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Post translational modification

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https://www.readbyqxmd.com/read/28544119/common-fibril-structures-imply-systemically-conserved-protein-misfolding-pathways-in%C3%A2-vivo
#1
Karthikeyan Annamalai, Falk Liberta, Marie-Theres Vielberg, William Close, Hauke Lilie, Karl-Heinz Gührs, Angelika Schierhorn, Rolf Koehler, Andreas Schmidt, Christian Haupt, Ute Hegenbart, Stefan Schönland, Matthias Schmidt, Michael Groll, Marcus Fändrich
Systemic amyloidosis is caused by the misfolding of a circulating amyloid precursor protein and the deposition of amyloid fibrils in multiple organs. Chemical and biophysical analysis of amyloid fibrils from human AL and murine AA amyloidosis reveal the same fibril morphologies in different tissues or organs of one patient or diseased animal. The observed structural similarities concerned the fibril morphology, the fibril protein primary and secondary structures, the presence of post-translational modifications and, in case of the AL fibrils, the partially folded characteristics of the polypeptide chain within the fibril...
May 23, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28542436/stress-induced-release-of-oct-1-from-the-nuclear-envelope-is-mediated-by-jnk-phosphorylation-of-lamin-b1
#2
Ivan I Boubriak, Ashraf N Malhas, Marek M Drozdz, Lior Pytowski, David J Vaux
The nuclear lamina can bind and sequester transcription factors (TFs), a function lost if the lamina is abnormal, with missing or mutant lamin proteins. We now show that TF sequestration is not all-or-nothing, but a dynamic physiological response to external signals. We show that the binding of the ubiquitous TF, Oct-1, to lamin B1 was reversed under conditions of cellular stress caused, inter alia, by the chemical methylating agent methylmethanesulfonate (MMS). A search for lamin B1 post-translational modifications that might mediate changes in Oct-1 binding using kinase inhibitors uncovered a role for c-Jun N-terminal kinase (JNK)...
2017: PloS One
https://www.readbyqxmd.com/read/28542143/dna-damage-and-s-phase-dependent-e2f1-stabilization-requires-the-ciap1-e3-ubiquitin-ligase-and-is-associated-with-k63-poly-ubiquitination-on-lysine-161-164-residues
#3
Valérie Glorian, Jennifer Allègre, Jean Berthelet, Baptiste Dumetier, Pierre-Marie Boutanquoi, Nathalie Droin, Cémile Kayaci, Jessy Cartier, Simon Gemble, Guillaume Marcion, Daniel Gonzalez, Romain Boidot, Carmen Garrido, Olivier Michaud, Eric Solary, Laurence Dubrez
The E2F transcription factor 1 is subtly regulated along the cell cycle progression and in response to DNA damage by post-translational modifications. Here, we demonstrated that the E3-ubiquitin ligase cellular inhibitor of apoptosis 1 (cIAP1) increases E2F1 K63-poly-ubiquitination on the lysine residue 161/164 cluster, which is associated with the transcriptional factor stability and activity. Mutation of these lysine residues completely abrogates the binding of E2F1 to CCNE, TP73 and APAF1 promoters, thus inhibiting transcriptional activation of these genes and E2F1-mediated cell proliferation control...
May 25, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28541504/e3-ubiquitin-ligases-ubiquitous-actors-in-plant-development-and-abiotic-stress-responses
#4
Kai Shu, Wenyu Yang
Understanding the precise regulatory mechanisms of plant development and stress responses at the post-translational level is currently a topic of intensive research. Protein ubiquitination, including the sequential performances of ubiquitin-activating (E1), ubiquitin-conjugating (E2) and ubiquitin ligase (E3) enzymes, is a refined post-translational modification ubiquitous in all eukaryotes. Plants are an integral part of our ecosystem and, as sessile organisms, the ability to perceive internal and external signals and to adapt well to various environmental challenges is crucial for their survival...
May 25, 2017: Plant & Cell Physiology
https://www.readbyqxmd.com/read/28539332/identification-and-characterization-of-two-types-of-amino-acid-regulated-acetyltransferases-in-actinobacteria
#5
Yu-Xing Lu, Xin-Xin Liu, Wei-Bin Liu, Bang-Ce Ye
One hundred and fifty GCN5-like acetyltransferases with amino acid-binding (ACT)-GCN5-related N- acetyltransferase (GNAT) domain organization have been identified in actinobacteria. The ACT domain is fused to the GNAT domain, conferring amino acid-induced allosteric regulation to these protein acetyltransferases (AAPatA). Members of the AAPatA family share similar secondary structure and are divided into two groups based on the allosteric ligands of the ACT domain: the asparagine-activated PatA and the cysteine-activated PatA...
May 24, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/28539064/recent-advances-in-applying-mass-spectrometry-and-systems-biology-to-determine-brain-dynamics
#6
Enzo Scifo, Giulio Calza, Martin Fuhrmann, Rabah Soliymani, Marc Baumann, Maciej Lalowski
Neurological disorders encompass various pathologies which disrupt normal brain physiology and function. Poor understanding of their underlying molecular mechanisms and their societal burden argues for the necessity of novel prevention strategies, early diagnostic techniques and alternative treatment options to reduce the scale of their expected increase. Areas Covered: This review scrutinizes mass spectrometry based approaches used to investigate brain dynamics in various conditions, including neurodegenerative and neuropsychiatric disorders...
May 24, 2017: Expert Review of Proteomics
https://www.readbyqxmd.com/read/28538984/accuracy-of-medical-claims-for-identifying-cardiovascular-and-bleeding-events-after-myocardial-infarction-a-secondary-analysis-of-the-translate-acs-study
#7
Patricia O Guimarães, Arun Krishnamoorthy, Lisa A Kaltenbach, Kevin J Anstrom, Mark B Effron, Daniel B Mark, Patrick L McCollam, Linda Davidson-Ray, Eric D Peterson, Tracy Y Wang
Importance: Pragmatic clinical trial designs have proposed the use of medical claims data to ascertain clinical events; however, the accuracy of billed diagnoses in identifying potential events is unclear. Objectives: To compare the 1-year cumulative incidences of events when events were identified by medical claims vs by physician adjudication and to assess the accuracy of bill-identified events using physician adjudication as the criterion standard. Design, Setting, and Participants: This post hoc analysis of a clinical trial assessed the medical claims forms and records for all rehospitalizations at 233 US hospitals within 1 year of the index acute myocardial infarction (MI) of 12 365 patients enrolled in the Treatment With Adenosine Diphosphate Receptor Inhibitors: Longitudinal Assessment of Treatment Patterns and Events After Acute Coronary Syndrome (TRANSLATE-ACS) study between April 1, 2010, and October 31, 2012...
May 24, 2017: JAMA Cardiology
https://www.readbyqxmd.com/read/28538164/post-translational-regulation-of-plant-immunity
#8
REVIEW
John Withers, Xinnian Dong
Plants have evolved multi-layered molecular defense strategies to protect against pathogens. Plant immune signaling largely relies on post-translational modifications (PTMs) to induce rapid alterations of signaling pathways to achieve a response that is appropriate to the type of pathogen and infection pressure. In host cells, dynamic PTMs have emerged as powerful regulatory mechanisms that cells use to adjust their immune response. PTM is also a virulence strategy used by pathogens to subvert host immunity through the activities of effector proteins secreted into the host cell...
May 21, 2017: Current Opinion in Plant Biology
https://www.readbyqxmd.com/read/28537572/understanding-nucleosome-dynamics-and-their-links-to-gene-expression-and-dna-replication
#9
REVIEW
William K M Lai, B Franklin Pugh
Advances in genomics technology have provided the means to probe myriad chromatin interactions at unprecedented spatial and temporal resolution. This has led to a profound understanding of nucleosome organization within the genome, revealing that nucleosomes are highly dynamic. Nucleosome dynamics are governed by a complex interplay of histone composition, histone post-translational modifications, nucleosome occupancy and positioning within chromatin, which are influenced by numerous regulatory factors, including general regulatory factors, chromatin remodellers, chaperones and polymerases...
May 24, 2017: Nature Reviews. Molecular Cell Biology
https://www.readbyqxmd.com/read/28537420/nitration-and-glycation-turn-mature-ngf-into-a-toxic-factor-for-motor-neurons-a-role-for-p75-sup-ntr-sup-and-rage-signaling-in-als
#10
Mi Jin Kim, Marcelo R Vargas, Benjamin A Harlan, Kelby M Killoy, Lauren Ball, Susana Comte-Walters, Monika Gooz, Yasuhiko Yamamoto, Joseph S Beckman, Luis Barbeito, Mariana Pehar
Glycating stress can occur together with oxidative stress during neurodegeneration and contribute to the pathogenic mechanism. Nerve growth factor (NGF) accumulates in several neurodegenerative diseases. Besides promoting survival, NGF can paradoxically induce cell death by signaling through the p75 neurotrophin receptor (p75<sup>NTR</sup>). The ability of NGF to induce cell death is increased by nitration of its tyrosine residues under conditions associated with increased peroxynitrite formation...
May 24, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28537268/global-mapping-of-carm1-substrates-defines-enzyme-specificity-and-substrate-recognition
#11
Evgenia Shishkova, Hao Zeng, Fabao Liu, Nicholas W Kwiecien, Alexander S Hebert, Joshua J Coon, Wei Xu
Protein arginine methyltransferases (PRMTs) introduce arginine methylation, a post-translational modification with the increasingly eminent role in normal physiology and disease. PRMT4 or coactivator-associated arginine methyltransferase 1 (CARM1) is a propitious target for cancer therapy; however, few CARM1 substrates are known, and its mechanism of substrate recognition is poorly understood. Here we employed a quantitative mass spectrometry approach to globally profile CARM1 substrates in breast cancer cell lines...
May 24, 2017: Nature Communications
https://www.readbyqxmd.com/read/28536502/lost-in-translation-defects-in-transfer-rna-modifications-and-neurological-disorders
#12
REVIEW
Andrea Bednářová, Marley Hanna, Isabella Durham, Tara VanCleave, Alexis England, Anathbandhu Chaudhuri, Natraj Krishnan
Transfer RNAs (tRNAs) are key molecules participating in protein synthesis. To augment their functionality they undergo extensive post-transcriptional modifications and, as such, are subject to regulation at multiple levels including transcription, transcript processing, localization and ribonucleoside base modification. Post-transcriptional enzyme-catalyzed modification of tRNA occurs at a number of base and sugar positions and influences specific anticodon-codon interactions and regulates translation, its efficiency and fidelity...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28536422/secreted-frizzled-related-protein-4-sfrp4-chemo-sensitizes-cancer-stem-cells-derived-from-human-breast-prostate-and-ovary-tumor-cell-lines
#13
A Deshmukh, S Kumar, F Arfuso, P Newsholme, A Dharmarajan
This study investigated molecular signals essential to sustain cancer stem cells (CSCs) and assessed their activity in the presence of secreted frizzled-related protein 4 (sFRP4) alone or in combination with chemotherapeutic drugs. SFRP4 is a known Wnt antagonist, and is also pro-apoptotic and anti-angiogenic. Additionally, sFRP4 has been demonstrated to confer chemo-sensitization and improve chemotherapeutic efficacy. CSCs were isolated from breast, prostate, and ovary tumor cell lines, and characterized using tumor-specific markers such as CD44(+)/CD24(-)/CD133(+)...
May 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28536081/structural-annotation-of-beta-1-4-n-acetyl-galactosaminyltransferase-1-b4galnt1-causing-hereditary-spastic-paraplegia-26
#14
Rubina Dad, Uzma Malik, Aneela Javed, Berge A Minassian, Muhammad Jawad Hassan
Beta-1,4-N-acetyl galactosaminyltransferase 1, B4GALNT1, is a GM2/GD2 synthase, involved in the expression of glycosphingolipids (GSLs) containing sialic acid. Mutations in the gene B4GALNT1 cause Hereditary Spastic Paraplegia 26 (HSP26). In present study we have made attempt to predict the potential structural of the human B4GALNT1 protein. The results illustrated that the amino acid sequences of B4GALNT1 are not 100% conserved among selected twenty species. One signal peptide and one transmembrane domain predicted in human wild type B4GALNT1 protein with aliphatic index of 92...
May 20, 2017: Gene
https://www.readbyqxmd.com/read/28534506/lsd1-demethylates-hif1%C3%AE-to-inhibit-hydroxylation-and-ubiquitin-mediated-degradation-in-tumor-angiogenesis
#15
J-Y Lee, J-H Park, H-J Choi, H-Y Won, H-S Joo, D-H Shin, M K Park, B Han, K P Kim, T J Lee, C M Croce, G Kong
Lysine-specific demethylase 1 (LSD1), which has been considered as a potential therapeutic target in human cancer, has been known to regulate many biological functions through its non-histone substrates. Although LSD1-induced hypoxia-inducible factor alpha (HIF1α) demethylation has recently been proposed, the effect of LSD1 on the relationship between HIF1α post-translational modifications (PTMs) and HIF1α-induced tumor angiogenesis remains to be elucidated. Here, we identify a new methylation site of the HIF1α protein antagonized by LSD1 and the interplay between HIF1α protein methylation and other PTMs in regulating tumor angiogenesis...
May 22, 2017: Oncogene
https://www.readbyqxmd.com/read/28533144/discovery-of-two-p-superfamily-conotoxins-lt9a-and-lt9b-with-different-modifications-on-voltage-sensitive-sodium-channels
#16
Lei Wang, Junliang Liu, Zhenghua Ren, Yu Chen, Anlong Xu
In this work, two P-superfamily conotoxins, lt9a and lt9b, were purified and characterized from the crude venom of Conus litteratus. The amino acid sequences of lt9a and lt9b were determined by the Edman degradation method. It has been suggested that both lt9a and lt9b are produced from the precursor encoded by the gene Lt9.1. During the conotoxin maturation process, different post-translational modifications occurred between lt9a and lt9b. Conotoxin lt9b was predicted to have two prolines that underwent hydroxylation and one glutamate that underwent carboxylation, while lt9a had no hydroxyproline and carboxyglutamate residue...
May 19, 2017: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/28533032/design-and-synthesis-of-an-immobilized-metal-affinity-chromatography-and-metal-oxide-affinity-chromatography-hybrid-material-for-improved-phosphopeptide-enrichment
#17
Da-Song Yang, Xi-Ying Ding, Hong-Ping Min, Bo Li, Meng-Xiang Su, Miao-Miao Niu, Bin Di, Fang Yan
Reversible phosphorylation of proteins is one of the most important post-translational modifications, while the detection of phosphopeptides is difficult due to their low abundance and the signal suppression of nonphosphorylated peptides. Therefore, selective enrichment of phosphopeptides from highly complicated mixtures is vital for MS-based phosphoproteome analysis. Despite various strategies have been developed, there is no single method that is capable of providing full coverage of the whole phosphoproteome...
May 10, 2017: Journal of Chromatography. A
https://www.readbyqxmd.com/read/28533023/the-rna-modification-n-6-methyladenosine-and-its-implications-in-human-disease
#18
REVIEW
Pedro J Batista
Impaired gene regulation lies at the heart of many disorders, including developmental diseases and cancer. Furthermore, the molecular pathways that control gene expression are often the target of cellular parasites, such as viruses. Gene expression is controlled through multiple mechanisms that are coordinated to ensure the proper and timely expression of each gene. Many of these mechanisms target the life cycle of the RNA molecule, from transcription to translation. Recently, another layer of regulation at the RNA level involving RNA modifications has gained renewed interest of the scientific community...
May 19, 2017: Genomics, Proteomics & Bioinformatics
https://www.readbyqxmd.com/read/28530711/a-combinatorial-screen-of-the-cloud-uncovers-a-synergy-targeting-the-androgen-receptor
#19
Marco P Licciardello, Anna Ringler, Patrick Markt, Freya Klepsch, Charles-Hugues Lardeau, Sara Sdelci, Erika Schirghuber, André C Müller, Michael Caldera, Anja Wagner, Rebecca Herzog, Thomas Penz, Michael Schuster, Bernd Boidol, Gerhard Dürnberger, Yasin Folkvaljon, Pär Stattin, Vladimir Ivanov, Jacques Colinge, Christoph Bock, Klaus Kratochwill, Jörg Menche, Keiryn L Bennett, Stefan Kubicek
Approved drugs are invaluable tools to study biochemical pathways, and further characterization of these compounds may lead to repurposing of single drugs or combinations. Here we describe a collection of 308 small molecules representing the diversity of structures and molecular targets of all FDA-approved chemical entities. The CeMM Library of Unique Drugs (CLOUD) covers prodrugs and active forms at pharmacologically relevant concentrations and is ideally suited for combinatorial studies. We screened pairwise combinations of CLOUD drugs for impairment of cancer cell viability and discovered a synergistic interaction between flutamide and phenprocoumon (PPC)...
May 22, 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28529622/ires-mediated-protein-translation-overcomes-suppression-by-the-p14arf-tumor-suppressor-protein
#20
Song Xi, Ming Zhao, Si Wang, Ling Ma, Shensen Wang, Xianling Cong, Ruth A Gjerset, Rebecca C Fitzgerald, Yinghui Huang
Internal ribosome entry sites (IRES elements) have attracted interest in cancer gene therapy because they can be used in the design of gene transfer vectors that provide bicistronic co-expression of two transgene products under the control of a single promoter. Unlike cellular translation of most mRNAs, a process that requires a post-translational 5' modification of the mRNA known as the cap structure, IRES-mediated translation is independent of the cap structure. The cellular conditions that may intervene to modulate IRES-mediated, cap-independent versus cap-dependent translation, however, remain poorly understood, although they could be critical to the choice of gene transfer vectors...
2017: Journal of Cancer
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