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https://www.readbyqxmd.com/read/29161012/top-down-proteomics-ready-for-prime-time
#1
Bifan Chen, Kyle A Brown, Ziqing Lin, Ying Ge
In the post-genomics era, the study of proteins is critical for understanding cellular functions at the molecular level.1-5 Beyond the genetic code, the human proteome is greatly diversified by various genetic variations, alternative splicing of RNA transcripts, and post-translational modifi-cations (PTMs).6,7 In 2013, the term "proteoform" was designated to describe "all of the different molecular forms in which the protein product of a single gene can be found",6 clearing up the confusion in nomenclature and joining research efforts to develop methodologies for pro-teoform characterization...
November 21, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/29157277/a-validated-antibody-panel-for-the-characterization-of-tau-post-translational-modifications
#2
Ebru Ercan, Sameh Eid, Christian Weber, Alexandra Kowalski, Maria Bichmann, Annika Behrendt, Frank Matthes, Sybille Krauss, Peter Reinhardt, Simone Fulle, Dagmar E Ehrnhoefer
BACKGROUND: Tau is a microtubule-binding protein, which is subject to various post-translational modifications (PTMs) including phosphorylation, methylation, acetylation, glycosylation, nitration, sumoylation and truncation. Aberrant PTMs such as hyperphosphorylation result in tau aggregation and the formation of neurofibrillary tangles, which are a hallmark of Alzheimer's disease (AD). In order to study the importance of PTMs on tau function, antibodies raised against specific modification sites are widely used...
November 21, 2017: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/29157087/thanatos-an-integrative-data-resource-of-proteins-and-post-translational-modifications-in-the-regulation-of-autophagy
#3
Wankun Deng, Lili Ma, Ying Zhang, Jiaqi Zhou, Yongbo Wang, Zexian Liu, Yu Xue
Macroautophagy/autophagy is a highly conserved process for degrading cytoplasmic contents, determines cell survival or death, and regulates the cellular homeostasis. Besides ATG proteins, numerous regulators together with various post-translational modifications (PTMs) are also involved in autophagy. In this work, we collected 4,237 experimentally identified proteins regulated in autophagy and cell death pathways from the literature. Then we computationally identified potential orthologs of known proteins, and developed a comprehensive database of The Autophagy, Necrosis, ApopTosis OrchestratorS (THANATOS, http://thanatos...
November 20, 2017: Autophagy
https://www.readbyqxmd.com/read/29145615/iptmnet-an-integrated-resource-for-protein-post-translational-modification-network-discovery
#4
Hongzhan Huang, Cecilia N Arighi, Karen E Ross, Jia Ren, Gang Li, Sheng-Chih Chen, Qinghua Wang, Julie Cowart, K Vijay-Shanker, Cathy H Wu
Protein post-translational modifications (PTMs) play a pivotal role in numerous biological processes by modulating regulation of protein function. We have developed iPTMnet (http://proteininformationresource.org/iPTMnet) for PTM knowledge discovery, employing an integrative bioinformatics approach-combining text mining, data mining, and ontological representation to capture rich PTM information, including PTM enzyme-substrate-site relationships, PTM-specific protein-protein interactions (PPIs) and PTM conservation across species...
November 14, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29142256/quantitative-analysis-of-protein-protein-interactions-and-post-translational-modifications-in-rare-immune-populations
#5
Ayelet Avin, Maayan Levy, Ziv Porat, Jakub Abramson
In spite of recent advances in proteomics, quantitative analyses of protein-protein interactions (PPIs) or post-translational modifications (PTMs) in rare cell populations remain challenging. This is in particular true for analyses of rare immune and/or stem cell populations that are directly isolated from humans or animal models, and which are often characterized by multiple surface markers. To overcome these limitations, here we have developed proximity ligation imaging cytometry (PLIC), a protocol for proteomic analysis of rare cells...
November 15, 2017: Nature Communications
https://www.readbyqxmd.com/read/29142126/hpv-replication-regulation-by-acetylation-of-a-conserved-lysine-in-the-e2-protein
#6
Yanique Thomas, Elliot J Androphy
The Papillomavirus (PV) E2 protein is a sequence specific DNA binding protein that recruits cellular factors to its genome in infected epithelial cells. E2 also binds to and loads the viral E1 DNA helicase at the origin of replication. Post-translational modifications (PTMs) of PV E2 have been identified as potential regulators E2 functions. We recently reported lysine (K) 111 as a target of p300 acetylation in bovine (B)PV. The di-lysines at 111 and 112 are conserved in almost all papillomaviruses. We pursued a mutational approach to query the functional significance of lysine in human (H)PV E2...
November 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29133298/functional-redundancy-of-variant-and-canonical-histone-h3-lysine-9-modification-in-drosophila
#7
Taylor J R Penke, Daniel J McKay, Brian D Strahl, A Gregory Matera, Robert J Duronio
Histone post-translational modifications (PTMs) and differential incorporation of variant and canonical histones into chromatin are central modes of epigenetic regulation. Despite similar protein sequences, histone variants are enriched for different suites of PTMs compared to their canonical counterparts. For example, variant histone H3.3 occurs primarily in transcribed regions and is enriched for "active" histone PTMs like Lys9 acetylation (H3.3K9ac), whereas the canonical histone H3 is enriched for Lys9 methylation (H3K9me), which is found in transcriptionally silent heterochromatin...
November 13, 2017: Genetics
https://www.readbyqxmd.com/read/29133117/application-of-mixed-peptide-arrays-to-study-combinatorial-readout-of-chromatin-modifications
#8
Rebekka Mauser, Goran Kungulovski, David Meral, Daniel Maisch, Albert Jeltsch
The N-terminal tails of histone proteins are massively decorated with post-translational modifications (PTMs), which play important roles in the regulation of gene expression. Several highly conserved chromatin interacting proteins can bind to histone modifications in a sequence and modification specific manner employing specific reading domains. These proteins often contain several reading domains, which can cooperate in the readout of different PTMs. To gain a better insight into the combinatorial readout of PTMs, we developed a method to study the binding of double reading domains to mixed peptide arrays containing two different peptides in each spot...
November 10, 2017: Biochimie
https://www.readbyqxmd.com/read/29132214/chemical-probes-for-redox-signaling-and-oxidative-stress
#9
Masahiro Abo, Eranthie Weerapana
SIGNIFICANCE: Cellular reactive oxygen species (ROS) mediate redox signaling cascades that are critical to numerous physiological and pathological processes. Analytical methods to monitor cellular ROS levels and proteomic platforms to identify oxidative post-translational modifications (PTMs) of proteins are critical to understanding the triggers and consequences of redox signaling. Recent advances: The prevalence and significance of redox signaling has recently been illuminated through the use of chemical probes that allow for sensitive detection of cellular ROS levels and proteomic dissection of oxidative PTMs directly in living cells...
November 13, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/29129530/glutamylation-regulates-transport-specializes-function-and-sculpts-the-structure-of-cilia
#10
Robert O'Hagan, Malan Silva, Ken C Q Nguyen, Winnie Zhang, Sebastian Bellotti, Yasmin H Ramadan, David H Hall, Maureen M Barr
Ciliary microtubules (MTs) are extensively decorated with post-translational modifications (PTMs), such as glutamylation of tubulin tails. PTMs and tubulin isotype diversity act as a "tubulin code" that regulates cytoskeletal stability and the activity of MT-associated proteins such as kinesins. We previously showed that, in C. elegans cilia, the deglutamylase CCPP-1 affects ciliary ultrastructure, localization of the TRP channel PKD-2 and the kinesin-3 KLP-6, and velocity of the kinesin-2 OSM-3/KIF17, whereas a cell-specific α-tubulin isotype regulates ciliary ultrastructure, intraflagellar transport, and ciliary functions of extracellular vesicle (EV)-releasing neurons...
November 20, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/29126343/oxidative-stress-triggered-interactions-between-the-succinyl-and-acetyl-proteomes-of-rice-leaves
#11
Heng Zhou, Iris Finkemeier, Wenxue Guan, Maria-Armineh Tossounian, Bo Wei, David Young, Jingjing Huang, Joris Messens, Xibin Yang, Jun Zhu, Michael H Wilson, Wenbiao Shen, Yanjie Xie, Christine H Foyer
Protein lysine acylations, such as succinylation and acetylation are important posttranslational modification (PTM) mechanisms, with key roles in cellular regulation. Antibody-based affinity enrichment, high-resolution LC-MS/MS analysis and integrated bioinformatics analysis were used to characterize the lysine succinylome (Ksuc ) and acetylome (Kace ) of rice leaves. In total, 2593 succinylated and 1024 acetylated proteins were identified, of which 723 were simultaneously acetylated and succinylated. Proteins involved in photosynthetic carbon metabolism such as the large and small subunits of RuBisCO, ribosomal functions and other key processes were subject to both PTMs...
November 10, 2017: Plant, Cell & Environment
https://www.readbyqxmd.com/read/29126202/activedriverdb-human-disease-mutations-and-genome-variation-in-post-translational-modification-sites-of-proteins
#12
Michal Krassowski, Marta Paczkowska, Kim Cullion, Tina Huang, Irakli Dzneladze, B F Francis Ouellette, Joseph T Yamada, Amelie Fradet-Turcotte, Jüri Reimand
Interpretation of genetic variation is needed for deciphering genotype-phenotype associations, mechanisms of inherited disease, and cancer driver mutations. Millions of single nucleotide variants (SNVs) in human genomes are known and thousands are associated with disease. An estimated 21% of disease-associated amino acid substitutions corresponding to missense SNVs are located in protein sites of post-translational modifications (PTMs), chemical modifications of amino acids that extend protein function. ActiveDriverDB is a comprehensive human proteo-genomics database that annotates disease mutations and population variants through the lens of PTMs...
November 8, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29121770/assessment-of-quantification-precision-of-histone-post-translational-modifications-by-using-an-ion-trap-and-down-to-50%C3%A2-000-cells-as-starting-material
#13
Qi Guo, Simone Sidoli, Benjamin A Garcia, Xiaolu Zhao
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-throughput quantification of hundreds of histone PTMs. Samples such as primary tissues, complex model systems, and biofluids are hard to retrieve in large quantities. Because of this, it is critical to know whether the amount of sample available would lead to an exhaustive analysis if subjected to MS...
November 21, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/29118029/giapronto-a-one-click-graph-visualization-software-for-proteomics-datasets
#14
Amber Kathryn Weiner, Simone Sidoli, Sharon J Diskin, Ben Garcia
Here we present a free interactive web tool to process and visualize proteomics datasets with a single click. GiaPronto can process all proteomics quantification methods, i.e. label-free, SILAC and isobaric labeling, and analyze post-translational modifications (PTMs). The software performs normalization and statistics, assists determination of regulated proteins, biomarkers and Gene Ontology (GO) enrichment, and provides high resolution images and tables for further data analysis. We foresee that GiaPronto will become the most rapid and simple tool for assessing data quality and determining most relevant features of proteomic datasets...
November 8, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/29111742/increased-post-translational-lysine-acetylation-of-myelin-basic-protein-is-associated-with-peak-neurological-disability-in-a-mouse-experimental-autoimmune-encephalomyelitis-model-of-multiple-sclerosis
#15
Ryan Lillico, Ting Zhou, Tina Khorshid Ahmad, Nicholas Stesco, Kiana Gozda, Jessica Truong, Jiming Kong, Ted M Lakowski, Michael Namaka
Citrullination of arginine residues is a post-translational modification (PTM) found on myelin basic protein (MBP), which neutralizes MBPs positive charge, and is implicated in myelin damage and multiple sclerosis (MS). Here we identify lysine acetylation as another neutralizing PTM to MBP that may be involved in myelin damage. We quantify changes in lysine and arginine PTMs on MBP derived from mice induced with an experimental autoimmune encephalomyelitis (EAE) model of MS using liquid chromatography tandem mass spectrometry...
November 7, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/29109951/rna-binding-protein-regulation-and-cross-talk-in-the-control-of-au-rich-mrna-fate
#16
REVIEW
Sofía M García-Mauriño, Francisco Rivero-Rodríguez, Alejandro Velázquez-Cruz, Marian Hernández-Vellisca, Antonio Díaz-Quintana, Miguel A De la Rosa, Irene Díaz-Moreno
mRNA metabolism is tightly orchestrated by highly-regulated RNA Binding Proteins (RBPs) that determine mRNA fate, thereby influencing multiple cellular functions across biological contexts. Here, we review the interplay between six well-known RBPs (TTP, AUF-1, KSRP, HuR, TIA-1, and TIAR) that recognize AU-rich elements (AREs) at the 3' untranslated regions of mRNAs, namely ARE-RBPs. Examples of the links between their cross-regulations and modulation of their targets are analyzed during mRNA processing, turnover, localization, and translational control...
2017: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/29101055/detection-of-post-translational-modifications-using-solid-phase-proximity-ligation-assay
#17
Felipe Marques Souza de Oliveira, Stefan Mereiter, Peter Lönn, Benjamin Siart, Qiujin Shen, Johan Heldin, Doroteya Raykova, Niclas Karlsson, Karol Polom, Franco Roviello, Celso A Reis, Masood Kamali-Moghaddam
Post-translational modifications (PTMs) regulate protein activities to help orchestrate and fine-tune cellular processes. Dysregulation of PTMs is often related with disorders and malignancies, and may serve as a precise biomarker of disease. Developing sensitive tools to measure and monitor low-abundant PTMs in tissue lysates or serum will be instrumental for opening up new PTM-based diagnostic avenues. Here, we investigate the use of solid-phase proximity ligation assay (SP-PLA) for detection of different PTMs...
October 31, 2017: New Biotechnology
https://www.readbyqxmd.com/read/29100108/complex-regulatory-mechanisms-mediated-by-the-interplay-of-multiple-post-translational-modifications
#18
REVIEW
Veronika Csizmok, Julie D Forman-Kay
Post-translational modifications (PTMs), which are found largely in intrinsically disordered protein regions (IDRs), regulate protein activity, stability and interactions with partners. They are therefore critical for controlling essentially all cellular processes. A single modification event can have dramatic effects; however, proteins are often modified on multiple sites to collectively modulate the biological outcome. Multiple PTMs can mediate the same, complementary or opposing effects and the result of their interplay is determined by a complex combination of the number, positioning and type of modifications...
November 5, 2017: Current Opinion in Structural Biology
https://www.readbyqxmd.com/read/29099585/a-sweet-embrace-control-of-protein-protein-interactions-by-o-linked-%C3%AE-n-acetylglucosamine
#19
Heather J Tarbet, Clifford A Toleman, Michael Boyce
O-linked β-N-acetylglucosamine (O-GlcNAc) is a critical post-translational modification (PTM) of thousands of intracellular proteins. Reversible O-GlcNAcylation governs many aspects of cell physiology and is dysregulated in numerous human diseases. Despite this broad pathophysiological significance, major aspects of O-GlcNAc signaling remain poorly understood, including the biochemical mechanisms through which O-GlcNAc transduces information. Recent work from many labs, including our own, has revealed that O-GlcNAc, like other intracellular PTMs, can control its substrates' functions by inhibiting or inducing protein-protein interactions...
November 3, 2017: Biochemistry
https://www.readbyqxmd.com/read/29098080/methylation-of-transcription-factor-yy2-regulates-its-transcriptional-activity-and-cell-proliferation
#20
Xiao-Nan Wu, Tao-Tao Shi, Yao-Hui He, Fei-Fei Wang, Rui Sang, Jian-Cheng Ding, Wen-Juan Zhang, Xing-Yi Shu, Hai-Feng Shen, Jia Yi, Xiang Gao, Wen Liu
Yin Yang 1 (YY1) is a multifunctional DNA-binding transcription factor shown to be critical in a variety of biological processes, and its activity and function have been shown to be regulated by multitude of mechanisms, which include but are not limited to post-translational modifications (PTMs), its associated proteins and cellular localization. YY2, the paralog of YY1 in mouse and human, has been proposed to function redundantly or oppositely in a context-specific manner compared with YY1. Despite its functional importance, how YY2's DNA-binding activity and function are regulated, particularly by PTMs, remains completely unknown...
2017: Cell Discovery
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