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    16224 results match your criteria Biochemical Society Transactions[Journal]

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    Omega-3 fatty acids and inflammatory processes: from molecules to man.
    Biochem Soc Trans 2017 Sep 12. Epub 2017 Sep 12.
    Human Development and Health Academic Unit, Faculty of Medicine, University of Southampton, IDS Building, MP887 Southampton General Hospital, Tremona Road, Southampton SO16 6YD, U.K.
    Inappropriate, excessive or uncontrolled inflammation contributes to a range of human diseases. Inflammation involves a multitude of cell types, chemical mediators and interactions. The present article will describe nutritional and metabolic aspects of omega-6 (n-6) and omega-3 (n-3) fatty acids and explain the roles of bioactive members of those fatty acid families in inflammatory processes. Read More

    Geometries of vasculature bifurcation can affect the level of trophic damage during formation of a brain ischemic lesion.
    Biochem Soc Trans 2017 Sep 12. Epub 2017 Sep 12.
    Institute of Cytochemistry and Molecular Pharmacology, 6-th Radial'naya str. 24-14, Moscow 115404, Russia
    Ischemic lesion is a common cause of various diseases in humans. Brain tissue is especially sensitive to this type of damage. A common reason for the appearance of an ischemic area is a stop in blood flow in some branch of the vasculature system. Read More

    Structure and function of Pif1 helicase.
    Biochem Soc Trans 2017 Sep 12. Epub 2017 Sep 12.
    Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, U.S.A.
    Pif1 family helicases have multiple roles in the maintenance of nuclear and mitochondrial DNA in eukaryotes. Saccharomyces cerevisiae Pif1 is involved in replication through barriers to replication, such as G-quadruplexes and protein blocks, and reduces genetic instability at these sites. Another Pif1 family helicase in S. Read More

    Regulation of the cell cycle and centrosome biology by deubiquitylases.
    Biochem Soc Trans 2017 Sep 12. Epub 2017 Sep 12.
    Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool L69 3BX, U.K.
    Post-translational modification of proteins by ubiquitylation is increasingly recognised as a highly complex code that contributes to the regulation of diverse cellular processes. In humans, a family of almost 100 deubiquitylase enzymes (DUBs) are assigned to six subfamilies and many of these DUBs can remove ubiquitin from proteins to reverse signals. Roles for individual DUBs have been delineated within specific cellular processes, including many that are dysregulated in diseases, particularly cancer. Read More

    Role of conformational change and K-path ligands in controlling cytochrome c oxidase activity.
    Biochem Soc Trans 2017 Aug 24. Epub 2017 Aug 24.
    Department of Biochemistry and Molecular Biology, Michigan State University, 603 Wilson Rd, East Lansing, MI 48824, U.S.A.
    Given the central role of cytochrome c oxidase (CcO) in health and disease, it is an increasingly important question as to how the activity and efficiency of this key enzyme are regulated to respond to a variety of metabolic states. The present paper summarizes evidence for two modes of regulation of activity: first, by redox-induced conformational changes involving the K-proton uptake path; and secondly, by ligand binding to a conserved site immediately adjacent to the entrance of the K-path that leads to the active site. Both these phenomena highlight the importance of the K-path in control of CcO. Read More

    Visualising pattern recognition receptor signalling.
    Biochem Soc Trans 2017 Aug 24. Epub 2017 Aug 24.
    Department of Veterinary Medicine, The University of Cambridge, Madingley Road, Cambridge CB3 0ES, U.K.
    Signalling by pattern recognition receptors (PRRs) is critical for protecting the host against pathogens. Disruption of these signalling pathways has been implicated in many diseases ranging from infection susceptibility to cancer and autoimmune disease. Understanding how PRRs signal is of critical importance due to their potential as therapeutic targets to ameliorate symptoms of inflammatory diseases. Read More

    Structure of the Holliday junction: applications beyond recombination.
    Biochem Soc Trans 2017 Aug 24. Epub 2017 Aug 24.
    Department of Biochemistry and Molecular Biology, Colorado State University, 1870 Campus Delivery, Fort Collins, CO 80523-1870, U.S.A.
    The Holliday junction (HJ) is an essential element in recombination and related mechanisms. The structure of this four-stranded DNA assembly, which is now well-defined alone and in complex with proteins, has led to its applications in areas well outside of molecular recombination, including nanotechnology and biophysics. This minireview explores some interesting recent research on the HJ, as it has been adapted to design regular two- or three-dimensional lattices for crystal engineering, and more complex systems through DNA origami. Read More

    Mitochondrial health maintenance in axons.
    Biochem Soc Trans 2017 Aug 4. Epub 2017 Aug 4.
    F.M. Kirby Center for Neurobiology, Children's Hospital Boston, Boston, MA 02115, U.S.A.
    Neurons are post-mitotic cells that must function throughout the life of an organism. The high energetic requirements and Ca(2+) spikes of synaptic transmission place a burden on neuronal mitochondria. The removal of older mitochondria and the replenishment of the functional mitochondrial pool in axons with freshly synthesized components are therefore important parts of neuronal maintenance. Read More

    Consequences of RNA oxidation on protein synthesis rate and fidelity: implications for the pathophysiology of neuropsychiatric disorders.
    Biochem Soc Trans 2017 Aug 4. Epub 2017 Aug 4.
    Department of Biology, College of Sciences, University of Texas at San Antonio, San Antonio, TX 78249, U.S.A.
    Unlike DNA, oxidative damage to RNA has received little attention presumably due to the assumed transient nature of RNA. However, RNAs including mRNA can persist for several hours to days in certain tissues and are demonstrated to sustain greater oxidative damage than DNA. Because neuronal cells in the brain are continuously exposed to reactive oxygen species due to a high oxygen consumption rate, it is not surprising that neuronal RNA oxidation is observed as a common feature at an early stage in a series of neurodegenerative disorders. Read More

    Deciphering the regulation of metabolism with dynamic optimization: an overview of recent advances.
    Biochem Soc Trans 2017 Jul 28. Epub 2017 Jul 28.
    Research Group Medical Systems Biology, Christian-Albrechts-Universität zu Kiel, Kiel, Germany.
    Understanding optimality principles shaping the evolution of regulatory networks controlling metabolism is crucial for deriving a holistic picture of how metabolism is integrated into key cellular processes such as growth, adaptation and pathogenicity. While in the past the focus of research in pathway regulation was mainly based on stationary states, more recently dynamic optimization has proved to be an ideal tool to decipher regulatory strategies for metabolic pathways in response to environmental cues. In this short review, we summarize recent advances in the elucidation of optimal regulatory strategies and identification of optimal control points in metabolic pathways. Read More

    Interaction of misfolded proteins and mitochondria in neurodegenerative disorders.
    Biochem Soc Trans 2017 Jul 21. Epub 2017 Jul 21.
    Institute of Cell Biophysics Russian Academy of Sciences, Pushchino 142290, Russia.
    The number of the people affected by neurodegenerative disorders is growing dramatically due to the ageing of population. The major neurodegenerative diseases share some common pathological features including the involvement of mitochondria in the mechanism of pathology and misfolding and the accumulation of abnormally aggregated proteins. Neurotoxicity of aggregated β-amyloid, tau, α-synuclein and huntingtin is linked to the effects of these proteins on mitochondria. Read More

    Identification of optimal strategies for state transition of complex biological networks.
    Biochem Soc Trans 2017 Jul 21. Epub 2017 Jul 21.
    Simulation and Optimal Processes Group, Institute of Automation and Systems Engineering, Ilmenau University of Technology, Ilmenau 98684, Germany
    Complex biological networks typically contain numerous parameters, and determining feasible strategies for state transition by parameter perturbation is not a trivial task. In the present study, based on dynamical and structural analyses of the biological network, we optimized strategies for controlling variables in a two-node gene regulatory network and a T-cell large granular lymphocyte signaling network associated with blood cancer by using an efficient dynamic optimization method. Optimization revealed the critical value for each decision variable to steer the system from an undesired state into a desired attractor. Read More

    Nutritional modulation of metabolic inflammation.
    Biochem Soc Trans 2017 Aug 14;45(4):979-985. Epub 2017 Jul 14.
    Nutrigenomics Research Group, Conway Institute of Biomedical and Biomolecular Research, and Institute of Food and Health, University College Dublin, Belfield, Dublin, Ireland
    Metabolic inflammation is a very topical area of research, wherein aberrations in metabolic and inflammatory pathways probably contribute to atherosclerosis, insulin resistance (IR) and type 2 diabetes. Metabolic insults arising from obesity promote inflammation, which in turn impedes insulin signalling and reverse cholesterol transport (RCT). Key cells in the process are metabolically activated macrophages, which up-regulate both pro- and anti-inflammatory pathways in response to lipid spillover from adipocytes. Read More

    Post-transcriptional control of gene expression following stress: the role of RNA-binding proteins.
    Biochem Soc Trans 2017 Aug 14;45(4):1007-1014. Epub 2017 Jul 14.
    Medical Research Council Toxicology Unit, Lancaster Rd, Leicester LE1 9HN, U.K.
    The ability of mammalian cells to modulate global protein synthesis in response to cellular stress is essential for cell survival. While control of protein synthesis is mediated by the regulation of eukaryotic initiation and elongation factors, RNA-binding proteins (RBPs) provide a crucial additional layer to post-transcriptional regulation. RBPs bind specific RNA through conserved RNA-binding domains and ensure that the information contained within the genome and transcribed in the form of RNA is exported to the cytoplasm, chemically modified, and translated prior to folding into a functional protein. Read More

    RNA search engines empower the bacterial intranet.
    Biochem Soc Trans 2017 Aug 14;45(4):987-997. Epub 2017 Jul 14.
    Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1GA, U.K.
    RNA acts not only as an information bearer in the biogenesis of proteins from genes, but also as a regulator that participates in the control of gene expression. In bacteria, small RNA molecules (sRNAs) play controlling roles in numerous processes and help to orchestrate complex regulatory networks. Such processes include cell growth and development, response to stress and metabolic change, transcription termination, cell-to-cell communication, and the launching of programmes for host invasion. Read More

    How tetraspanins shape endothelial and leukocyte nano-architecture during inflammation.
    Biochem Soc Trans 2017 Aug 14;45(4):999-1006. Epub 2017 Jul 14.
    nAnostic Institute, Centre for Nanotechnology, Heisenbergstrasse 11, 48149 Münster, Germany
    Tetraspanins are ubiquitous membrane proteins that induce local membrane curvature and hence co-ordinate cell-to-cell contacts. This review highlights their role in inflammation, which requires control of the nano-architecture of attachment sites between endothelial cells and leukocytes. The active role of endothelial cells in preparing for transmigration of leukocytes and determining the severity of an inflammation is often underscored. Read More

    P-Rex1 and P-Rex2 RacGEFs and cancer.
    Biochem Soc Trans 2017 Aug 14;45(4):963-977. Epub 2017 Jul 14.
    Cancer Program, Monash Biomedicine Discovery Institute, and Department of Biochemistry and Molecular Biology, Monash University, 23 Innovation Walk, Clayton, VIC 3800, Australia
    Phosphatidylinositol 3,4,5-trisphosphate-dependent Rac exchanger (P-Rex) proteins are RacGEFs that are synergistically activated by phosphatidylinositol 3,4,5-trisphosphate and Gβγ subunits of G-protein-coupled receptors. P-Rex1 and P-Rex2 share similar amino acid sequence homology, domain structure, and catalytic function. Recent evidence suggests that both P-Rex proteins may play oncogenic roles in human cancers. Read More

    Regulation of the trafficking and the function of the metalloprotease ADAM10 by tetraspanins.
    Biochem Soc Trans 2017 Aug 7;45(4):937-944. Epub 2017 Jul 7.
    Inserm, U935, F-94807 Villejuif, France
    By interacting directly with partner proteins and with one another, tetraspanins organize a network of interactions referred to as the tetraspanin web. ADAM10 (A Disintegrin And Metalloprotease 10), an essential membrane-anchored metalloprotease that cleaves off the ectodomain of a large variety of cell surface proteins including cytokines, adhesion molecules, the precursor of the β-amyloid peptide APP or Notch, has emerged as a major component of the tetraspanin web. Recent studies have shown that ADAM10 associates directly with all members (Tspan5, Tspan10, Tspan14, Tspan15, Tspan17 and Tspan33) of a subgroup of tetraspanins having eight cysteines in the large extracellular domain and referred to as TspanC8. Read More

    Resource allocation in living organisms.
    Biochem Soc Trans 2017 Aug 7;45(4):945-952. Epub 2017 Jul 7.
    MaIAGE, INRA, Université Paris-Saclay, Jouy-en-Josas 78350, France
    Quantitative prediction of resource allocation for living systems has been an intensive area of research in the field of biology. Resource allocation was initially investigated in higher organisms by using empirical mathematical models based on mass distribution. A challenge is now to go a step further by reconciling the cellular scale to the individual scale. Read More

    Lnc-ing inflammation to disease.
    Biochem Soc Trans 2017 Aug 7;45(4):953-962. Epub 2017 Jul 7.
    Division of Chemical Systems & Synthetic Biology, Institute for Infectious Disease & Molecular Medicine (IDM), Faculty of Health Sciences, Department of Integrative Biomedical Sciences, University of Cape Town, Cape Town 7925, South Africa
    Termed 'master gene regulators' long ncRNAs (lncRNAs) have emerged as the true vanguard of the 'noncoding revolution'. Functioning at a molecular level, in most if not all cellular processes, lncRNAs exert their effects systemically. Thus, it is not surprising that lncRNAs have emerged as important players in human pathophysiology. Read More

    The sweet tooth of the circadian clock.
    Biochem Soc Trans 2017 Aug 3;45(4):871-884. Epub 2017 Jul 3.
    Program in Integrative Cell Signaling and Neurobiology of Metabolism, Yale University School of Medicine, New Haven, CT, U.S.A.
    The endogenous circadian clock is a key regulator of daily metabolic processes. On the other hand, circadian clocks in a broad range of tissues can be tuned by extrinsic and intrinsic metabolic cues. The bidirectional interaction between circadian clocks and metabolism involves both transcriptional and post-translational mechanisms. Read More

    Design starch: stochastic modeling of starch granule biogenesis.
    Biochem Soc Trans 2017 Aug 3;45(4):885-893. Epub 2017 Jul 3.
    Institute of Quantitative and Theoretical Biology, Heinrich-Heine University, Düsseldorf 40225, Germany.
    Starch is the most widespread and abundant storage carbohydrate in plants and the main source of carbohydrate in the human diet. Owing to its remarkable properties and commercial applications, starch is still of growing interest. Its unique granular structure made of intercalated layers of amylopectin and amylose has been unraveled thanks to recent progress in microscopic imaging, but the origin of such periodicity is still under debate. Read More

    Exercise protects from cancer through regulation of immune function and inflammation.
    Biochem Soc Trans 2017 Aug 3;45(4):905-911. Epub 2017 Jul 3.
    Centre of Inflammation and Metabolism and Centre for Physical Activity Research, Rigshospitalet, Faculty of Health Science, University of Copenhagen, Rigshospitalet 7641, Blegdamsvej 9, DK-2100 Copenhagen, Denmark
    Exercise training has been extensively studied in cancer settings as part of prevention or rehabilitation strategies, yet emerging evidence suggests that exercise training can also directly affect tumor-specific outcomes. The underlying mechanisms for this exercise-dependent cancer protection are just starting to be elucidated. To this end, evasion of immune surveillance and tumor-associated inflammation are established as hallmarks of cancer, and exercise may target cancer incidence and progression through regulation of these mechanisms. Read More

    Targeting the hepatocyte growth factor/Met pathway in cancer.
    Biochem Soc Trans 2017 Aug 3;45(4):855-870. Epub 2017 Jul 3.
    Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, U.S.A.
    Hepatocyte growth factor (HGF)-induced activation of its cell surface receptor, the Met tyrosine kinase, drives mitogenesis, motogenesis and morphogenesis in a wide spectrum of target cell types and embryologic, developmental and homeostatic contexts. Typical paracrine HGF/Met signaling is regulated by HGF activation at target cell surfaces, HGF binding-induced receptor activation, internalization and degradation. Despite these controls, HGF/Met signaling contributes to oncogenesis, tumor angiogenesis and invasiveness, and tumor metastasis in many types of cancer, leading to the rapid growth of pathway-targeted anticancer drug development programs. Read More

    Functions of long non-coding RNAs in human disease and their conservation in Drosophila development.
    Biochem Soc Trans 2017 Aug 3;45(4):895-904. Epub 2017 Jul 3.
    Brighton and Sussex Medical School, Medical Research Building, University of Sussex, Falmer, Brighton BN1 9PS, U.K.
    Genomic analysis has found that the transcriptome in both humans and Drosophila melanogaster features large numbers of long non-coding RNA transcripts (lncRNAs). This recently discovered class of RNAs regulates gene expression in diverse ways and has been involved in a large variety of important biological functions. Importantly, an increasing number of lncRNAs have also been associated with a range of human diseases, including cancer. Read More

    Functional interfaces between TICAM-2/TRAM and TICAM-1/TRIF in TLR4 signaling.
    Biochem Soc Trans 2017 Aug 19;45(4):929-935. Epub 2017 Jun 19.
    Department of Microbiology and Immunology, Graduate School of Medicine, Hokkaido University, Sapporo 060-8638, Japan
    Toll-like receptor 4 (TLR4) recognizes lipopolysaccharide (LPS), produces pro-inflammatory cytokines and type I interferons, and associates with a trigger of endotoxin shock. TLR4 is interacted with a TIR domain-containing adaptor molecule-2 (TICAM-2)/TRAM [TRIF (TIR domain-containing adaptor-inducing interferon-β)-related adaptor molecule] via its Toll-interleukin-1 receptor homology (TIR) domain. TICAM-2 acts as a scaffold protein and activates TIR domain-containing adaptor molecule-1 (TICAM-1)/TRIF. Read More

    Targeting the Ras palmitoylation/depalmitoylation cycle in cancer.
    Biochem Soc Trans 2017 Aug 19;45(4):913-921. Epub 2017 Jun 19.
    Centre for Molecular Medicine and Therapeutics, Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada V5Z 4H4
    The Ras proteins are well-known drivers of many cancers and thus represent attractive targets for the development of anticancer therapeutics. Inhibitors that disrupt the association of the Ras proteins with membranes by blocking the addition of the farnesyl lipid moiety to the Ras C-terminus failed in clinical trials. Here, we explore the possibility of targeting a second lipid modification, S-acylation, commonly referred to as palmitoylation, as a strategy to disrupt the membrane interaction of specific Ras isoforms. Read More

    Structure and function of DHHC protein S-acyltransferases.
    Biochem Soc Trans 2017 Aug 19;45(4):923-928. Epub 2017 Jun 19.
    Department of Molecular Medicine, College of Veterinary Medicine, Cornell University, Ithaca, NY, U.S.A.
    It has been estimated that 10% of the human genome encodes proteins that are fatty acylated at cysteine residues. The vast majority of these proteins are modified by members of the DHHC protein family, which carry out their enzymatic function on the cytoplasmic face of cell membranes. The biomedical importance of DHHC proteins is underscored by their association with human disease; unique and essential roles for DHHC proteins have been uncovered using DHHC-deficient mouse models. Read More

    Role of ESCRT component HD-PTP/PTPN23 in cancer.
    Biochem Soc Trans 2017 Jun;45(3):845-854
    Department of Biochemistry, McGill University, Montréal, Québec, Canada H3G 1Y6
    Sustained cellular signalling originated from the receptors located at the plasma membrane is widely associated with cancer susceptibility. Endosomal sorting and degradation of the cell surface receptors is therefore crucial to preventing chronic downstream signalling and tumorigenesis. Since the Endosomal Sorting Complexes Required for Transport (ESCRT) controls these processes, ESCRT components were proposed to act as tumour suppressor genes. Read More

    Fundamental principles of vascular network topology.
    Biochem Soc Trans 2017 Jun;45(3):839-844
    Mathematical Modelling and Statistical Analysis, Institute of Cytochemistry and Molecular Pharmacology, Moscow, Russia.
    The vascular system is arguably the most important biological system in many organisms. Although the general principles of its architecture are simple, the growth of blood vessels occurs under extreme physical conditions. Optimization is an important aspect of the development of computational models of the vascular branching structures. Read More

    Let there be light: how to use photoswitchable cross-linker to reprogram proteins.
    Biochem Soc Trans 2017 Jun;45(3):831-837
    Experimental Molecular Biophysics, Department of Physics, Freie Universität Berlin, Berlin 14195, Germany
    Azobenzene is a photo-isomerizing molecule whose end-to-end distance changes upon external illumination. When combined with site-specific reactive groups, it can be used as molecular tweezers to remote-control the structure and function of protein targets. The present study gives a brief overview over the rational design strategies that use an azobenzene-based photoswitchable cross-linker to engineer ON/OFF switches into functional proteins or to reprogram proteins for novel functions. Read More

    Mitochondrial cytochrome c oxidase: catalysis, coupling and controversies.
    Biochem Soc Trans 2017 Jun;45(3):813-829
    Glynn Laboratory of Bioenergetics, Institute of Structural and Molecular Biology, University College London, Gower Street, London WC1E 6BT, U.K.
    Mitochondrial cytochrome c oxidase is a member of a diverse superfamily of haem-copper oxidases. Its mechanism of oxygen reduction is reviewed in terms of the cycle of catalytic intermediates and their likely chemical structures. This reaction cycle is coupled to the translocation of protons across the inner mitochondrial membrane in which it is located. Read More

    Long noncoding RNAs: lincs between human health and disease.
    Biochem Soc Trans 2017 Jun;45(3):805-812
    Cancer Science Institute of Singapore, Centre for Translational Medicine, National University of Singapore, Singapore 117599
    Long noncoding RNAs (lncRNAs) represent one of the largest classes of transcripts and are highly diverse in terms of characteristics and functions. Advances in high-throughput sequencing platforms have enabled the rapid discovery and identification of lncRNAs as key regulatory molecules involved in various cellular processes and their dysregulation in various human diseases. Here, we summarize the current knowledge of the functions and underlying mechanisms of lncRNA activity with a particular focus on cancer biology. Read More

    A standard-enabled workflow for synthetic biology.
    Biochem Soc Trans 2017 Jun;45(3):793-803
    Department of Electrical and Computer Engineering, University of Utah, 50 S. Central Campus Drive, Rm. 2110, Salt Lake City, UT 84112, U.S.A.
    A synthetic biology workflow is composed of data repositories that provide information about genetic parts, sequence-level design tools to compose these parts into circuits, visualization tools to depict these designs, genetic design tools to select parts to create systems, and modeling and simulation tools to evaluate alternative design choices. Data standards enable the ready exchange of information within such a workflow, allowing repositories and tools to be connected from a diversity of sources. The present paper describes one such workflow that utilizes, among others, the Synthetic Biology Open Language (SBOL) to describe genetic designs, the Systems Biology Markup Language to model these designs, and SBOL Visual to visualize these designs. Read More

    Cell-free synthetic biology for in vitro prototype engineering.
    Biochem Soc Trans 2017 Jun;45(3):785-791
    Department of Medicine, Centre for Synthetic Biology and Innovation, South Kensington Campus, London, U.K.
    Cell-free transcription-translation is an expanding field in synthetic biology as a rapid prototyping platform for blueprinting the design of synthetic biological devices. Exemplar efforts include translation of prototype designs into medical test kits for on-site identification of viruses (Zika and Ebola), while gene circuit cascades can be tested, debugged and re-designed within rapid turnover times. Coupled with mathematical modelling, this discipline lends itself towards the precision engineering of new synthetic life. Read More

    CSBB: synthetic biology research at Newcastle University.
    Biochem Soc Trans 2017 Jun;45(3):781-783
    Interdisciplinary Computing and Complex BioSystems (ICOS), School of Computing Science, Newcastle University, Newcastle upon Tyne NE1 7RU, U.K.
    The Centre for Synthetic Biology and the Bioeconomy (CSBB) brings together a far-reaching multidisciplinary community across all Newcastle University's faculties - Medical Sciences, Science, Agriculture and Engineering, and Humanities, Arts and Social Sciences. The CSBB focuses on many different areas of Synthetic Biology, including bioprocessing, computational design and in vivo computation, as well as improving understanding of basic molecular machinery. Such breadth is supported by major national and international research funding, a range of industrial partners in the North East of England and beyond, as well as a large number of doctoral and post-doctoral researchers. Read More

    APPL1 is a multifunctional endosomal signaling adaptor protein.
    Biochem Soc Trans 2017 Jun;45(3):771-779
    Department of Biological Sciences, Vanderbilt University, Nashville, TN 37235, U.S.A.
    Endosomal adaptor proteins are important regulators of signaling pathways underlying many biological processes. These adaptors can integrate signals from multiple pathways via localization to specific endosomal compartments, as well as through multiple protein-protein interactions. One such adaptor protein that has been implicated in regulating signaling pathways is the adaptor protein containing a pleckstrin homology (PH) domain, phosphotyrosine-binding (PTB) domain, and leucine zipper motif 1 (APPL1). Read More

    The more the merrier: high-throughput single-molecule techniques.
    Biochem Soc Trans 2017 Jun;45(3):759-769
    Centre for Medical and Medicinal Bioscience, Illawarra Health and Medical Research Institute and School of Chemistry, University of Wollongong, Wollongong, NSW, Australia
    The single-molecule approach seeks to understand molecular mechanisms by observing biomolecular processes at the level of individual molecules. These methods have led to a developing understanding that for many processes, a diversity of behaviours will be observed, representing a multitude of pathways. This realisation necessitates that an adequate number of observations are recorded to fully characterise this diversity. Read More

    Substrate selectivity in the zDHHC family of S-acyltransferases.
    Biochem Soc Trans 2017 Jun;45(3):751-758
    Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow G4 0RE, U.K.
    S-acylation is a reversible lipid modification occurring on cysteine residues mediated by a family of membrane-bound 'zDHHC' enzymes. S-acylation predominantly results in anchoring of soluble proteins to membrane compartments or in the trafficking of membrane proteins to different compartments. Recent work has shown that although S-acylation of some proteins may involve very weak interactions with zDHHC enzymes, a pool of zDHHC enzymes exhibit strong and specific interactions with substrates, thereby recruiting them for S-acylation. Read More

    Molecular interactions shaping the tetraspanin web.
    Biochem Soc Trans 2017 Jun;45(3):741-750
    Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, 6525GA Nijmegen, The Netherlands
    To facilitate the myriad of different (signaling) processes that take place at the plasma membrane, cells depend on a high degree of membrane protein organization. Important mediators of this organization are tetraspanin proteins. Tetraspanins interact laterally among themselves and with partner proteins to control the spatial organization of membrane proteins in large networks called the tetraspanin web. Read More

    Structural insights into the alternative oxidases: are all oxidases made equal?
    Biochem Soc Trans 2017 Jun;45(3):731-740
    Biochemistry and Biomedicine, School of Life Sciences, University of Sussex, Falmer, Brighton BN1 9QG, U.K.
    The alternative oxidases (AOXs) are ubiquinol-oxidoreductases that are members of the diiron carboxylate superfamily. They are not only ubiquitously distributed within the plant kingdom but also found in increasing numbers within the fungal, protist, animal and prokaryotic kingdoms. Although functions of AOXs are highly diverse in general, they tend to play key roles in thermogenesis, stress tolerance (through the management of radical oxygen species) and the maintenance of mitochondrial and cellular energy homeostasis. Read More

    Scissor sisters: regulation of ADAM10 by the TspanC8 tetraspanins.
    Biochem Soc Trans 2017 Jun;45(3):719-730
    School of Biosciences, College of Life and Environmental Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, U.K.
    A disintegrin and metalloprotease 10 (ADAM10) is a ubiquitously expressed transmembrane protein which is essential for embryonic development through activation of Notch proteins. ADAM10 regulates over 40 other transmembrane proteins and acts as a 'molecular scissor' by removing their extracellular regions. ADAM10 is also a receptor for α-toxin, a major virulence factor of Staphylococcus aureus Owing to the importance of its substrates, ADAM10 is a potential therapeutic target for cancer, neurodegenerative diseases such as Alzheimer's and prion diseases, bacterial infection and inflammatory diseases such as heart attack, stroke and asthma. Read More

    A moving target: structure and disorder in pursuit of Myc inhibitors.
    Biochem Soc Trans 2017 Jun;45(3):709-717
    Astbury Centre for Structural Molecular Biology, School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, U.K.
    The Myc proteins comprise a family of ubiquitous regulators of gene expression implicated in over half of all human cancers. They interact with a large number of other proteins, such as transcription factors, chromatin-modifying enzymes and kinases. Remarkably, few of these interactions have been characterized structurally. Read More

    TSPAN7, effector of actin nucleation required for dendritic cell-mediated transfer of HIV-1 to T cells.
    Biochem Soc Trans 2017 Jun;45(3):703-708
    Molecular Pathogenesis Program, The Kimmel Center for Biology and Medicine of the Skirball Institute, New York University School of Medicine, New York, NY, U.S.A.
    Dendritic cells (DCs) have essential roles in early detection of pathogens and activation of both innate and adaptive immune responses. Whereas human DCs are resistant to productive HIV-1 replication, they have a unique ability to take up virus and transmit it efficiently to T lymphocytes. By doing that, HIV-1 may evade, at least in part, the first line of defense of the immune system, exploiting DCs instead to facilitate rapid infection of a large pool of immune cells. Read More

    Functions of protein phosphatase-6 in NF-κB signaling and in lymphocytes.
    Biochem Soc Trans 2017 Jun;45(3):693-701
    Center for Cell Signaling, University of Virginia School of Medicine, Charlottesville, VA 22908, U.S.A.
    Protein phosphatase-6 (PP6) is a member of the PPP family of Ser/Thr phosphatases involved in intracellular signaling. PP6 is conserved among all eukaryotes, and genetics in model organisms indicates it has non-redundant functions relative to other PPP phosphatases. PP6 functions in association with conserved SAPS subunits and, in vertebrate species, forms heterotrimers with Ankrd subunits. Read More

    How RNA acts as a nuclease: some mechanistic comparisons in the nucleolytic ribozymes.
    Biochem Soc Trans 2017 Jun;45(3):683-691
    Cancer Research UK Nucleic Acid Structure Research Group, MSI/WTB Complex, The University of Dundee, Dow Street, Dundee DD1 5EH, U.K.
    Recent structural and mechanistic studies have shed considerable light on the catalytic mechanisms of nucleolytic ribozymes. The discovery of several new ribozymes in this class has now allowed comparisons to be made, and the beginnings of mechanistic groupings to emerge. Read More

    The secret life of kinases: insights into non-catalytic signalling functions from pseudokinases.
    Biochem Soc Trans 2017 Jun;45(3):665-681
    Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3052, Australia
    Over the past decade, our understanding of the mechanisms by which pseudokinases, which comprise ∼10% of the human and mouse kinomes, mediate signal transduction has advanced rapidly with increasing structural, biochemical, cellular and genetic studies. Pseudokinases are the catalytically defective counterparts of conventional, active protein kinases and have been attributed functions as protein interaction domains acting variously as allosteric modulators of conventional protein kinases and other enzymes, as regulators of protein trafficking or localisation, as hubs to nucleate assembly of signalling complexes, and as transmembrane effectors of such functions. Here, by categorising mammalian pseudokinases based on their known functions, we illustrate the mechanistic diversity among these proteins, which can be viewed as a window into understanding the non-catalytic functions that can be exerted by conventional protein kinases. Read More

    Metal coordination in kinases and pseudokinases.
    Biochem Soc Trans 2017 Jun;45(3):653-663
    Department of Biochemistry, University of Kassel, Kassel 34132, Germany
    Protein phosphorylation, mediated by protein kinases, is a key event in the regulation of eukaryotic signal transduction. The majority of eukaryotic protein kinases perform phosphoryl transfer, assisted by two divalent metal ions. About 10% of all human protein kinases are, however, thought to be catalytically inactive. Read More

    Learning to read and write in evolution: from static pseudoenzymes and pseudosignalers to dynamic gear shifters.
    Biochem Soc Trans 2017 Jun;45(3):635-652
    Synthetic Systems Biology and Nuclear Organization, Swammerdam Institute for Life Sciences, University of Amsterdam, Science Park 904, 1098 XH Amsterdam, The Netherlands
    We present a systems biology view on pseudoenzymes that acknowledges that genes are not selfish: the genome is. With network function as the selectable unit, there has been an evolutionary bonus for recombination of functions of and within proteins. Many proteins house a functionality by which they 'read' the cell's state, and one by which they 'write' and thereby change that state. Read More

    Growing functions of the ESCRT machinery in cell biology and viral replication.
    Biochem Soc Trans 2017 Jun;45(3):613-634
    Faculty of Life Sciences & Medicine, Department of Infectious Diseases, King's College London, London, U.K.
    The vast expansion in recent years of the cellular processes promoted by the endosomal sorting complex required for transport (ESCRT) machinery has reinforced its identity as a modular system that uses multiple adaptors to recruit the core membrane remodelling activity at different intracellular sites and facilitate membrane scission. Functional connections to processes such as the aurora B-dependent abscission checkpoint also highlight the importance of the spatiotemporal regulation of the ESCRT machinery. Here, we summarise the role of ESCRTs in viral budding, and what we have learned about the ESCRT pathway from studying this process. Read More

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