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Post translational modifications

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https://www.readbyqxmd.com/read/28813682/circadian-and-feeding-rhythms-orchestrate-the-diurnal-liver-acetylome
#1
Daniel Mauvoisin, Florian Atger, Loïc Dayon, Antonio Núñez Galindo, Jingkui Wang, Eva Martin, Laetitia Da Silva, Ivan Montoliu, Sebastiano Collino, Francois-Pierre Martin, Joanna Ratajczak, Carles Cantó, Martin Kussmann, Felix Naef, Frédéric Gachon
Lysine acetylation is involved in various biological processes and is considered a key reversible post-translational modification in the regulation of gene expression, enzyme activity, and subcellular localization. This post-translational modification is therefore highly relevant in the context of circadian biology, but its characterization on the proteome-wide scale and its circadian clock dependence are still poorly described. Here, we provide a comprehensive and rhythmic acetylome map of the mouse liver...
August 15, 2017: Cell Reports
https://www.readbyqxmd.com/read/28813517/prmepred-a-protein-arginine-methylation-prediction-tool
#2
Pawan Kumar, Joseph Joy, Ashutosh Pandey, Dinesh Gupta
Protein methylation is an important Post-Translational Modification (PTMs) of proteins. Arginine methylation carries out and regulates several important biological functions, including gene regulation and signal transduction. Experimental identification of arginine methylation site is a daunting task as it is costly as well as time and labour intensive. Hence reliable prediction tools play an important task in rapid screening and identification of possible methylation sites in proteomes. Our preliminary assessment using the available prediction methods on collected data yielded unimpressive results...
2017: PloS One
https://www.readbyqxmd.com/read/28812749/radical-driven-processes-within-a-peptidic-sequence-of-type-i-collagen-upon-single-photon-ionisation-in-the-gas-phase
#3
Lucas Schwob, Mathieu Lalande, Dmitrii Egorov, Jimmy Rangama, Ronnie Hoekstra, Violaine Vizcaino, Thomas Schlathölter, Jean-Christophe Poully
We report on an experimental single-photon absorption study on gas-phase protonated collagen peptides employing a combination of mass spectrometry and synchrotron radiation. Partial ion yields for the main photoabsorption products vary steadily with photon energy over the range from 14 to 545 eV. At low energy, non-dissociative photoionisation competes with neutral molecule loss from the precursor ion, whereas fragmentation of the peptide backbone dominates at soft X-ray energies. Neutral molecule losses from the ionised peptide are found to have low energy barriers and most likely involve amino-acid residue side-chains with radical character, in particular aspartic acid...
August 16, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28812241/plasma-glycoproteomic-study-of-therapeutic-hypothermia-reveals-novel-markers-predicting-neurologic-outcome-post-cardiac-arrest
#4
Wenjun Deng, Jing Cao, Lei Chen, David McMullin, James L Januzzi, Ferdinando S Buonanno, Eng H Lo, MingMing Ning
Therapeutic hypothermia (TH) is a neuroprotective treatment post-cardiac arrest but is grossly underutilized. After TH induction, traditional biomarkers and parameters can no long predict clinical outcome due to a lack of understanding of hypothermic response. Innovative approaches to better understand the clinical effect of TH will help to prognosticate outcome and expand beneficial population. Protein glycosylation is an important extracellular post-translational modification, regulating various extracellular signaling pathways...
August 15, 2017: Translational Stroke Research
https://www.readbyqxmd.com/read/28810660/recent-advancements-in-understanding-mammalian-o-mannosylation
#5
M Osman Sheikh, Stephanie M Halmo, Lance Wells
The post-translational glycosylation of select proteins by O-linked mannose (O-mannose or O-man) is a conserved modification from yeast to humans and has been shown to be necessary for proper development and growth. The most well studied O-mannosylated mammalian protein is α-dystroglycan (α-DG). Hypoglycosylation of α-DG results in varying severities of congenital muscular dystrophies, cancer progression and metastasis, and inhibited entry and infection of certain arenaviruses. Defects in the gene products responsible for post-translational modification of α-DG, primarily glycosyltransferases, are the basis for these diseases...
September 1, 2017: Glycobiology
https://www.readbyqxmd.com/read/28809825/analysis-of-histone-antibody-specificity-with-peptide-microarrays
#6
Evan M Cornett, Bradley M Dickson, Scott B Rothbart
Post-translational modifications (PTMs) on histone proteins are widely studied for their roles in regulating chromatin structure and gene expression. The mass production and distribution of antibodies specific to histone PTMs has greatly facilitated research on these marks. As histone PTM antibodies are key reagents for many chromatin biochemistry applications, rigorous analysis of antibody specificity is necessary for accurate data interpretation and continued progress in the field. This protocol describes an integrated pipeline for the design, fabrication and use of peptide microarrays for profiling the specificity of histone antibodies...
August 1, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28809486/assembling-glycan-charged-dolichol-phosphates-chemoenzymatic-synthesis-of-a-haloferax-volcanii-n-glycosylation-pathway-intermediate
#7
Yifat Elharar, Ananda R Podilapu, Ziqiang Guan, Suvarn S Kulkarni, Jerry Eichler
N-glycosylation, the covalent attachment of glycans to select protein target Asn residues, is a post-translational modification performed by all three domains of life. In the halophilic archaea Haloferax volcanii, where understanding of this universal protein-processing event is relatively well-advanced, genes encoding the components of the Agl (archaeal glycosylation) pathway responsible for the assembly and attachment of an N-linked pentasaccharide have been identified. As elsewhere, the N-linked glycan is assembled on phosphodolichol carriers before transfer to target Asn residues...
August 15, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28809078/profiling-protein-s-sulfination-with-maleimide-linked-probes
#8
Yu-Hsuan Kuo, Aaron M Konopko, Nicholas B Borotto, Jaimeen D Majmudar, Sarah E Haynes, Brent R Martin
Cysteine residues are susceptible to oxidation to form S-sulfinyl (R-SO2H) and S-sulfonyl (R-SO3H) post-translational modifications. Here we present a simple bioconjugation strategy to label S-sulfinated proteins using reporter-linked maleimides. After alkylation of free thiols with iodoacetamide, S-sulfinated cysteines react with maleimide to form a sulfone Michael adduct that remains stable under acidic conditions. Using this sequential alkylation strategy, we demonstrate differential S-sulfination across mouse tissue homogenates, as well as enhanced S-sulfination following pharmacological induction of ER stress, lipopolysaccharide stimulation, and inhibitors of the electron transport chain...
August 14, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/28809000/post-translational-modification-profiling-functional-proteomics-for-the-analysis-of-immune-regulation
#9
Avital Eisenberg-Lerner, Ifat Regev, Yifat Merbl
Posttranslational modifications (PTMs) of proteins are an integral part of major cellular regulatory mechanisms dictating protein function, localization, and stability. The capacity to screen PTMs using protein microarrays has advanced our ability to identify their targets and regulatory role. This chapter discusses a unique procedure that combines functional extract-based activity assay with large-scale screening utilities of protein microarrays. This "PTM-profiling" system offers advantages in quantitatively identifying modifications in an unbiased manner in the context of specific cellular conditions...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28807942/nuclear-fak-and-runx1-cooperate-to-regulate-igfbp3-cell-cycle-progression-and-tumor-growth
#10
Marta Canel, Adam Byron, Andrew H Sims, Jessy Cartier, Hitesh Patel, Margaret C Frame, Valerie G Brunton, Bryan Serrels, Alan Serrels
Nuclear focal adhesion kinase (FAK) is a potentially important regulator of gene expression in cancer, impacting both cellular function and the composition of the surrounding tumor microenvironment. Here we report in a murine model of skin squamous cell carcinoma (SCC) that nuclear FAK regulates Runx1-dependent transcription of insulin-like growth factor binding protein 3 (IGFBP3), and that this regulates SCC cell cycle progression and tumor growth in vivo. Furthermore, we identified a novel molecular complex between FAK and Runx1 in the nucleus of SCC cells and showed that FAK interacted with a number of Runx1 regulatory proteins, including Sin3a and other epigenetic modifiers known to alter Runx1 transcriptional function through post-translational modification...
August 14, 2017: Cancer Research
https://www.readbyqxmd.com/read/28806398/lysine-52-stabilizes-the-myc-oncoprotein-through-an-scf-fbxw7-independent-mechanism
#11
J De Melo, S S Kim, C Lourenco, L Z Penn
The oncogenic transcription factor c-MYC (MYC) is deregulated and often overexpressed in more than 50% of cancers. MYC deregulation is associated with poor prognosis and aggressive disease, suggesting that the development of therapeutic inhibitors targeting MYC would markedly impact patient outcome. MYC is highly regulated, with a protein and mRNA half-life of ~30 min. The most extensively studied pathway regulating MYC protein stability involves ubiquitylation and proteasomal degradation mediated by the E3-ligase, SCF(Fbxw7)...
August 14, 2017: Oncogene
https://www.readbyqxmd.com/read/28806136/harnessing-olig2-function-in-tumorigenicity-and-plasticity-to-target-malignant-gliomas
#12
Jennifer Kosty, Fanghui Lu, Robert Kupp, Shwetal Mehta, Q Richard Lu
Glioblastoma (GBM) is the most prevalent and malignant brain tumor, displaying notorious resistance to conventional therapy, partially due to molecular and genetic heterogeneity. Understanding the mechanisms for gliomagenesis, tumor stem/progenitor cell propagation and phenotypic diversity is critical for devising effective and targeted therapy for this lethal disease. The basic helix-loop-helix transcription factor OLIG2, which is universally expressed in gliomas, has emerged as an important player in GBM cell reprogramming, genotoxic resistance, and tumor phenotype plasticity...
August 14, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28805808/constraints-and-consequences-of-the-emergence-of-amino-acid-repeats-in-eukaryotic-proteins
#13
Sreenivas Chavali, Pavithra L Chavali, Guilhem Chalancon, Natalia Sanchez de Groot, Rita Gemayel, Natasha S Latysheva, Elizabeth Ing-Simmons, Kevin J Verstrepen, Santhanam Balaji, M Madan Babu
Proteins with amino acid homorepeats have the potential to be detrimental to cells and are often associated with human diseases. Why, then, are homorepeats prevalent in eukaryotic proteomes? In yeast, homorepeats are enriched in proteins that are essential and pleiotropic and that buffer environmental insults. The presence of homorepeats increases the functional versatility of proteins by mediating protein interactions and facilitating spatial organization in a repeat-dependent manner. During evolution, homorepeats are preferentially retained in proteins with stringent proteostasis, which might minimize repeat-associated detrimental effects such as unregulated phase separation and protein aggregation...
August 14, 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28804911/chronic-ethanol-metabolism-inhibits-hepatic-mitochondrial-superoxide-dismutase-via-lysine-acetylation
#14
Mohammed A Assiri, Samantha R Roy, Peter S Harris, Hadi Ali, Yongliang Liang, Colin T Shearn, David J Orlicky, James R Roede, Matthew D Hirschey, Donald S Backos, Kristofer S Fritz
BACKGROUND: Chronic ethanol consumption is a major cause of liver disease worldwide. Oxidative stress is a known consequence of ethanol metabolism and is thought to contribute significantly to alcoholic liver disease (ALD). Therefore, elucidating pathways leading to sustained oxidative stress and downstream redox imbalances may reveal how ethanol consumption leads to ALD. Recent studies suggest that ethanol metabolism impacts mitochondrial antioxidant processes through a number of proteomic alterations, including hyperacetylation of key antioxidant proteins...
August 14, 2017: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/28804462/heat-acclimation-mediated-cross-tolerance-origins-in-within-life-epigenetics
#15
REVIEW
Michal Horowitz
The primary outcome of heat acclimation is increased thermotolerance, which stems from enhancement of innate cytoprotective pathways. These pathways produce "ON CALL" molecules that can combat stressors to which the body has never been exposed, via cross-tolerance mechanisms (heat acclimation-mediated cross-tolerance-HACT). The foundation of HACT lies in the sharing of generic stress signaling, combined with tissue/organ- specific protective responses. HACT becomes apparent when acclimatory homeostasis is achieved, lasts for several weeks, and has a memory...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28803690/new-insights-into-non-conventional-epitopes-as-t-cell-targets-the-missing-link-for-breaking-immune-tolerance-in-autoimmune-disease
#16
REVIEW
James Harbige, Martin Eichmann, Mark Peakman
The mechanism by which immune tolerance is breached in autoimmune disease is poorly understood. One possibility is that post-translational modification of self-antigens leads to peripheral recognition of neo-epitopes against which central and peripheral tolerance is inadequate. Accumulating evidence points to multiple mechanisms through which non-germline encoded sequences can give rise to these non-conventional epitopes which in turn engage the immune system as T cell targets. In particular, where these modifications alter the rules of epitope engagement with MHC molecules, such non-conventional epitopes offer a persuasive explanation for associations between specific HLA alleles and autoimmune diseases...
August 10, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28803438/inhibitor-of-endocannabinoid-deactivation-protects-against-in-vitro-and-in-vivo-neurotoxic-effects-of-paraoxon
#17
Karen L G Farizatto, Sara A McEwan, Vinogran Naidoo, Spyros P Nikas, Vidyanand G Shukla, Michael F Almeida, Aaron Byrd, Heather Romine, David A Karanian, Alexandros Makriyannis, Ben A Bahr
The anticholinesterase paraoxon (Pxn) is related to military nerve agents that increase acetylcholine levels, trigger seizures, and cause excitotoxic damage in the brain. In rat hippocampal slice cultures, high-dose Pxn was applied resulting in a presynaptic vulnerability evidenced by a 64% reduction in synapsin IIb (syn IIb) levels, whereas the postsynaptic protein GluR1 was unchanged. Other signs of Pxn-induced cytotoxicity include the oxidative stress-related production of stable 4-hydroxynonenal (4-HNE)-protein adducts...
August 12, 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/28802644/rapid-characterization-of-the-cho-platform-cell-line-and-identification-of-pseudo-attp-sites-for-phic31-integrase
#18
Narges Damavandi, Mozhgan Raigani, Atefeh Joudaki, Fatemeh Davami, Sirous Zeinali
The Chinese Hamster Ovary (CHO) cell lines, applicable to post-translational modifications, are preferred systems for biopharmaceutical protein production. In this study, by using the Jump-In™ TI™ technology which employs PhiC31 and R4 bacteriophage recombinases, a platform CHO-K1 cell line containing a R4-attP site was generated. Here, a combination of Quantitative Fluorescent-Polymerase Chain Reaction (QF-PCR) and semi-random, two-step PCR (ST-PCR), was performed to feature the platform cell clones. Our results show that QF-PCR and ST-PCR, can be utilized for efficient and accelerated cell line characterization...
August 9, 2017: Protein Expression and Purification
https://www.readbyqxmd.com/read/28801661/statistical-characterization-of-therapeutic-protein-modifications
#19
Tsung-Heng Tsai, Zhiqi Hao, Qiuting Hong, Benjamin Moore, Cinzia Stella, Jeffrey H Zhang, Yan Chen, Michael Kim, Theo Koulis, Gregory A Ryslik, Erik Verschueren, Fred Jacobson, William E Haskins, Olga Vitek
Peptide mapping with liquid chromatography-tandem mass spectrometry (LC-MS/MS) is an important analytical method for characterization of post-translational and chemical modifications in therapeutic proteins. Despite its importance, there is currently no consensus on the statistical analysis of the resulting data. In this manuscript, we distinguish three statistical goals for therapeutic protein characterization: (1) estimation of site occupancy of modifications in one condition, (2) detection of differential site occupancy between conditions, and (3) estimation of combined site occupancy across multiple modification sites...
August 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28801655/%C3%AE-1-adrenergic-receptor-o-glycosylation-regulates-n-terminal-cleavage-and-signaling-responses-in-cardiomyocytes
#20
Misun Park, Gopireddy R Reddy, Gerd Wallukat, Yang K Xiang, Susan F Steinberg
β1-adrenergic receptors (β1ARs) mediate catecholamine actions in cardiomyocytes by coupling to both Gs/cAMP-dependent and Gs-independent/growth-regulatory pathways. Structural studies of the β1AR define ligand-binding sites in the transmembrane helices and effector docking sites at the intracellular surface of the β1AR, but the extracellular N-terminus, which is a target for post-translational modifications, typically is ignored. This study identifies β1AR N-terminal O-glycosylation at Ser(37)/Ser(41) as a mechanism that prevents β1AR N-terminal cleavage...
August 11, 2017: Scientific Reports
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