Abstract：
:Protein phosphorylation is a reversible post-translational modification that regulates many biological processes in almost all living forms. In the case of the hepatitis C virus (HCV), the nonstructural protein 5A (NS5A) is believed to transit between hypo- and hyper-phosphorylated forms that interact with host proteins to execute different functions; however, little was known about the proteins that bind either form of NS5A. Here, we generated two high-quality antibodies specific to serine 235 nonphosphorylated hypo- vs serine 235 phosphorylated (pS235) hyper-phosphorylated form of NS5A and for the first time segregated these two forms of NS5A plus their interacting proteins for dimethyl-labeling based proteomics. We identified 629 proteins, of which 238 were quantified in three replicates. Bioinformatics showed 46 proteins that preferentially bind hypo-phosphorylated NS5A are involved in antiviral response and another 46 proteins that bind pS235 hyper-phosphorylated NS5A are involved in liver cancer progression. We further identified a DNA-dependent kinase (DNA-PK) that binds hypo-phosphorylated NS5A. Inhibition of DNA-PK with an inhibitor or via gene-specific knockdown significantly reduced S232 phosphorylation and NS5A hyper-phosphorylation. Because S232 phosphorylation initiates sequential S232/S235/S238 phosphorylation leading to NS5A hyper-phosphorylation, we identified a new protein kinase that regulates a delicate balance of NS5A between hypo- and hyper-phosphorylation states, respectively, involved in host antiviral responses and liver cancer progression.
journal_name
J Proteome Resjournal_title
Journal of proteome researchauthors
Pan TC,Lo CW,Chong WM,Tsai CN,Lee KY,Chen PY,Liao JC,Yu MJdoi
10.1021/acs.jproteome.9b00130subject
Has Abstractpub_date
2019-07-05 00:00:00pages
2813-2825issue
7eissn
1535-3893issn
1535-3907journal_volume
18pub_type
杂志文章abstract：:We report the proteomic characterization and biological activities of the venom of the black-speckled palm pitviper, Bothriechis nigroviridis, a neotropical arboreal pitviper from Costa Rica. In marked contrast to other Bothriechis species investigated, the venom of B. nigroviridis does not possess detectable Zn(2+)-d...
journal_title：Journal of proteome research
pub_type： 杂志文章
doi：10.1021/pr100545d
更新日期：2010-08-06 00:00:00
abstract：:The present study was undertaken to identify proteins interacting with PrP(C) that could provide new insights into its physiological functions and pathological role. Human PrP(C) was expressed in prion protein-deficient murine hippocampus (HpL3-4) neuronal cells. The PrP(C) along with its interacting proteins were aff...
journal_title：Journal of proteome research
pub_type： 杂志文章
doi：10.1021/pr2001989
更新日期：2011-07-01 00:00:00
abstract：:A major challenge in the life sciences is the extraction of detailed molecular information from plants and animals that are not among the handful of exhaustively studied "model organisms." As a consequence, certain species with novel phenotypes are often ignored due to the lack of searchable databases, tractable genet...
journal_title：Journal of proteome research
pub_type： 杂志文章
doi：10.1021/pr050306a
更新日期：2006-04-01 00:00:00
abstract：:Serum protein profiling by mass spectrometry is a promising method for early detection of cancer. We have implemented a combined strategy based on matrix-assisted laser desorption ionization mass spectrometry (MALDI MS) and statistical data analysis for serum protein profiling and applied it in a well-described breast...
journal_title：Journal of proteome research
pub_type： 杂志文章
doi：10.1021/pr7007576
更新日期：2008-04-01 00:00:00
abstract：:Redox regulation plays an important role across a broad spectrum of biology. Accumulating evidence suggests that thioredoxin, a widely distributed redox enzyme, participates in the redox control of numerous target proteins, thus, playing a key role as a signaling intermediate that senses the metabolic state or environ...
journal_title：Journal of proteome research
pub_type： 杂志文章,评审
doi：10.1021/pr8003453
更新日期：2008-08-01 00:00:00
abstract：:The bacterial ribosomal protein S12 contains a universally conserved D88 residue on a loop region thought to be critically involved in translation due to its proximal location to the A site of the 30S subunit. While D88 mutants are lethal this residue has been found to be post-translationally modified to β-methylthioa...
journal_title：Journal of proteome research
pub_type： 杂志文章
doi：10.1021/pr3009435
更新日期：2013-03-01 00:00:00
abstract：:Histone post-translational modifications (PTMs) are fundamental players of chromatin regulation, as they contribute to editing histone chemical properties and recruiting proteins for gene transcription and DNA repair. Mass spectrometry (MS)-based proteomics is currently the most widely adopted strategy for high-throug...
journal_title：Journal of proteome research
pub_type： 杂志文章
doi：10.1021/acs.jproteome.7b00544
更新日期：2018-01-05 00:00:00
abstract：:The SEQUEST program was the first and remains one of the most widely used tools for assigning a peptide sequence within a database to a tandem mass spectrum. The cross correlation score is the primary score function implemented within SEQUEST and it is this score that makes the tool particularly sensitive. Unfortunate...
journal_title：Journal of proteome research
pub_type： 杂志文章
doi：10.1021/pr800420s
更新日期：2008-10-01 00:00:00
abstract：:A "one-pot" alternative method for processing proteins and isolating peptide mixtures from bacterial samples is presented for liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis and data reduction. The conventional in-solution digestion of the protein contents of bacteria is compared to a small disposab...
journal_title：Journal of proteome research
pub_type： 杂志文章
doi：10.1021/pr101086a
更新日期：2011-02-04 00:00:00
abstract：:Sperm proteomes have emerged for several species; however, the extent of species similarity is unknown. Sheep are an important agricultural species for which a comprehensive sperm proteome has not been produced. In addition, potential proteomic factors from seminal plasma that may contribute to improved fertility afte...
journal_title：Journal of proteome research
pub_type： 杂志文章
doi：10.1021/acs.jproteome.6b00530
更新日期：2016-10-07 00:00:00
abstract：:A detailed understanding of the relationships between the distinct metabolic compartments of blood and milk would be of potential benefit to our understanding of the physiology of lactation, and potentially for development of biomarkers for health and commercially relevant traits in dairy cattle. NMR methods were used...
journal_title：Journal of proteome research
pub_type： 杂志文章
doi：10.1021/pr301056q
更新日期：2013-03-01 00:00:00
abstract：:During asexual intraerythrocytic development, Plasmodium falciparum diverges from the paradigm of the eukaryotic cell cycles by undergoing multiple rounds of DNA replication and nuclear division without cytokinesis. A better understanding of the molecular switches that coordinate a myriad of events for the progression...
journal_title：Journal of proteome research
pub_type： 杂志文章
doi：10.1021/pr400394g
更新日期：2013-09-06 00:00:00
abstract：:The proteome of any system is a dynamic entity, such that the intracellular concentration of a protein is dictated by the relative rates of synthesis and degradation. In this work, we have analyzed time-dependent changes in the incorporation of a stable amino acid resolved precursor, a protocol we refer to as "dynamic...
journal_title：Journal of proteome research
pub_type： 杂志文章
doi：10.1021/pr800641v
更新日期：2009-01-01 00:00:00
abstract：:Roux-en-Y gastric bypass (RYGB) is one of the most effective treatments for long-term weight loss and diabetes remission; however, the mechanisms underlying these changes are not clearly understood. In this study, the serum metabolic profiles of 23 remission and 12 nonremission patients with type 2 diabetes mellitus (...
journal_title：Journal of proteome research
pub_type： 杂志文章
doi：10.1021/acs.jproteome.6b00022
更新日期：2016-04-01 00:00:00
abstract：:The skin is the primary boundary between the body and the environment. In addition to its properties as a physical barrier, skin keratinocytes actively participate in many defense mechanisms. Viral double-stranded RNA (dsRNA) is the most important viral structure involved in activation of immune response. Intracellula...
journal_title：Journal of proteome research
pub_type： 杂志文章
doi：10.1021/pr901040u
更新日期：2010-03-05 00:00:00
abstract：:To assess the global effect of preterm birth on fetal metabolism and maternal-fetal nutrient transfer, we used a mass spectrometric-based chemical phenotyping approach on cord blood obtained at the time of birth. We sampled umbilical venous, umbilical arterial, and maternal blood from mothers delivering very-low birth...
journal_title：Journal of proteome research
pub_type： 杂志文章
doi：10.1021/pr400122v
更新日期：2013-06-07 00:00:00
abstract：:Knowledge of protein subcellular localization assists in the elucidation of protein function and understanding of different biological mechanisms that occur at discrete subcellular niches. Organelle-centric proteomics enables localization of thousands of proteins simultaneously. Although such techniques have successfu...
journal_title：Journal of proteome research
pub_type： 杂志文章
doi：10.1021/pr4008464
更新日期：2014-02-07 00:00:00
abstract：:Facing the explosion of newly generated protein sequences in the post genomic era, we are challenged to develop an automated method for fast and reliably annotating their subcellular locations. Knowledge of subcellular locations of proteins can provide useful hints for revealing their functions and understanding how t...
journal_title：Journal of proteome research
pub_type： 杂志文章
doi：10.1021/pr060167c
更新日期：2006-08-01 00:00:00
abstract：:We previously described a microLC-ESI-Q-TOF MS method for identifying monoclonal immunoglobulins in serum and then tracking them over time using their accurate molecular mass. Here we demonstrate how the same methodology can be used to identify and characterize polyclonal immunoglobulins in serum. We establish that tw...
journal_title：Journal of proteome research
pub_type： 杂志文章
doi：10.1021/pr5005967
更新日期：2014-11-07 00:00:00
abstract：:Two-dimensional differential gel electrophoresis (2-D DIGE) was used to analyze human serum following the removal of albumin and five other high-abundant serum proteins. After protein removal, serum was analyzed by SDS-PAGE as a preliminary screen, and significant differences between four high-abundant protein removal...
journal_title：Journal of proteome research
pub_type： 杂志文章
doi：10.1021/pr049921p
更新日期：2004-11-01 00:00:00
abstract：:Elevated atmospheric CO2 and nitrogen are major environmental factors affecting shoot growth. The objectives of this study are to determine the interactive effects of elevated CO2 and nitrogen on leaf growth in tall fescue ( Festuca arundinacea) and to identify major proteins and associated metabolic pathways underlyi...
journal_title：Journal of proteome research
pub_type： 杂志文章
doi：10.1021/acs.jproteome.8b00951
更新日期：2019-06-07 00:00:00
abstract：:Candida albicans is a commensal microorganism in the oral cavity and gastrointestinal and urogenital tracts of most individuals that acts as an opportunistic pathogen when the host immune response is reduced. Here, we established different immunocompetent murine models to analyze the antibody responses to the C. albic...
journal_title：Journal of proteome research
pub_type： 杂志文章
doi：10.1021/acs.jproteome.6b00383
更新日期：2017-01-06 00:00:00
abstract：:Protein phosphorylation is a major mechanism of signal transduction in bacteria. Here, we analyzed the proteome and phosphoproteome of a wild-type strain of the food-borne pathogen Listeria monocytogenes that was grown in either chemically defined medium or rich medium containing glucose. We then compared these result...
journal_title：Journal of proteome research
pub_type： 杂志文章
doi：10.1021/pr500929u
更新日期：2014-12-05 00:00:00
abstract：:Glycans play major roles in living organisms. Thus, essential information is required on diverse glycans, their location, and moieties in proteins, as well as for technology in a high-throughput manner, for improving functional glycomics. In the present study, we describe a new approach involving a 2-D array, which ha...
journal_title：Journal of proteome research
pub_type： 杂志文章
doi：10.1021/pr070392+
更新日期：2008-03-01 00:00:00
abstract：:Francisella tularensis is a Gram-negative bacterium that causes the zoonotic disease tularemia. The historical development of tularemia as a biological weapon has led to it being characterized by the CDC as a category A biothreat agent. Neither posttranslational modification (PTM) of proteins, in particular lysine ace...
journal_title：Journal of proteome research
pub_type： 杂志文章
doi：10.1021/acs.jproteome.9b00512
更新日期：2020-04-03 00:00:00
abstract：:Correct phosphorylation site assignment is a critical aspect of phosphoproteomic analysis. Large-scale phosphopeptide data sets that are generated through liquid chromatography-coupled tandem mass spectrometry (LC-MS/MS) analysis often contain hundreds or thousands of phosphorylation sites that require validation. To ...
journal_title：Journal of proteome research
pub_type： 杂志文章
doi：10.1021/pr800169k
更新日期：2008-07-01 00:00:00
abstract：:Rheumatoid arthritis is a progressive, highly debilitating disease where early diagnosis, enabling rapid clinical intervention, would provide obvious benefits to patients, healthcare systems, and society. Novel biomarkers that enable noninvasive early diagnosis of the onset and progression of the disease provide one r...
journal_title：Journal of proteome research
pub_type： 杂志文章
doi：10.1021/acs.jproteome.6b00654
更新日期：2016-12-02 00:00:00
abstract：:Recent physiological studies indicated that S. lividans metabolism was mainly glycolytic, whereas S. coelicolor metabolism was mainly oxidative. To determine whether such metabolic characteristics were correlated with consistent proteomics features, a comparative label-free, shotgun proteomics analysis of these strain...
journal_title：Journal of proteome research
pub_type： 杂志文章
doi：10.1021/acs.jproteome.7b00163
更新日期：2017-07-07 00:00:00
abstract：:Transient cerebral ischemia dramatically activates small ubiquitin-like modifier (SUMO2/3) conjugation. In cells exposed to 6 h of transient oxygen/glucose deprivation (OGD), a model of ischemia, SUMOylation increases profoundly between 0 and 30 min following re-oxygenation. To elucidate the effect of transient OGD on...
journal_title：Journal of proteome research
pub_type： 杂志文章
doi：10.1021/pr200834f
更新日期：2012-02-03 00:00:00
abstract：:In this study we selected three breast cancer cell lines (SKBR3, SUM149 and SUM190) with different oncogene expression levels involved in ERBB2 and EGFR signaling pathways as a model system for the evaluation of selective integration of subsets of transcriptomic and proteomic data. We assessed the oncogene status with...
journal_title：Journal of proteome research
pub_type： 杂志文章
doi：10.1021/pr4001527
更新日期：2013-06-07 00:00:00
