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https://www.readbyqxmd.com/read/29351963/the-exon-junction-complex-structural-insights-into-a-faithful-companion-of-mammalian-mrnps
#1
REVIEW
Jennifer V Gerbracht, Niels H Gehring
During splicing, the exon junction complex (EJC) is deposited upstream of exon-exon boundaries. The EJC and its peripheral bound proteins play an essential role in mediating mRNA export, translation and turnover. However, the exact sequence of EJC assembly and the involved factors during splicing remain elusive. Recently published structures of the human C* spliceosome clarified the position of the EJC at this phase of splicing and have given insight into previously unidentified interactions between the EJC and spliceosomal proteins...
January 19, 2018: Biochemical Society Transactions
https://www.readbyqxmd.com/read/29348497/rna-binding-proteins-control-gene-expression-and-cell-fate-in-the-immune-system
#2
REVIEW
Martin Turner, Manuel D Díaz-Muñoz
RNA-binding proteins (RBPs) are essential for the development and function of the immune system. They interact dynamically with RNA to control its biogenesis and turnover by transcription-dependent and transcription-independent mechanisms. In this Review, we discuss the molecular mechanisms by which RBPs allow gene expression changes to occur at different speeds and to varying degrees, and which RBPs regulate the diversity of the transcriptome and proteome. These proteins are nodes for integration of transcriptional and signaling networks and are intimately linked to intermediary metabolism...
January 18, 2018: Nature Immunology
https://www.readbyqxmd.com/read/29346771/rapid-turnover-of-cortical-ncam1-regulates-synaptic-reorganization-after-peripheral-nerve-injury
#3
Hyoung-Gon Ko, Jun-Hyeok Choi, Dong Ik Park, SukJae Joshua Kang, Chae-Seok Lim, Su-Eon Sim, Jaehoon Shim, Ji-Il Kim, Siyong Kim, Tae-Hyeok Choi, Sanghyun Ye, Jaehyun Lee, Pojeong Park, Somi Kim, Jeehaeh Do, Jihye Park, Md Ariful Islam, Hyun Jeong Kim, Christoph W Turck, Graham L Collingridge, Min Zhuo, Bong-Kiun Kaang
Peripheral nerve injury can induce pathological conditions that lead to persistent sensitized nociception. Although there is evidence that plastic changes in the cortex contribute to this process, the underlying molecular mechanisms are unclear. Here, we find that activation of the anterior cingulate cortex (ACC) induced by peripheral nerve injury increases the turnover of specific synaptic proteins in a persistent manner. We demonstrate that neural cell adhesion molecule 1 (NCAM1) is one of the molecules involved and show that it mediates spine reorganization and contributes to the behavioral sensitization...
January 16, 2018: Cell Reports
https://www.readbyqxmd.com/read/29344730/skeletal-dissemination-in-paget-s-disease-of-the-spine
#4
REVIEW
Tim Rolvien, Sebastian Butscheidt, Jozef Zustin, Michael Amling
PURPOSE: Paget's disease of bone (PDB) is a common skeletal disorder that is associated with locally increased bone turnover, skeletal deformity and pain. We report a case of skeletal dissemination in PDB of the spine. METHODS: Case report. RESULTS: A 46-year-old former professional athlete suffered from disseminated PDB throughout the spine and hips after various surgical interventions including spondylodesis, bone grafting and bone morphogenetic protein (rhBMP-2) administration...
January 17, 2018: European Spine Journal
https://www.readbyqxmd.com/read/29343728/oxidation-of-sqstm1-p62-mediates-the-link-between-redox-state-and-protein-homeostasis
#5
Bernadette Carroll, Elsje G Otten, Diego Manni, Rhoda Stefanatos, Fiona M Menzies, Graham R Smith, Diana Jurk, Niall Kenneth, Simon Wilkinson, Joao F Passos, Johannes Attems, Elizabeth A Veal, Elisa Teyssou, Danielle Seilhean, Stéphanie Millecamps, Eeva-Liisa Eskelinen, Agnieszka K Bronowska, David C Rubinsztein, Alberto Sanz, Viktor I Korolchuk
Cellular homoeostatic pathways such as macroautophagy (hereinafter autophagy) are regulated by basic mechanisms that are conserved throughout the eukaryotic kingdom. However, it remains poorly understood how these mechanisms further evolved in higher organisms. Here we describe a modification in the autophagy pathway in vertebrates, which promotes its activity in response to oxidative stress. We have identified two oxidation-sensitive cysteine residues in a prototypic autophagy receptor SQSTM1/p62, which allow activation of pro-survival autophagy in stress conditions...
January 17, 2018: Nature Communications
https://www.readbyqxmd.com/read/29343718/the-bacterial-type-iii-toxin-antitoxin-system-toxin-is-a-dynamic-protein-rna-complex-with-stability-dependent-antiviral-abortive-infection-activity
#6
Francesca L Short, Chidiebere Akusobi, William R Broadhurst, George P C Salmond
Bacteria have evolved numerous defense systems to protect themselves from viral (bacteriophage) infection. The ToxIN system of Pectobacterium atrosepticum is a Type III toxin-antitoxin complex and "altruistic suicide" anti-phage system, which kills phage-infected cells through the release of a ribonuclease toxin, ToxN. ToxN is counteracted by a co-transcribed antitoxic RNA pseudoknot, ToxI, which self-assembles with ToxN into an inactive 3 ToxI:3 ToxN complex in vitro. However it is not known whether this complex is predominant in vivo, or how the complex is disassembled following infection to trigger a lethal, "altruistic" response...
January 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29342083/regulation-of-mitochondrial-dynamics-by-proteolytic-processing-and-protein-turnover
#7
REVIEW
Sumaira Ali, Gavin P McStay
The mitochondrial network is a dynamic organization within eukaryotic cells that participates in a variety of essential cellular processes, such as adenosine triphosphate (ATP) synthesis, central metabolism, apoptosis and inflammation. The mitochondrial network is balanced between rates of fusion and fission that respond to pathophysiologic signals to coordinate appropriate mitochondrial processes. Mitochondrial fusion and fission are regulated by proteins that either reside in or translocate to the inner or outer mitochondrial membranes or are soluble in the inter-membrane space...
January 17, 2018: Antioxidants (Basel, Switzerland)
https://www.readbyqxmd.com/read/29339803/carbohydrates-protect-protein-against-abiotic-fragmentation-by-soil-minerals
#8
Patrick N Reardon, Eric D Walter, Carrie L Marean-Reardon, Chad W Lawrence, Markus Kleber, Nancy M Washton
The degradation and turnover of soil organic matter is an important part of global carbon cycling and of particular importance with respect to attempts to predict the response of ecosystems to global climate change. Thus, it is important to mechanistically understand the processes by which organic matter can be degraded in the soil environment, including contact with reactive or catalytic mineral surfaces. We have characterized the outcome of the interaction of two minerals, birnessite and kaolinite, with two disaccharides, cellobiose and trehalose...
January 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29339500/regulation-of-the-stability-of-rgf1-receptor-by-the-ubiquitin-specific-proteases-ubp12-ubp13-is-critical-for-root-meristem-maintenance
#9
Zhichao An, Yuliang Liu, Yang Ou, Jia Li, Baowen Zhang, Daye Sun, Yu Sun, Wenqiang Tang
ROOT MERISTEM GROWTH FACTOR (RGF) 1 is an important peptide hormone that regulates root growth. Upon binding to its receptor, RGFR1, RGF1 regulates the expression of two transcription factors, PLETHORA 1 and 2 (PLT1/2), to influence root meristem development. Here, we show that the ubiquitin-specific proteases UBP12 and UBP13 are positive regulators of root meristem development and that UBP13 interacts directly with RGF1 receptor (RGFR1) and its close homolog RGFR2. The ubp12,13 double-mutant root is completely insensitive to exogenous applied RGF1...
January 16, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29338716/donor-age-affects-proteome-composition-of-tenocyte-derived-engineered-tendon
#10
Agnieszka J Turlo, Yalda Ashraf Kharaz, Peter D Clegg, James Anderson, Mandy J Peffers
BACKGROUND: The concept of tissue engineering is to deliver to the injury site biological scaffolds carrying functional cells that will enhance healing response. The preferred cell source is autologous in order to reduce immune response in the treated individual. However, in elderly patients age-related changes in synthetic activity of the implanted cells and subsequent alterations in tissue protein content may affect therapeutic outcomes. In this study we investigated the effect of donor age on proteome composition of tenocyte-derived tendon tissue-engineered constructs...
January 16, 2018: BMC Biotechnology
https://www.readbyqxmd.com/read/29338044/probing-the-changes-in-gene-expression-due-to-%C3%AE-crystallin-mutations-in-mouse-models-of-hereditary-human-cataract
#11
Usha P Andley, Eric Tycksen, Brittney N McGlasson-Naumann, Paul D Hamilton
The mammalian eye lens expresses a high concentration of crystallins (α, β and γ-crystallins) to maintain the refractive index essential for lens transparency. Crystallins are long-lived proteins that do not turnover throughout life. The structural destabilization of crystallins by UV exposure, glycation, oxidative stress and mutations in crystallin genes leads to protein aggregation and development of cataracts. Several destabilizing mutations in crystallin genes are linked with human autosomal dominant hereditary cataracts...
2018: PloS One
https://www.readbyqxmd.com/read/29337989/differentially-dimensioned-furrow-formation-by-zygotic-gene-expression-and-the-mbt
#12
Yi Xie, J Todd Blankenship
Despite extensive work on the mechanisms that generate plasma membrane furrows, understanding how cells are able to dynamically regulate furrow dimensions is an unresolved question. Here, we present an in-depth characterization of furrow behaviors and their regulation in vivo during early Drosophila morphogenesis. We show that the deepening in furrow dimensions with successive nuclear cycles is largely due to the introduction of a new, rapid ingression phase (Ingression II). Blocking the midblastula transition (MBT) by suppressing zygotic transcription through pharmacological or genetic means causes the absence of Ingression II, and consequently reduces furrow dimensions...
January 16, 2018: PLoS Genetics
https://www.readbyqxmd.com/read/29335437/deubiquitinase-usp13-dictates-mcl1-stability-and-sensitivity-to-bh3-mimetic-inhibitors
#13
Shengzhe Zhang, Meiying Zhang, Ying Jing, Xia Yin, Pengfei Ma, Zhenfeng Zhang, Xiaojie Wang, Wen Di, Guanglei Zhuang
MCL1 is a pivot member of the anti-apoptotic BCL-2 family proteins. While a distinctive feature of MCL1 resides in its efficient ubiquitination and destruction, the deubiquitinase USP9X has been implicated in the preservation of MCL1 expression by removing the polyubiquitin chains. Here we perform an unbiased siRNA screen and identify that the second deubiquitinase, USP13, regulates MCL1 stability in lung and ovarian cancer cells. Mechanistically, USP13 interacts with and stabilizes MCL1 via deubiquitination...
January 15, 2018: Nature Communications
https://www.readbyqxmd.com/read/29331378/loss-of-zebrafish-smyd1a-interferes-with-myofibrillar-integrity-without-triggering-the-misfolded-myosin-response
#14
Christoph Paone, Steven Rudeck, Christelle Etard, Uwe Strähle, Wolfgang Rottbauer, Steffen Just
Sarcomeric protein turnover needs to be tightly balanced to assure proper assembly and renewal of sarcomeric units within muscle tissues. The mechanisms regulating these fundamental processes are only poorly understood, but of great clinical importance since many cardiac and skeletal muscle diseases are associated with defective sarcomeric organization. The SET- and MYND domain containing protein 1b (Smyd1b) is known to play a crucial role in myofibrillogenesis by functionally interacting with the myosin chaperones Unc45b and Hsp90α1...
January 10, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29331050/exercise-counteracts-lipotoxicity-by-improving-lipid-turnover-and-lipid-droplet-quality
#15
Evelyn Zacharewicz, Matthijs K C Hesselink, Patrick Schrauwen
The incidence of obesity and metabolic disease, such as type 2 diabetes mellitus (T2D), are rising globally. Dietary lipid over-supply leads to lipid accumulation at ectopic sites, such as skeletal muscle. Ectopic lipid storage is highly correlated with insulin resistance and T2D, likely due to a loss of metabolic flexibility - the capacity to switch between fat and glucose oxidation upon insulin stimulation - and cellular dysfunction because of lipotoxicity. However, muscle lipid levels are also elevated in endurance trained athletes, presenting a paradoxical phenotype of increased intramuscular lipids along with high insulin sensitivity - the "athletes' paradox"...
January 13, 2018: Journal of Internal Medicine
https://www.readbyqxmd.com/read/29330291/keap1-inhibits-metastatic-properties-of-nsclc-cells-by-stabilizing-architectures-of-f-actin-and-focal-adhesions
#16
Bo Wu, Shu Yang, Haimei Sun, Tingyi Sun, Fengqing Ji, Yurong Wang, Lie Xu, Deshan Zhou
Low expression of the tumor suppressor, Kelch-like ECH-associated protein 1 (KEAP1) in non-small cell lung cancer (NSCLC) often results in higher malignant biological behavior and poor prognosis; however, the underlying mechanism remains unclear. The present study demonstrates that overexpression of Keap1 significantly suppresses migration and invasion of three different lung cancer cells (A549, H460, and H1299). Highly-expressed Keap1, compared to the control, promotes formation of multiple stress fibers with larger mature focal adhesion complexes in the cytoplasm where only fine focal adhesions were observed in the membrane under control conditions...
January 12, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29330095/crosstalk-between-rac1-mediated-actin-regulation-and-ros-production
#17
REVIEW
Alejandro Acevedo, Christian González-Billault
The small RhoGTPase Rac1 is implicated in a variety of events related to actin cytoskeleton rearrangement. Remarkably, another event that is completely different from those related to actin regulation has the same relevance; the Rac1-mediated production of reactive oxygen species (ROS) through NADPH oxidases (NOX). Each outcome involves different Rac1 downstream effectors; on one hand, events related to the actin cytoskeleton require Rac1 to bind to WAVEs proteins and PAKs that ultimately promote actin branching and turnover, on the other, NOX-derived ROS production demands active Rac1 to be bound to a cytosolic activator of NOX...
January 9, 2018: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/29326133/lipid-signaling-to-membrane-proteins-from-second-messengers-to-membrane-domains-and-adapter-free-endocytosis
#18
REVIEW
Donald W Hilgemann, Gucan Dai, Anthony Collins, Vincenzo Lariccia, Simona Magi, Christine Deisl, Michael Fine
Lipids influence powerfully the function of ion channels and transporters in two well-documented ways. A few lipids act as bona fide second messengers by binding to specific sites that control channel and transporter gating. Other lipids act nonspecifically by modifying the physical environment of channels and transporters, in particular the protein-membrane interface. In this short review, we first consider lipid signaling from this traditional viewpoint, highlighting innumerable Journal of General Physiology publications that have contributed to our present understanding...
January 11, 2018: Journal of General Physiology
https://www.readbyqxmd.com/read/29326099/interleukin-18-diagnostically-distinguishes-and-pathogenically-promotes-human-and-murine-macrophage-activation-syndrome
#19
Eric S Weiss, Charlotte Girard-Guyonvarc'h, Dirk Holzinger, Adriana A de Jesus, Zeshan Tariq, Jennifer Picarsic, Eduardo J Schiffrin, Dirk Foell, Alexei A Grom, Sandra Ammann, Stephan Ehl, Tomoaki Hoshino, Raphaela Goldbach-Mansky, Cem Gabay, Scott W Canna
Hemophagocytic Lymphohistiocytosis (HLH) and Macrophage Activation Syndrome (MAS) are life-threatening hyperferritinemic systemic inflammatory disorders. Though profound cytotoxic impairment causes familial HLH (fHLH), the mechanisms driving non-fHLH and MAS are largely unknown. MAS occurs in patients with suspected rheumatic disease, but the mechanistic basis for its distinction is unclear. Recently, a syndrome of recurrent MAS with infantile enterocolitis caused by NLRC4 inflammasome hyperactivity highlighted the potential importance of Interleukin (IL)-18...
January 11, 2018: Blood
https://www.readbyqxmd.com/read/29325746/first-report-of-the-characterization-of-a-snake-venom-apyrase-ruviapyrase-from-indian-russell-s-viper-daboia-russelii-venom
#20
Bhargab Kalita, Aparup Patra, Shagufta Jahan, Ashis K Mukherjee
A novel apyrase from Russell's viper venom (RVV) was purified and characterized, and it was named Ruviapyrase (Russell's viper apyrase). It is a high molecular weight (79.4 kDa) monomeric glycoprotein that contains 2.4% neutral sugars and 58.4% N-linked oligosaccharides and strongly binds to Concanavalin A. The LC-MS/MS analysis did not identify any protein in NCBI protein database, nevertheless some de novo sequences of Ruviapyrase showed putative conserved domain of apyrase superfamily. Ruviapyrase hydrolysed adenosine triphosphate (ATP) to a significantly greater extent (p < ...
January 8, 2018: International Journal of Biological Macromolecules
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