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Post translational modification

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https://www.readbyqxmd.com/read/27922612/the-intricate-dance-of-post-translational-modifications-in-the-rhythm-of-life
#1
REVIEW
Arisa Hirano, Ying-Hui Fu, Louis J Ptáček
Endogenous biological rhythms with approximately 24-h periodicity are generated by the circadian clock, in which clock genes coordinate with one another and form a transcriptional-translational negative feedback loop. The precision of the circadian clock is further regulated by multiple post-translational modifications (PTMs), including phosphorylation, ubiquitination, acetylation and SUMOylation. Here, we review current understanding of the regulatory mechanisms of the core clock proteins by PTMs in the mammalian circadian clock...
December 6, 2016: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/27922609/the-molecular-basis-of-metabolic-cycles-and-their-relationship-to-circadian-rhythms
#2
REVIEW
Jane Mellor
Metabolic cycles result from the partitioning of oxidative and reductive metabolism into rhythmic phases of gene expression and oscillating post-translational protein modifications. Relatively little is known about how these switches in gene expression are controlled, although recent studies have suggested that transcription itself may play a central role. This review explores the molecular basis of the metabolic and gene-expression oscillations in the yeast Saccharomyces cerevisiae, as well as how they relate to other biological time-keeping mechanisms, such as circadian rhythms...
December 6, 2016: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/27922015/cryoem-structure-of-the-methanospirillum-hungatei-archaellum-reveals-structural-features-distinct-from-the-bacterial-flagellum-and-type-iv-pili
#3
Nicole Poweleit, Peng Ge, Hong H Nguyen, Rachel R Ogorzalek Loo, Robert P Gunsalus, Z Hong Zhou
Archaea use flagella known as archaella-distinct both in protein composition and structure from bacterial flagella-to drive cell motility, but the structural basis of this function is unknown. Here, we report an atomic model of the archaella, based on the cryo electron microscopy (cryoEM) structure of the Methanospirillum hungatei archaellum at 3.4 Å resolution. Each archaellum contains ∼61,500 archaellin subunits organized into a curved helix with a diameter of 10 nm and average length of 10,000 nm...
December 5, 2016: Nature Microbiology
https://www.readbyqxmd.com/read/27922006/structural-basis-of-myelin-associated-glycoprotein-adhesion-and-signalling
#4
Matti F Pronker, Suzanne Lemstra, Joost Snijder, Albert J R Heck, Dominique M E Thies-Weesie, R Jeroen Pasterkamp, Bert J C Janssen
Myelin-associated glycoprotein (MAG) is a myelin-expressed cell-adhesion and bi-directional signalling molecule. MAG maintains the myelin-axon spacing by interacting with specific neuronal glycolipids (gangliosides), inhibits axon regeneration and controls myelin formation. The mechanisms underlying MAG adhesion and signalling are unresolved. We present crystal structures of the MAG full ectodomain, which reveal an extended conformation of five Ig domains and a homodimeric arrangement involving membrane-proximal domains Ig4 and Ig5...
December 6, 2016: Nature Communications
https://www.readbyqxmd.com/read/27920818/exposition-of-hepatitis-b-surface-antigen-hbsag-on-the-surface-of-hek293t-cell-and-evaluation-of-its-expression
#5
Mina Mirian, Razieh Taghizadeh, Hossein Khanahmad, Mansour Salehi, Ali Jahanian-Najafabadi, Hojjat Sadeghi-Aliabadi, Shirin Kouhpayeh
Hepatitis B virus (HBV) is considered as a global health concern and hepatitis B surface antigen (HBsAg) is the most immunogenic protein of HBV. The purpose of this study was to evaluate the expression of HBsAg on the cell surface of human embryonic kidney cell line (HEK293T). After transformation of expression vector pcDNA/HBsAg to E.coli TOP10F', plasmid was extracted and digested with BglII. Afterwards, the linearized vector was transfected to cells and treated with hygromycin B for 5 weeks to expand the resulted clonies...
October 2016: Research in Pharmaceutical Sciences
https://www.readbyqxmd.com/read/27920257/pkr-mediates-inflammatory-response-induced-by-hyperosmotic-stress
#6
Kenneth T Farabaugh, Mithu Majumder, Bo-Jhih Guan, Raul Jobava, Jing Wu, Dawid Krokowski, Xing-Huang Gao, Andrew Schuster, Michelle Longworth, Edward D Chan, Massimiliano Bianchi, Madhusudan Dey, Antonis E Koromilas, Parameswaran Ramakrishnan, Maria Hatzoglou
High extracellular osmolarity results in a switch from an adaptive to an inflammatory gene expression program. We show that hyperosmotic stress activates the protein kinase R (PKR) independently of its RNA binding domain. In turn, PKR stimulated nuclear accumulation of nuclear factor-κB (NF-κB) p65 species phosphorylated at serine-536, which was paralleled by the induction of a subset of inflammatory NF-κB p65- responsive genes including inducible nitric oxide synthase (iNOS), IL-6, and IL-1β. The PKR mediated-hyperinduction of iNOS decreased cell survival in mouse embryonic fibroblasts via mechanisms involving nitric oxide (NO) synthesis and post-translational modification of proteins...
December 5, 2016: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/27919787/modulation-of-post-translational-modifications-in-%C3%AE-catenin-and-lrp6-inhibits-wnt-signaling-pathway-in-pancreatic-cancer
#7
Bharti Garg, Bhuwan Giri, Kaustav Majumder, Vikas Dudeja, Sulagna Banerjee, Ashok Saluja
β-catenin/Wnt Signaling pathway is critically regulated in a normal cell by a number of post-translational modifications. In pancreatic cancer however, aberrant activation of this pathway plays a significant role in tumor progression and metastasis. Though a number of studies have focused on understanding Wnt Signaling pathway in pancreatic cancer, there has been no systematic study to evaluate molecules that may be affecting this pathway. In the current study, we used a diterepende triepoxide, triptolide, to inhibit post-translational modifications in Wnt pathway and evaluated how this compound may be affecting the intricate signaling that regulates cell proliferation in pancreatic cancer...
December 2, 2016: Cancer Letters
https://www.readbyqxmd.com/read/27918991/sample-preparation-of-serum-to-allow-capillary-electrophoresis-analysis-of-prostate-specific-antigen-isoforms
#8
Noemi Farina-Gomez, Silvia Barrabes, Jorge E Gomez-Lopez, Monica Gonzalez, Angel Puerta, Diana Navarro-Calderon, Eduardo Albers-Acosta, Carlos Olivier, Jose C Diez-Masa, Rosa Peracaula, Mercedes de Frutos
Prostate cancer is the second most frequently diagnosed cancer in men worldwide. Currently prostate specific antigen (PSA) serum concentration is the most used prostate cancer marker, but it only shows limited specificity. Because PSA glycosylation is altered by prostate cancer, detecting glycosylation changes could increase PSA specificity as a prostate cancer marker. Changes in PSA glycosylation can modify its electrophoretic- behavior and techniques such as capillary zone electrophoresis (CZE) and two-dimensional electrophoresis (2-DE) could be applied to detect changes in PSA glycosylation...
November 24, 2016: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/27916542/the-role-of-the-ubiquitin-proteasome-system-in-the-memory-process
#9
REVIEW
Philomena Z Y Lip, Marilene Demasi, Diego Bonatto
Quite intuitive is the notion that memory formation and consolidation is orchestrated by protein synthesis because of the synaptic plasticity necessary for those processes. Nevertheless, recent advances have begun accumulating evidences of a high requirement for protein degradation on the molecular mechanisms of the memory process in the mammalian brain. Because degradation determines protein half-life, degradation has been increasingly recognized as an important intracellular regulatory mechanism. The proteasome is the main player in the degradation of intracellular proteins...
December 1, 2016: Neurochemistry International
https://www.readbyqxmd.com/read/27916117/specific-mixing-facilitates-the-comparative-quantification-of-phosphorylation-sites-with-significant-dysregulations
#10
Jing Liu, Bo Xu, Zheyi Liu, Mingming Dong, Jiawei Mao, Ye Zhou, Jin Chen, Fangjun Wang, Hanfa Zou
Mass spectrometry (MS) based quantitative analyses of proteome and proteome post-translational modifications (PTMs) play more and more important roles in biological, pharmaceutical and clinical studies. However, it is still a big challenge to accurately quantify the proteins or proteins PTM sites with extreme relative abundances in comparative protein samples, such as the significantly dysregulated ones. Herein, a novel quantification strategy, Mixing at Specific Ratio (MaSR) before isotope labeling, had been developed to improve the quantification accuracy and coverage of extreme proteins and protein phosphorylation sites...
January 15, 2017: Analytica Chimica Acta
https://www.readbyqxmd.com/read/27915381/regulation-of-non-homologous-end-joining-via-post-translational-modifications-of-components-of-the-ligation-step
#11
REVIEW
Kristína Durdíková, Miroslav Chovanec
DNA double-strand breaks are the most serious type of DNA damage and non-homologous end joining (NHEJ) is an important pathway for their repair. In Saccharomyces cerevisiae, three complexes mediate the canonical NHEJ pathway, Ku (Ku70/Ku80), MRX (Mre11/Rad50/Xrs2) and DNA ligase IV (Dnl4/Lif1). Mammalian NHEJ is more complex, primarily as a consequence of the fact that more factors are involved in the process, and also because higher chromatin organization and more complex regulatory networks exist in mammals...
December 3, 2016: Current Genetics
https://www.readbyqxmd.com/read/27913667/molecular-basis-for-specificity-of-the-met1-linked-polyubiquitin-signal
#12
REVIEW
Paul R Elliott
The post-translational modification of proteins provides a rapid and versatile system for regulating all signalling pathways. Protein ubiquitination is one such type of post-translational modification involved in controlling numerous cellular processes. The unique ability of ubiquitin to form polyubiquitin chains creates a highly complex code responsible for different subsequent signalling outcomes. Specialised enzymes ('writers') generate the ubiquitin code, whereas other enzymes ('erasers') disassemble it...
December 15, 2016: Biochemical Society Transactions
https://www.readbyqxmd.com/read/27913584/nitro-fatty-acid-pharmacokinetics-in-the-adipose-tissue-compartment
#13
Marco Fazzari, Nicholas K H Khoo, Steven R Woodcock, Diane K Jorkasky, Lihua Li, Francisco J Schopfer, Bruce A Freeman
Electrophilic nitro-fatty acids (NO2-FAs) promote adaptive and anti-inflammatory cell signaling responses as a result of an electrophilic character that supports post-translational protein modifications. A unique pharmacokinetic profile is expected for NO2-FAs because of an ability to undergo reversible reactions including Michael additions with biological cysteine-containing proteins and esterification into complex lipids. Herein we report via quantitative whole-body autoradiography analysis of rats gavaged with radiolabeled 10-nitro-[14C]oleic acid, preferential accumulation in adipose tissue over two weeks...
December 2, 2016: Journal of Lipid Research
https://www.readbyqxmd.com/read/27913416/mutagenesis-of-nosm-leader-peptide-reveals-important-elements-in-nosiheptide-biosynthesis
#14
Liang Jin, Xuri Wu, Yanjiu Xue, Yue Jin, Shuzhen Wang, Yijun Chen
: Nosiheptide, a typical member of ribosomally synthesized and post-translationally modified peptides (RiPPs), exhibits potent activity against multi-drug resistant Gram-positive bacterial pathogens. The precursor peptide of nosiheptide (NosM) is comprised of a leader peptide with 37 amino acids and a core peptide containing 13 amino acids. To pinpoint essential elements in the leader peptide for nosithpetide biosynthesis, a collection of mutants with unique sequence features, including N- and C-terminal motifs, peptide length as well as specific sites in the leader peptide, was generated by mutagenesis in vivo The effects of various mutants on nosiheptide biosynthesis were evaluated...
December 2, 2016: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/27912097/lncpress1-is-a-p53-regulated-lncrna-that-safeguards-pluripotency-by-disrupting-sirt6-mediated-de-acetylation-of-histone-h3k56
#15
Abhinav K Jain, Yuanxin Xi, Ryan McCarthy, Kendra Allton, Kadir C Akdemir, Lalit R Patel, Bruce Aronow, Chunru Lin, Wei Li, Liuqing Yang, Michelle C Barton
Recent evidence suggests that lncRNAs play an integral regulatory role in numerous functions, including determination of cellular identity. We determined global expression (RNA-seq) and genome-wide profiles (ChIP-seq) of histone post-translational modifications and p53 binding in human embryonic stem cells (hESCs) undergoing differentiation to define a high-confidence set of 40 lncRNAs, which are p53 transcriptional targets. We focused on lncRNAs highly expressed in pluripotent hESCs and repressed by p53 during differentiation to identify lncPRESS1 as a p53-regulated transcript that maintains hESC pluripotency in concert with core pluripotency factors...
December 1, 2016: Molecular Cell
https://www.readbyqxmd.com/read/27911737/the-conservation-of-phosphate-binding-residues-among-pht1-transporters-suggests-that-distinct-transport-affinities-are-unlikely-to-result-from-differences-in-the-phosphate-binding-site
#16
REVIEW
S Antony Ceasar, Alison Baker, Stephen P Muench, S Ignacimuthu, Stephen A Baldwin
The plant PHosphate Transporter 1 (PHT1) family of membrane proteins belongs to the major facilitator super family and plays a major role in the acquisition of inorganic phosphate (Pi) from the soil and its transport within the plant. These transporters have been well characterized for expression patterns, localization, and in some cases affinity. Furthermore, the crystal structure of a high-affinity eukaryotic phosphate transporter from the fungus Piriformospora indica (PiPT) has revealed important information on the residues involved in Pi transport...
October 15, 2016: Biochemical Society Transactions
https://www.readbyqxmd.com/read/27911734/the-spatiotemporal-regulation-of-ras-signalling
#17
REVIEW
Ana Herrero, David Matallanas, Walter Kolch
Nearly 30% of human tumours harbour mutations in RAS family members. Post-translational modifications and the localisation of RAS within subcellular compartments affect RAS interactions with regulator, effector and scaffolding proteins. New insights into the control of spatiotemporal RAS signalling reveal that activation kinetics and subcellular compartmentalisation are tightly coupled to the generation of specific biological outcomes. Computational modelling can help utilising these insights for the identification of new targets and design of new therapeutic approaches...
October 15, 2016: Biochemical Society Transactions
https://www.readbyqxmd.com/read/27910954/mal-lys-prediction-of-lysine-malonylation-sites-in-proteins-integrated-sequence-based-features-with-mrmr-feature-selection
#18
Yan Xu, Ya-Xin Ding, Jun Ding, Ling-Yun Wu, Yu Xue
Lysine malonylation is an important post-translational modification (PTM) in proteins, and has been characterized to be associated with diseases. However, identifying malonyllysine sites still remains to be a great challenge due to the labor-intensive and time-consuming experiments. In view of this situation, the establishment of a useful computational method and the development of an efficient predictor are highly desired. In this study, a predictor Mal-Lys which incorporated residue sequence order information, position-specific amino acid propensity and physicochemical properties was proposed...
December 2, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27909224/sarcomeric-protein-modification-during-adrenergic-stress-enhances-cross-bridge-kinetics-and-cardiac-output
#19
Kenneth S Gresham, Ranganath Mamidi, Jiayang Li, Hyerin Kwak, Julian E Stelzer
Molecular adaptations to chronic neurohormonal stress, including sarcomeric protein cleavage and phosphorylation, provide a mechanism to increase ventricular contractility and enhance cardiac output, yet the link between sarcomeric protein modifications and changes in myocardial function remains unclear. To examine the effects of neurohormonal stress on post-translational modifications of sarcomeric proteins, mice were administered combined α- and β-adrenergic receptor agonists (isoproterenol and phenylephrine; IPE) for 14 days using implantable osmotic pumps...
December 1, 2016: Journal of Applied Physiology
https://www.readbyqxmd.com/read/27908351/pim1-kinase-overexpression-enhances-ckit-cardiac-stem-cell-cardiac-repair-following-myocardial-infarction-in-swine
#20
Shathiyah Kulandavelu, Vasileios Karantalis, Julia Fritsch, Konstantinos E Hatzistergos, Viky Y Loescher, Frederic McCall, Bo Wang, Luiza Bagno, Samuel Golpanian, Ariel Wolf, Justin Grenet, Adam Williams, Aaron Kupin, Aaron Rosenfeld, Sadia Mohsin, Mark A Sussman, Azorides Morales, Wayne Balkan, Joshua M Hare
BACKGROUND: Pim1 kinase plays an important role in cell division, survival, and commitment of precursor cells towards a myocardial lineage, and overexpression of Pim1 in ckit(+) cardiac stem cells (CSCs) enhances their cardioreparative properties. OBJECTIVES: The authors sought to validate the effect of Pim1-modified CSCs in a translationally relevant large animal preclinical model of myocardial infarction (MI). METHODS: Human cardiac stem cells (hCSCs, n = 10), hckit(+) CSCs overexpressing Pim1 (Pim1(+); n = 9), or placebo (n = 10) were delivered by intramyocardial injection to immunosuppressed Yorkshire swine (n = 29) 2 weeks after MI...
December 6, 2016: Journal of the American College of Cardiology
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