence Wisztorski, Firas Kobeissy, Jean-François Jacques, Xavier Roucou, Michel Salzet, Isabelle Fournier
BACKGROUND: Recently, it was demonstrated that proteins can be translated from alternative open reading frames (altORFs), increasing the size of the actual proteome. Top-down mass spectrometry-based proteomics allows the identification of intact proteins containing post-translational modifications (PTMs) as well as truncated forms translated from reference ORFs or altORFs. METHODS: Top-down tissue microproteomics was applied on benign, tumor and necrotic-fibrotic regions of serous ovarian cancer biopsies, identifying proteins exhibiting region-specific cellular localization and PTMs...
June 3, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28629773/bering-the-burden-of-damage-pathway-crosstalk-and-posttranslational-modification-of-base-excision-repair-proteins-regulate-dna-damage-management
#8
REVIEW
Kristin L Limpose, Anita H Corbett, Paul W Doetsch
DNA base damage and non-coding apurinic/apyrimidinic (AP) sites are ubiquitous types of damage that must be efficiently repaired to prevent mutations. These damages can occur in both the nuclear and mitochondrial genomes. Base excision repair (BER) is the frontline pathway for identifying and excising damaged DNA bases in both of these cellular compartments. Recent advances demonstrate that BER does not operate as an isolated pathway but rather dynamically interacts with components of other DNA repair pathways to modulate and coordinate BER functions...
June 9, 2017: DNA Repair
https://www.readbyqxmd.com/read/28628292/an-environment-sensitive-turn-on-fluorescent-polyamino-acid-fingerprinting-protein-populations-with-post-translational-modifications
#9
Shunsuke Tomita, Sayaka Ishihara, Ryoji Kurita
The identification of post-translational modifications (PTMs) in proteins has been of particular interest in the elucidation of human diseases and the improvement of therapeutic proteins. Herein, we report a novel strategy toward the construction of fingerprint-based PTM sensing systems as an alternative to conventional specific recognition tools. Our strategy is based on poly-L-lysine (PLL) derivatives with two distinct properties suitable to fingerprint-based protein sensing: i) a "turn-on" fluorescent signal upon binding to proteins, and ii) condition-dependent cross-reactivity toward proteins and PTMs...
June 19, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28627251/direct-lc-ms-analysis-for-complete-characterization-of-recombinant-adeno-associated-virus-capsid-proteins
#10
Xiaoying Jin, Lin Liu, Shelley Nass, Catherine R O'Riordan, Eric Pastor, Kate Xiaokui Zhang
The requirement for robust analytical methods to support characterization of Adeno-Associated Virus (AAV) vectors is immediate, as the field advances more AAV gene therapeutics into the clinic and onto commercialization. AAV capsid proteins (VPs) are critical for viral infectivity and vector potency, thus, complete characterization of the constituent viral capsid proteins of AAV vector therapeutics, including their sequence and post-translational modifications (PTMs), is highly recommended to ensure AAV product quality and consistency...
June 18, 2017: Human Gene Therapy Methods
https://www.readbyqxmd.com/read/28617227/in-silico-re-identification-of-properties-of-drug-target-proteins
#11
Baeksoo Kim, Jihoon Jo, Jonghyun Han, Chungoo Park, Hyunju Lee
BACKGROUND: Computational approaches in the identification of drug targets are expected to reduce time and effort in drug development. Advances in genomics and proteomics provide the opportunity to uncover properties of druggable genomes. Although several studies have been conducted for distinguishing drug targets from non-drug targets, they mainly focus on the sequences and functional roles of proteins. Many other properties of proteins have not been fully investigated. METHODS: Using the DrugBank (version 3...
May 31, 2017: BMC Bioinformatics
https://www.readbyqxmd.com/read/28615324/hihimap-single-cell-quantitation-of-histones-and-histone-post-translational-modifications-across-the-cell-cycle-by-high-throughput-imaging
#12
Linda Zane, Fleur Chapus, Gianluca Pegoraro, Tom Misteli
We describe HiHiMap (High-throughput Histone Mapping), a high-throughput imaging method to measure histone and histone post-translational modifications (PTM) in single cells. HiHiMap uses imaging-based quantification of DNA and Cyclin A to stage individual cells in the cell cycle to determine the levels of histone or histone PTMs in each stage of the cell cycle. As proof-of-principle, we apply HiHiMap to measure the level of 21 core histones, histone variants and PTMs in primary, immortalized and transformed cells...
June 14, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28609623/single-step-enrichment-of-n-glycopeptides-and-phosphopeptides-with-novel-multifunctional-ti4-immobilized-dendritic-polyglycerol-coated-chitosan-nanomaterials
#13
Xiajuan Zou, Jianzheng Jie, Bin Yang
Protein glycosylation and phosphorylation, two of the most important post-translational modifications (PTMs) in the proteome play a vital role in regulating a number of complex biological processes and involvement in a variety of diseases. Comprehensive characterization of the phosphoproteome and glycoproteome requires highly specific and sensitive enrichment methods for purification of phosphopeptides and glycopeptides because many glycoproteins and phosphoproteins naturally occur at low abundances and substoichiometry...
June 13, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28606917/quantitative-temporal-viromics-of-an-inducible-hiv-1-model-yields-insight-to-global-host-targets-and-phospho-dynamics-associated-with-vpr
#14
John D Lapek, Mary K Lewinski, Jacob M Wozniak, John Guatelli, David J Gonzalez
The mechanisms by which human immunodeficiency virus (HIV) circumvents and coopts cellular machinery to replicate and persist in cells are not fully understood. HIV accessory proteins play key roles in the HIV life cycle by altering host pathways that are often dependent on post-translational modifications (PTMs). Thus, the identification of HIV accessory protein host targets and their PTM status is critical to fully understand how HIV invades, avoids detection and replicates to spread infection. To date, a comprehensive characterization of HIV accessory protein host targets and modulation of their PTM status does not exist...
June 12, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28604659/inference-and-quantification-of-peptidoforms-in-large-sample-cohorts-by-swath-ms
#15
George Rosenberger, Yansheng Liu, Hannes L Röst, Christina Ludwig, Alfonso Buil, Ariel Bensimon, Martin Soste, Tim D Spector, Emmanouil T Dermitzakis, Ben C Collins, Lars Malmström, Ruedi Aebersold
Consistent detection and quantification of protein post-translational modifications (PTMs) across sample cohorts is a prerequisite for functional analysis of biological processes. Data-independent acquisition (DIA) is a bottom-up mass spectrometry approach that provides complete information on precursor and fragment ions. However, owing to the convoluted structure of DIA data sets, confident, systematic identification and quantification of peptidoforms has remained challenging. Here, we present inference of peptidoforms (IPF), a fully automated algorithm that uses spectral libraries to query, validate and quantify peptidoforms in DIA data sets...
June 12, 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/28589199/the-strategies-for-identification-and-quantification-of-sumoylation
#16
Yan Zhang, Yueying Li, Bo Tang, Chun-Yang Zhang
SUMOylation is a post-translational modification that plays critical roles in a multitude of cellular processes including transcription, cellular localization, DNA repair and cell cycle progression. Similar to ubiquitin, the small ubiquitin-like modifiers (SUMOs) are covalently attached to the epsilon amino group of lysine residues in the substrates. To understand the regulation and the dynamics of post-translational modifications (PTMs), the identification and quantification of SUMOylation is strictly needed...
June 7, 2017: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/28582861/post-translational-oxidative-modifications-of-mitochondrial-complex-i-nadh-ubiquinone-oxidoreductase-implications-for-pathogenesis-and-therapeutics-in-human-diseases
#17
M M Srinivas Bharath
Mitochondrial complex I (NADH: ubiquinone oxidoreductase; CI) is central to the electron transfer chain (ETC), oxidative phosphorylation, and ATP production in eukaryotes. CI is a multi-subunit complex with a complicated yet organized structure that optimally connects electron transfer with proton translocation and forms higher-order supercomplexes with other ETC complexes. Efforts to understand the molecular genetics, expression profile of subunits, and structure-function relationship of CI have increased over the years due to the direct role of the complex in human diseases...
May 30, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28570536/isolation-of-intermediate-filament-proteins-from-multiple-mouse-tissues-to-study-aging-associated-post-translational-modifications
#18
Rachel A Battaglia, Parijat Kabiraj, Helen H Willcockson, Melinda Lian, Natasha T Snider
Intermediate filaments (IFs), together with actin filaments and microtubules, form the cytoskeleton - a critical structural element of every cell. Normal functioning IFs provide cells with mechanical and stress resilience, while a dysfunctional IF cytoskeleton compromises cellular health and has been associated with many human diseases. Post-translational modifications (PTMs) critically regulate IF dynamics in response to physiological changes and under stress conditions. Therefore, the ability to monitor changes in the PTM signature of IFs can contribute to a better functional understanding, and ultimately conditioning, of the IF system as a stress responder during cellular injury...
May 18, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28558143/parsing-disease-relevant-protein-modifications-from-epiphenomena-perspective-on-the-structural-basis-of-sod1-mediated-als
#19
N D Schmitt, J N Agar
Conformational change and modification of proteins are involved in many cellular functions. However, they can also have adverse effects that are implicated in numerous diseases. How structural change promotes disease is generally not well understood. This perspective illustrates how mass spectrometry (MS), followed by toxicological and epidemiological validation, can discover disease-relevant structural changes and therapeutic strategies. We (with our collaborators) set out to characterize the structural and toxic consequences of disease-associated mutations and post-translational modifications (PTMs) of the cytosolic antioxidant protein Cu/Zn-Superoxide dismutase (SOD1)...
May 30, 2017: Journal of Mass Spectrometry: JMS
https://www.readbyqxmd.com/read/28553538/site-selective-reading-of-epigenetic-markers-by-a-dual-mode-synthetic-receptor-array
#20
Yang Liu, Lizeth Perez, Magi Mettry, Adam D Gill, Samantha R Byers, Connor J Easley, Christopher J Bardeen, Wenwan Zhong, Richard J Hooley
Variably functionalized self-folding deep cavitands form an arrayed, fluorescent indicator displacement assay system for the detection of post-translationally modified (PTM) histone peptides. The hosts bind trimethyllysine (KMe3) groups, and use secondary upper rim interactions to provide more sensitive discrimination between targets with identical KMe3 binding handles. The sensor array uses multiple different recognition modes to distinguish between miniscule differences in target, such as identical lysine modifications at different sites of histone peptides...
May 1, 2017: Chemical Science
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