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Molecular & Cellular Proteomics: MCP

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https://www.readbyqxmd.com/read/28336726/proteomic-signature-of-acute-liver-failure-from-discovery-and-verification-in-a-pig-model-to-confirmation-in-humans
#1
Jie Wang, Zeyu Sun, Jing Jiang, Daxian Wu, Xiaoli Liu, Zhongyang Xie, Ermei Chen, Danhua Zhu, Chao Ye, Xiaoqian Zhang, Wenqian Chen, Hongcui Cao, Lanjuan Li
Acute liver failure (ALF) is a fatal condition hallmarked by rapid development. The present study aimed to describe the dynamic alterations of serum proteins associated with ALF development, and to seek for novel biomarkers of ALF. Miniature pigs (n=30) were employed to establish ALF models by infusing D-galactosamine (GALN, 1.3g/kg). A total of 1589 serum proteins were compared in pooled serum samples (n=10) before and 36 hours after GALN administration through label-free quantitation (LFQ) based shotgun proteomics...
March 23, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28336725/quantitative-shotgun-proteomics-unveils-candidate-novel-oesophageal-adenocarcinoma-specific-proteins
#2
J Robert O'Neill, Hui-Song Pak, Erola Pairo-Castineira, Vicki Save, Simon Paterson-Brown, Rudolf Nenutil, Bořivoj Vojtěšek, Ian Overton, Alex Scherl, Ted R Hupp
Oesophageal cancer is the eighth most common cancer worldwide and the majority of patients have systemic disease at presentation. Oesophageal adenocarcinoma (OAC), the predominant subtype in western countries, is largely resistant to current chemotherapy regimens. Selective markers are needed to enhance clinical staging and to allow targeted therapies yet there are minimal proteomic data on this cancer type. After histological review, lysates from OAC and matched normal oesophageal and gastric samples from seven patients were subjected to LC MS/MS after tandem mass tag labelling and OFFGEL fractionation...
March 23, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28336724/quantitative-age-specific-variability-of-plasma-proteins-in-healthy-neonates-children-and-adults
#3
Stefan Bjelosevic, Dana Pascovici, Hui Ping, Vasiliki Karlaftis, Thiri Zaw, Xiaomin Song, Mark P Molloy, Paul Monagle, Vera Ignjatovic
Human blood plasma is a complex biological fluid containing soluble proteins, sugars, hormones, electrolytes, and dissolved gasses. As plasma interacts with a wide array of bodily systems, changes in protein expression, or the presence or absence of specific proteins are regularly used in the clinic as a molecular biomarker tool. A large body of literature exists detailing proteomic changes in pathologic contexts, however little research has been conducted on the quantitation of the plasma proteome in age-specific, healthy subjects, especially in pediatrics...
March 23, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28336715/monitoring-cell-surface-n-glycoproteome-dynamics-by-quantitative-proteomics-reveals-mechanistic-insights-into-macrophage-differentiation
#4
Mathias Kalxdorf, Stephan Gade, H Christian Eberl, Marcus Bantscheff
The plasma membrane proteome plays a crucial role in inter- and intracellular signaling, cell survival and cell identity. As such it is a prominent target for pharmacological intervention. The relatively low abundance of this subproteome in conjunction with challenging extractability and solubility still hampers their comprehensive analysis. Here, we combined a chemical glycoprotein tagging strategy with mass spectrometry to enable comprehensive analysis of the cell surface glycoprotome. To benchmark this workflow and provide guidance for cell line selection for functional experiments, we generated an inventory of the N-linked cell surface glycoproteome of 15 standard laboratory human cell lines and three primary lymphocytic cell types...
March 23, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28331001/quantitative-tyrosine-phosphoproteomics-of-egfr-tyrosine-kinase-inhibitor-treated-lung-adenocarcinoma-cells-reveals-potential-novel-biomarkers-of-therapeutic-response
#5
Xu Zhang, Tapan Maity, Manoj K Kashyap, Mukesh Bansal, Abhilash Venugopalan, Sahib Singh, Shivangi Awasthi, Arivusudar Marimuthu, Harrys Kishore Charles Jacob, Natalya Belkina, Stephanie Pitts, Constance M Cultraro, Shaojian Gao, Fatos Kirkali, Romi Biswas, Raghothama Chaerkady, Andrea Califano, Akhilesh Pandey, Udayan Guha
Mutations in the Epidermal growth factor receptor (EGFR) kinase domain, such as the L858R missense mutation and deletions spanning the conserved sequence 747LREA750, are sensitive to tyrosine kinase inhibitors (TKIs). The gatekeeper site residue mutation, T790M accounts for around 60% of acquired resistance to EGFR TKIs. The first generation EGFR TKIs, erlotinib and gefitinib, and the second generation inhibitor, afatinib are FDA approved for initial treatment of EGFR mutated lung adenocarcinoma. The predominant biomarker of EGFR TKI responsiveness is the presence of EGFR TKI-sensitizing mutations...
March 22, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28325852/extended-multiplexing-of-tmt-labeling-reveals-age-and-high-fat-diet-specific-proteome-changes-in-mouse-epididymal-adipose-tissue
#6
Deanna L Plubell, Phillip A Wilmarth, Yuqi Zhao, Alexandra M Fenton, Jessica Minnier, Ashok P Reddy, John Klimek, Xia Yang, Larry L David, Nathalie Pamir
The lack of high-throughput methods to analyze the adipose tissue protein composition limits our understanding of the protein networks responsible for age and diet related metabolic response. We have developed an approach using multiple-dimension liquid chromatography tandem mass spectrometry and extended multiplexing (24 biological samples) with TMT labeling to analyze proteomes of epididymal adipose tissues isolated from mice fed either low or high fat diet for a short or a long-term, and from mice that aged on low vs...
March 21, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28325851/new-quantitative-mass-spectrometry-approaches-reveal-different-adp-ribosylation-phases-dependent-on-the-levels-of-oxidative-stress
#7
Vera Bilan, Nathalie Selevsek, Hans A V Kistemaker, Jeannette Abplanalp, Roxane Feurer, Dmitri V Filippov, Michael O Hottiger
Oxidative stress is a potent inducer of protein ADP-ribosylation. Although individual oxidative stress-induced ADP-ribosylated proteins have been identified, it is so far not clear, to which extent different degrees of stress severity quantitatively and qualitatively alter ADP-ribosylation, respectively. Here, we investigated both quantitative and qualitative changes of the hydrogen peroxide (H2O2)-induced ADP-ribosylome using a label-free shotgun quantification and a parallel reaction monitoring (PRM) mass spectrometry approach for a selected number of identified ADP-ribosylated peptides...
March 21, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28302922/covariation-of-peptide-abundances-accurately-reflects-protein-concentration-differences
#8
Bo Zhang, Mohammad Pirmoradian, Roman Zubarev, Lukas Käll
Most implementations of mass spectrometry-based proteomics involve enzymatic digestion of proteins, expanding the analysis to multiple proteolytic peptides for each protein. Currently, there is no consensus of how to summarize peptides' abundances to protein concentrations, and such efforts are complicated by the fact that error control is normally applied to the identification process, and do not directly control errors linking peptide abundance measures to protein concentration. Peptides resulting from suboptimal digestion or being partially modified are not representative of the protein concentration...
March 16, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28302921/deciphering-the-acute-cellular-phosphoproteome-response-to-irradiation-with-x-rays-protons-and-carbon-ions
#9
Martin Winter, Ivana Dokic, Julian Schlegel, Uwe Warnken, Jürgen Debus, Amir Abdollahi, Martina Schnölzer
Radiotherapy is a cornerstone of cancer therapy. The recently established particle therapy with raster-scanning protons and carbon ions landmarks a new era in the field of high-precision cancer medicine. However, molecular mechanisms governing radiation induced intracellular signaling remain elusive. Here, we present the first comprehensive proteomic and phosphoproteomic study applying stable isotope labeling by amino acids in cell culture (SILAC) in combination with high-resolution mass spectrometry to decipher cellular response to irradiation with X-rays, protons and carbon ions...
March 16, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28298517/phosphoproteomics-of-fgf1-signaling-in-chondrocytes-identifying-the-signature-of-inhibitory-response
#10
Jessica R Chapman, Olga Katsara, Rachel Ruoff, David Morgenstern, Shruti Nayak, Claudio Basilico, Beatrix Ueberheide, Victoria Kolupaeva
Fibroblast growth factor (FGF) signaling is vital for many biological processes, beginning with development. The importance of FGF signaling for skeleton formation was first discovered by the analysis of genetic FGFR mutations which cause several bone morphogenetic disorders, including achondroplasia, the most common form of human dwarfism. The formation of the long bones is mediated through proliferation and differentiation of highly specialized cells - chondrocytes. Chondrocytes respond to FGF with growth inhibition, a unique response which differs from the proliferative response of the majority of cell types; however its molecular determinants are still unclear...
March 15, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28292943/molecular-details-underlying-dynamic-structures-and-regulation-of-the-human-26s-proteasome
#11
Xiaorong Wang, Peter Cimermancic, Clinton Yu, Andreas Schweitzer, Nikita Chopra, James L Engel, Charles H Greenberg, Alexander S Huszagh, Florian Beck, Eri Sakata, Yingying Yang, Eric J Novitsky, Alexander Leitner, Paolo Nanni, Abdullah Kahraman, Xing Guo, Jack E Dixon, Scott D Rychnovsky, Ruedi Aebersold, Wolfgang Baumeister, Andrej Sali, Lan Huang
The 26S proteasome is the macromolecular machine responsible for ATP/ubiquitin dependent degradation. As aberration in proteasomal degradation has been implicated in many human diseases, structural analysis of the human 26S proteasome complex is essential to advance our understanding of its action and regulation mechanisms. In recent years, cross-linking mass spectrometry (XL-MS) has emerged as a powerful tool for elucidating structural topologies of large protein assemblies, with its unique capability of studying protein complexes in cells...
March 14, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28289178/proteome-wide-mapping-of-endogenous-sumoylation-sites-in-mouse-testis
#12
Lili Cai, Jun Tu, Lei Song, Zhihua Gao, Kai Li, Yunzhi Wang, Yang Liu, Fan Zhong, Rui Ge, Jun Qin, Chen Ding, Fuchu He
SUMOylation is a reversible post-translational modification involved in various critical biological processes. To date, there is limited approach for endogenous wild-type SUMO-modified peptides enrichment and SUMOylation sites identification. In this study, we generated a high-affinity SUMO1 antibody to facilitate the enrichment of endogenous SUMO1-modified peptides from Trypsin/Lys-C protease digestion. Following secondary Glu-C protease digestion, we identified 53 high-confidence SUMO1-modified sites from mouse testis by using high-resolution mass spectrometry...
March 13, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28289177/structural-diversity-of-human-gastric-mucin-glycans
#13
Chunsheng Jin, Diarmuid T Kenny, Emma C Skoog, Medéa Padra, Barbara Adamczyk, Varvara Vitizeva, Anders Thorell, Vignesh Venkatakrishnan, Sara K Lindén, Niclas G Karlsson
The mucin O-glycosylation of 10 individuals with and without gastric disease was examined in depth in order to generate a structural map of human gastric glycosylation. In the stomach, these mucins and their O-glycosylation protect the epithelial surface from the acidic gastric juice and provide the first point of interaction for pathogens such as Helicobacter pylori, reported to cause gastritis, gastric and duodenal ulcers and gastric cancer. The rational of the present study was to map the O-glycosylation that the pathogen may come in contact with...
March 13, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28289176/quantitative-proteomic-approach-identifies-vpr-binding-protein-as-novel-host-factor-supporting-influenza-a-virus-infections-in-human-cells
#14
Anne Sadewasser, Katharina Paki, Katrin Eichelbaum, Boris Bogdanow, Sandra Saenger, Matthias Budt, Markus Lesch, Klaus-Peter Hinz, Andreas Herrmann, Thomas F Meyer, Alexander Karlas, Matthias Selbach, Thorsten Wolff
Influenza A virus infections are a major cause for respiratory disease in humans, which affects all age groups and contributes substantially to global morbidity and mortality. IAV have a large natural host reservoir in avian species. However, many avian IAV strains lack adaptation to other hosts and hardly propagate in humans. While seasonal or pandemic influenza A virus (IAV) strains replicate efficiently in permissive human cells, many avian IAV cause abortive non-productive infections in these hosts despite successful cell entry...
March 13, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28283547/the-host-pathogen-ecosystem-viewed-through-the-prism-of-proteomics
#15
Ileana M Cristea
N/A.
March 10, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28275051/protein-footprinting-comes-of-age-mass-spectrometry-for-biophysical-structure-assessment
#16
Liwen Wang, Mark R Chance
Protein footprinting mediated by mass spectrometry has evolved over the last 30 years from proof of concept to commonplace biophysics tool, with unique capabilities for assessing structure and dynamics of purified proteins in physiological states in solution. This review outlines the history and current capabilities of two major methods of protein footprinting: reversible hydrogen-deuterium exchange (HDX) and hydroxyl radical footprinting (HRF), an irreversible covalent labeling approach. Technological advances in both approaches now permit high-resolution assessments of protein structure including secondary and tertiary structure stability mediated by backbone interactions (measured via HDX) and solvent accessibility of side chains (measured via HRF)...
March 8, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28265048/machine-learning-of-global-phosphoproteomic-profiles-enables-discrimination-of-direct-versus-indirect-kinase-substrates
#17
Evgeny Kanshin, Sebastien Giguere, Jing Cheng, Michael D Tyers, Pierre Thibault
Mass spectrometry allows quantification of tens of thousands of phosphorylation sites from minute amounts of cellular material. Despite this wealth of information, our understanding of phosphorylation-based signaling is limited, in part because it is not possible to deconvolute substrate phosphorylation that is directly mediated by a particular kinase versus phosphorylation that is mediated by downstream kinases. Here, we describe a framework for assignment of direct in-vivo kinase substrates using a combination of selective chemical inhibition, quantitative phosphoproteomics, and machine learning techniques...
March 6, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28265047/human-immunoglobulin-heavy-gamma-chain-polymorphisms-molecular-confirmation-of-proteomic-assessment
#18
Magalie Dambrun, Célia Dechavanne, Alexandra Emmanuel, Florentin Aussenac, Marjorie Leduc, Chiara Giangrande, Joëlle Vinh, Jean-Michel Dugoujon, Marie-Paule Lefranc, François Guillonneau, Florence Migot-Nabias
Immunoglobulin G (IgG) proteins are known for the huge diversity of the variable domains of their heavy and light chains, aimed at protecting each individual against foreign antigens. The IgG also harbor specific polymorphism concentrated in the CH2 and CH3-CHS constant regions located on the Fc fragment of their heavy chains. But this individual particularity relies only on a few amino acids among which some could make accurate sequence determination a challenge for mass spectrometry-based techniques. The purpose of the study was to bring a molecular validation of proteomic results by the sequencing of encoding DNA fragments...
March 6, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28254776/accurate-quantification-of-site-specific-acetylation-stoichiometry-reveals-the-impact-of-sirtuin-deacetylase-cobb-on-the-e-coli-acetylome
#19
Brian Tate Weinert, Shankha Satpathy, Bogi Karbech Hansen, David Lyon, Lars Juhl Jensen, Chunaram Choudhary
Lysine acetylation is a protein posttranslational modification (PTM) that occurs on thousands of lysine residues in diverse organisms from bacteria to humans. Accurate measurement of acetylation stoichiometry on a proteome-wide scale remains challenging. Most methods employ a comparison of chemically acetylated peptides to native acetylated peptides, however, the potentially large differences in abundance between these peptides presents a challenge for accurate quantification. Stable isotope labeling by amino acids in cell culture (SILAC)-based mass spectrometry (MS) is one of the most widely used quantitative proteomic methods...
March 2, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28254775/global-analysis-of-sumo-binding-proteins-identifies-sumoylation-as-a-key-regulator-of-the-ino80-chromatin-remodeling-complex
#20
Eric Cox, Woochang Hwang, Ijeoma Uzoma, Jianfei Hu, Catherine Guzzo, Junseop Jeong, Michael Matunis, Jiang Qian, Heng Zhu, Seth Blackshaw
SUMOylation is a critical regulator of a broad range of cellular processes, and is thought to do so in part by modulation of protein interaction. To comprehensively identify human proteins whose interaction is modulated by SUMOylation, we developed an in vitro binding assay using human proteome microarrays to identify targets of SUMO1 and SUMO2. We then integrated these results with protein SUMOylation and protein-protein interaction data to perform network motif analysis. We focused on a single network motif we termed a SUMOmodPPI (SUMO-modulated Protein-Protein Interaction) that included the INO80 chromatin remodeling complex subunits TFPT and INO80E...
March 2, 2017: Molecular & Cellular Proteomics: MCP
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