804 results match your criteria Biochemical Society symposium[Journal]


Trafficking of phosphatidylinositol by phosphatidylinositol transfer proteins.

Biochem Soc Symp 2007 (74):259-71

Lipid Signalling Group, Department of Physiology, University College London, London WC1E 6JJ UK.

PtdIns is synthesized at the endoplasmic reticulum and its intracellular distribution to other organelles can be facilitated by lipid transfer proteins [PITPs (phosphatidylinositol transfer proteins)]. In this review, I summarize the current understanding of how PITPs are regulated by phosphorylation, how can they dock to membranes to exchange their lipid cargo and how cells use PITPs in signal transduction and membrane delivery. Mammalian PITPs, PITPalpha and PITPbeta, are paralogous genes that are 94% similar in sequence. Read More

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http://dx.doi.org/10.1042/BSS0740259DOI Listing
July 2007
3 Reads

Regulation of phospholipase D activity, membrane targeting and intracellular trafficking by phosphoinositides.

Authors:
Andrew J Morris

Biochem Soc Symp 2007 (74):247-57

Department of Medicine, The Gill Heart Institute, University of Kentucky, 900 South Limestone Street, 326 Charles T. Wethington Building, Lexington, Kentucky 40536-0200, USA.

Generation of PA (phosphatidic acid) by PLD (phospholipase D)-catalysed hydrolysis of phosphatidylcholine plays a pivotal role in cellular signalling pathways that regulate organization of the actin cytoskeleton, vesicular transport and exocytosis and stimulation of cell growth and survival. PLD regulation and function are intimately linked with phosphoinositide metabolism. Phosphatidyl 4-phosphate 5-kinase is stimulated by PA in vitro and this enzyme is the downstream effector of a significant subset of PLD signalling pathways. Read More

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http://dx.doi.org/10.1042/BSS0740247DOI Listing

Evolution of the diverse biological roles of inositols.

Authors:
Robert H Michell

Biochem Soc Symp 2007 (74):223-46

School of Biosciences, University of Birmingham, Birmingham B15 2TT, UK.

Several of the nine hexahydroxycylohexanes (inositols) have functions in Biology, with myo-inositol (Ins) in most of the starring roles; and Ins polyphosphates are amongst the most abundant organic phosphate constituents on Earth. Many Archaea make Ins and use it as a component of diphytanyl membrane phospholipids and the thermoprotective solute di-L-Ins-1,1'-phosphate. Few bacteria make Ins or use it, other than as a carbon source. Read More

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http://dx.doi.org/10.1042/BSS0740223DOI Listing

Understanding the biological significance of diphosphoinositol polyphosphates ('inositol pyrophosphates').

Authors:
Stephen B Shears

Biochem Soc Symp 2007 (74):211-21

Inositide Signaling Group, National Institute of Environmental Health Sciences, NIH, DHHS, Research Triangle Park, PO Box 12233, NC 27709, USA.

Among the many derivatives of the inositol-based signalling family are a subgroup that possess diphosphates. In this review, some recent research into the actions of these specialized polyphosphates is analysed, and key goals for future studies are identified, which, it is hoped, will result in the wider cell-signalling community giving considerably greater attention to this intriguing but relatively neglected class of inositol polyphosphates. Read More

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http://dx.doi.org/10.1042/BSS0740211DOI Listing

Multiple functions of inositolphosphorylceramides in the formation and intracellular transport of glycosylphosphatidylinositol-anchored proteins in yeast.

Biochem Soc Symp 2007 (74):199-209

Department of Medicine and Biochemistry, University of Fribourg, Switzerland.

The mature sphingolipids of yeast consist of IPCs (inositolphosphorylceramides) and glycosylated derivatives thereof. Beyond being an abundant membrane constituent in the organelles of the secretory pathway, IPCs are also used to constitute the lipid moiety of the majority of GPI (glycosylphosphatidylinositol) proteins, while a minority of GPI proteins contain PI (phosphatidylinositol). Thus all GPI anchor lipids (as well as free IPCs) typically contain C26 fatty acids. Read More

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http://dx.doi.org/10.1042/BSS0740199DOI Listing
July 2007
2 Reads

Inositol polyphosphate kinases: regulators of nuclear function.

Biochem Soc Symp 2007 (74):183-97

Department of Pharmacology and Cancer Biology, Howard Hughes Medical Institute, Duke University Medical Center, DUMC 3813, Durham NC 27710, USA.

Recent work has uncovered roles for inositide signalling pathways downstream of phospholipase C activation and inositol 1,4,5-trisphosphate in the regulation of nuclear processes including gene expression, mRNA export and DNA metabolism. The identification of several IPKs (inositol polyphosphate kinases) has renewed interest in the cellular roles of inositol tetra-, penta-, hexa- and pyro-phosphates. Discoveries of inositide receptors and novel mechanisms of inositide action have provided important insights into how such messengers couple to nuclear machinery. Read More

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http://dx.doi.org/10.1042/BSS0740183DOI Listing
July 2007
1 Read

The inositol polyphosphate 5-phosphatases: traffic controllers, waistline watchers and tumour suppressors?

Biochem Soc Symp 2007 (74):161-81

Department of Biochemistry and Molecular Biology Monash University, Clayton, Victoria, Australia, 3800.

Phosphoinositide signals regulate cell proliferation, differentiation, cytoskeletal rearrangement and intracellular trafficking. Hydrolysis of PtdIns(4,5)P2 and PtdIns(3,4,5)P3, by inositol polyphosphate 5-phosphatases regulates synaptic vesicle recycling (synaptojanin-1), hematopoietic cell function [SHIP1(SH2-containing inositol polyphosphate 5-phosphatase-1)], renal cell function [OCRL (oculocerebrorenal syndrome of Lowe)] and insulin signalling (SHIP2). We present here a detailed review of the characteristics of the ten mammalian 5-phosphatases. Read More

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http://dx.doi.org/10.1042/BSS0740161DOI Listing

Type II PtdInsP kinases: location, regulation and function.

Biochem Soc Symp 2007 (74):149-59

Department of Pharmacology, Tennis Court Road, Cambridge CB2 1PD, UK.

The regulation of the synthesis of PtdIns(4,5)P2 is emerging as being as complex as we might expect from the multi-functional nature of this lipid. In the present chapter we focus on one aspect of inositide metabolism, which is the functions of the Type II PIPkins (Type II PtdInsP kinases). These are primarily PtdIns5P 4-kinases, although in vitro they will also phosphorylate PtdIns3P to PtdIns(3,4)P2. Read More

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http://dx.doi.org/10.1042/BSS0740149DOI Listing
July 2007
9 Reads

Phosphoinositides in phagolysosome and autophagosome biogenesis.

Biochem Soc Symp 2007 (74):141-8

Department of Molecular Genetics, University of New Mexico Health Sciences Center, 915 Camino de Salud, NE Albuquerque, NM 87131-001, USA.

Interconversions of phosphoinositides play a pivotal role during phagocytosis and at the subsequent stages of phagosomal maturation into the phagolysosome. Several model systems have been used to study the role of phosphoinositides in phagosomal membrane remodelling. These include phagosomes formed by inanimate objects such as latex beads, or pathogenic bacteria, e. Read More

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http://dx.doi.org/10.1042/BSS0740141DOI Listing
July 2007
3 Reads

Our FABulous VACation: a decade of phosphatidylinositol 3,5-bisphosphate.

Biochem Soc Symp 2007 (74):129-39

School of Biosciences, University of Birmingham, Birmingham B15 2TT, UK.

PtdIns(3,5)P2 was discovered about a decade ago and much of the machinery that makes, degrades and senses it has been uncovered. Despite this, we still lack a complete understanding of how the pieces fit together but some patterns are beginning to emerge. Molecular functions for PtdIns(3,5)P2 are also elusive, but the identification of effectors offers a way into some of these processes. Read More

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http://symposia.biochemistry.org/content/ppbioss/74/129.full
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http://symposia.biochemistry.org/bssymp/074/bss0740129.htm
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http://dx.doi.org/10.1042/BSS0740129DOI Listing

PtdIns5P: a little phosphoinositide with big functions?

Biochem Soc Symp 2007 (74):117-28

Inserm Unité 563, CPTP, Département d'Oncogenèse et Signalisation dans les Cellules Hématopoïétiques, IFR30, Hôpital Purpan, BP 3028 31024 Toulouse, France.

Phosphoinositides are minor constituents of cell membranes playing a critical role in the regulation of many cellular functions. Recent discoveries indicate that mutations in several phosphoinositide kinases and phosphatases generate imbalances in the levels of phosphoinositides, thereby leading to the development of human diseases. Although the roles of phosphoinositide 3-kinase products and PtdIns(4,5)P2 were largely studied these last years, the potential role of phosphatidylinositol monophosphates as direct signalling molecules is just emerging. Read More

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http://dx.doi.org/10.1042/BSS0740117DOI Listing
July 2007
24 Reads

The role of the phosphoinositides at the Golgi complex.

Biochem Soc Symp 2007 (74):107-16

Department of Cell Biology and Oncology, Consorzio Mario Negri Sud, Via Nazionale 8/A, 66030 Santa Maria Imbaro, Chieti, Italy.

Eukaryotic cells are organized into a complex system of subcompartments, each with its distinct protein and lipid composition. A continuous flux of membranes crosses these compartments, and in some cases direct connections exist between the different organelles. It is thus surprising that they can maintain their individual identities. Read More

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http://dx.doi.org/10.1042/BSS0740107DOI Listing
July 2007
2 Reads

Evolutionarily conserved structural and functional roles of the FYVE domain.

Biochem Soc Symp 2007 (74):95-105

Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.

The FYVE domain is an approx. 80 amino acid motif that binds to the phosphoinositide PtdIns3P with high specificity and affinity. It is present in 38 predicted gene products within the human genome, but only in 12-13 in Caenorhabditis elegans and Drosophila melanogaster. Read More

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http://symposia.biochemistry.org/bssymp/074/bss0740095.htm
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http://dx.doi.org/10.1042/BSS0740095DOI Listing
July 2007
3 Reads

Pleckstrin homology (PH) domains and phosphoinositides.

Authors:
Mark A Lemmon

Biochem Soc Symp 2007 (74):81-93

Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, 809C Stellar-Chance Laboratories, 422 Curie Boulevard, Philadelphia, PA 19104-6059, USA.

PH (pleckstrin homology) domains represent the 11th most common domain in the human proteome. They are best known for their ability to bind phosphoinositides with high affinity and specificity, although it is now clear that less than 10% of all PH domains share this property. Cases in which PH domains bind specific phosphoinositides with high affinity are restricted to those phosphoinositides that have a pair of adjacent phosphates in their inositol headgroup. Read More

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http://symposia.biochemistry.org/bssymp/074/bss0740081.htm
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http://dx.doi.org/10.1042/BSS0740081DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3777418PMC
July 2007
3 Reads

Substrate specificity and acute regulation of the tumour suppressor phosphatase, PTEN.

Biochem Soc Symp 2007 (74):69-80

Division of Molecular Physiology, Faculty of Life Sciences, Centre for Interdisciplinary Research, University of Dundee, Dundee DD1 5EH, UK.

PTEN (phosphatase and tensin homologue deleted on chromosome 10) is a tumour suppressor that functions as a PtdIns(3,4,5)P3 3-phosphatase to inhibit cell proliferation, survival and growth by antagonizing PI3K (phosphoinositide 3-kinase)-dependent signalling. Recent work has begun to focus attention on potential biological functions of the protein phosphatase activity of PTEN and on the possibility that some of its functions are phosphatase-independent. We discuss here the structural and regulatory mechanisms that account for the remarkable specificity of PTEN with respect to its PtdIns substrates and how it avoids the soluble headgroups of PtdIns that occur commonly in cells. Read More

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http://dx.doi.org/10.1042/BSS0740069DOI Listing
July 2007
2 Reads

The role of PI3Ks in the regulation of the neutrophil NADPH oxidase.

Biochem Soc Symp 2007 (74):59-67

The Babraham Institute, Babraham Research Campus, Cambridge CB2 4AT, UK.

The NADPH oxidase complex of neutrophils and macrophages is an important weapon used by these cells to kill microbial pathogens. The regulation of this enzyme complex is necessarily complicated by the diverse receptor types that are needed to trigger its activation and also the tight control that is required to deliver this activation at the appropriate time and place. As such, several signalling pathways have been established to regulate the NADPH oxidase downstream of cell surface receptors. Read More

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http://dx.doi.org/10.1042/BSS0740059DOI Listing
July 2007
2 Reads

Structural studies of phosphoinositide 3-kinase-dependent traffic to multivesicular bodies.

Biochem Soc Symp 2007 (74):47-57

MRC Laboratory of Molecular Biology, Medical Research Council Centre, Cambridge, CB2 2QH, UK.

Three large protein complexes known as ESCRT I, ESCRT II and ESCRT III drive the progression of ubiquitinated membrane cargo from early endosomes to lysosomes. Several steps in this process critically depend on PtdIns3P, the product of the class III phosphoinositide 3-kinase. Our work has provided insights into the architecture, membrane recruitment and functional interactions of the ESCRT machinery. Read More

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http://dx.doi.org/10.1042/BSS0740047DOI Listing
July 2007
33 Reads

Inositol lipids and TRPC channel activation.

Authors:
James W Putney

Biochem Soc Symp 2007 (74):37-45

National Institute of Environmental Health Sciences, NIH, Department of Health and Human Services, Research Triangle Park, NC 27709 USA.

The original hypothesis put forth by Bob Michell in his seminal 1975 review held that inositol lipid breakdown was involved in the activation of plasma membrane calcium channels or 'gates'. Subsequently, it was demonstrated that while the interposition of inositol lipid breakdown upstream of calcium signalling was correct, it was predominantly the release of Ca2+ that was activated, through the formation of Ins(1,4,5)P3. Ca2+ entry across the plasma membrane involved a secondary mechanism signalled in an unknown manner by depletion of intracellular Ca2+ stores. Read More

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http://dx.doi.org/10.1042/BSS0740037DOI Listing

PLCzeta, a sperm-specific PLC and its potential role in fertilization.

Biochem Soc Symp 2007 (74):23-36

Cell Signalling Laboratory, Wales Heart Research Institute, School of Medicine, Department of Obstetrics, Cardiff University, Cardiff CF14 4XN, UK.

A dramatic rise in intracellular calcium plays a vital role at the moment of fertilization, eliciting the resumption of meiosis and the initiation of embryo development. In mammals, the rise takes the form of oscillations in calcium concentration within the egg, driven by an elevation in inositol trisphosphate. The causative agent of these oscillations is proposed to be a recently described phosphoinositide-specific phospholipase C, PLCzeta, a soluble sperm protein that is delivered into the egg following membrane fusion. Read More

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http://dx.doi.org/10.1042/BSS0740023DOI Listing

The IP3 receptor/Ca2+ channel and its cellular function.

Biochem Soc Symp 2007 (74):9-22

Division of Molecular Neurobiology, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.

The IP3R [IP3 (inositol 1,4,5-trisphosphate) receptor] is responsible for Ca2+ release from the ER (endoplasmic reticulum). We have been working extensively on the P400 protein, which is deficient in Purkinje-neuron-degenerating mutant mice. We have discovered that P400 is an IP3R and we have determined the primary sequence. Read More

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http://dx.doi.org/10.1042/BSS0740009DOI Listing
July 2007
2 Reads

Inositol trisphosphate and calcium oscillations.

Biochem Soc Symp 2007 (74):1-7

The Babraham Institute, Babraham, Cambridge, CB2 4AT, UK.

InsP3 has two important functions in generating Ca2+ oscillations. It releases Ca2+ from the internal store and it can contribute to Ca2+ entry. A hypothesis has been developed to describe a mechanism for Ca2+ oscillations with particular emphasis on the way agonist concentration regulates oscillator frequency. Read More

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http://dx.doi.org/10.1042/BSS0740001DOI Listing

Core promoter-selective RNA polymerase II transcription.

Biochem Soc Symp 2006 (73):225-36

Transcription Laboratory, Marie Curie Research Institute, The Chart, Oxted, Surrey RH8 OTL, UK.

The initiation of mRNA synthesis in eukaryotic cells is a complex and highly regulated process that requires the assembly of general transcription factors and RNAP II (RNA polymerase II; also abbreviated as Pol II) into a pre-initiation complex at the core promoter. The core promoter is defined as the minimal DNA region that is sufficient to direct low levels of activator-independent (basal) transcription by RNAP II in vitro. The core promoter typically extends approx. Read More

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May 2006
6 Reads

Fluorescence resonance energy transfer as a method for dissecting in vivo mechanisms of transcriptional activation.

Biochem Soc Symp 2006 (73):217-24

Howard Hughes Medical Institute, Programs in Gene Function and Expression and Molecular Medicine, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA 01605, USA.

The first step in transcriptional activation of protein-coding genes involves the assembly on the promoter of a large PIC (pre-initiation complex) comprising RNA polymerase II and a suite of general transcription factors. Transcription is greatly enhanced by the action of promoter-specific activator proteins (activators) that function, at least in part, by increasing PIC formation. Activator-mediated stimulation of PIC assembly is thought to result from a direct interaction between the activator and one or more components of the transcription machinery, termed the 'target'. Read More

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The RNA polymerase I transcription machinery.

Biochem Soc Symp 2006 (73):203-16

Division of Gene Regulation and Expression, School of Life Sciences, University of Dundee, Wellcome Trust Biocentre, Dundee DD1 5EH, UK.

The rRNAs constitute the catalytic and structural components of the ribosome, the protein synthesis machinery of cells. The level of rRNA synthesis, mediated by Pol I (RNA polymerase I), therefore has a major impact on the life and destiny of a cell. In order to elucidate how cells achieve the stringent control of Pol I transcription, matching the supply of rRNA to demand under different cellular growth conditions, it is essential to understand the components and mechanics of the Pol I transcription machinery. Read More

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http://link.springer.com/content/pdf/10.1007%2F978-1-4614-05
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http://symposia.biochemistry.org/content/ppbioss/73/203.full
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3858827PMC
May 2006
4 Reads

The modulation of WTI transcription function by cofactors.

Biochem Soc Symp 2006 (73):191-201

Faculty of Life Sciences, The Michael Smith Building, University of Manchester, Oxford Road, Manchester M13 9PT, UK.

Wilms' tumour is a paediatric malignancy of the kidneys that affects one in every 10,000 live births, making it the most common solid tumour in the young. This cancer arises due to a failure of the metanephric mesenchyme to differentiate and form the kidney filtration units and tubules, which instead undergo uncontrolled proliferation. WT1 (Wilms' tumour 1) was identified as a factor that is frequently mutated in Wilms' tumours. Read More

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May 2006
1 Read

The p53 response during DNA damage: impact of transcriptional cofactors.

Biochem Soc Symp 2006 (73):181-9

Laboratory of Cancer Biology, Division of Medical Sciences, University of Oxford, Oxford OX3 9DU, UK.

Defects in the DNA damage response pathways can lead to tumour development. The tumour suppressor p53 is a key player in the DNA damage response, and the precise regulation of p53 is critical for the suppression of tumorigenesis. DNA damage induces the activity of p53, via damage sensors such as ATM (ataxia telangiectasia mutated) and ATR (ataxia telangiectasia-related), which leads to the transcriptional regulation of a variety of genes involved in cell cycle control and apoptosis. Read More

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May 2006
1 Read

Regulation of NF-kappaB function.

Biochem Soc Symp 2006 (73):165-80

School of Life Sciences, Division of Gene Regulation and Expression, MSI/WTB Complex, Dow Street, University of Dundee, Dundee DD1 5EH, Scotland, UK.

In the 20 years since its discovery, research into the NF-kappaB (nuclear factor-kappaB) family of transcription factors has revealed an amazing diversity of functions. NF-kappaB proteins are regulators of the immune, inflammatory, stress, proliferative and apoptotic responses of a cell to a very large number of different stimuli. NF-kappaB complexes can be found in all cell types, indicating that the number of different contexts in which NF-kappaB can become induced is enormous. Read More

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May 2006
3 Reads

Both normal and polyglutamine- expanded ataxin-7 are components of TFTC-type GCN5 histone acetyltransferase- containing complexes.

Biochem Soc Symp 2006 (73):155-63

Department of Molecular Pathology, Institut de Génétique et de Biologie Moléculaire et Cellulaire, UMR 7104, CNRS/IN SER M/ULP, BP 10142, 67404 Illkirch Cedex, France.

SCA7 (spinocerebellar ataxia type 7) is a neurodegenerative disorder caused by a CAG repeat expansion in the SCA7 gene that leads to elongation of a polyglutamine tract in ataxin-7, a protein of unknown function. Sgf73, a putative yeast orthologue of ataxin-7, has been identified as a new component of the yeast SAGA (Spt/Ada/Gcn5 acetyltransferase) multisubunit complex, a co-activator required for the transcription of a subset of RNA polymerase II-dependent genes. We show here that ataxin-7 is an integral component of mammalian SAGA-like complexes, i. Read More

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May 2006
5 Reads

Activation by c-Myc of transcription by RNA polymerases I, II and III.

Biochem Soc Symp 2006 (73):141-54

Institute of Biomedical and Life Sciences, Division of Biochemistry and Molecular Biology, University of Glasgow, Glasgow G12 8QQ, UK.

The proto-oncogene product c-Myc can induce cell growth and proliferation. It regulates a large number of RNA polymerase II-transcribed genes, many of which encode ribosomal proteins, translation factors and other components of the biosynthetic apparatus. We have found that c-Myc can also activate transcription by RNA polymerases I and III, thereby stimulating production of rRNA and tRNA. Read More

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May 2006
5 Reads
32 Citations

Non-coding RNA in transcription initiation.

Biochem Soc Symp 2006 (73):131-40

Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK.

Diverse classes of non-coding RNAs, including snRNAs (small nuclear RNAs), play fundamental regulatory roles in gene expression. For example, 7SK RNA and the components of the splicing apparatus U1-U6 snRNAs are implicated in the regulation of transcriptional elongation. The first evidence for the involvement of RNA in the regulation of transcriptional initiation is now emerging. Read More

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May 2006
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Convergence of the SUMO and MAPK pathways on the ETS-domain transcription factor Elk-1.

Biochem Soc Symp 2006 (73):121-9

Faculty of Life Sciences, University of Manchester, Michael Smith Building, Oxford Road, Manchester M13 9PT, UK.

The ETS-domain transcription factor Elk-1 is regulated by phosphorylation in response to activation of the MAPK (mitogen-activated protein kinase) pathways. This phosphorylation triggers a series of molecular events that convert Elk-1 from a transcriptionally silent state into a highly active state and then back to a basal level. At the same time, activation of the ERK (extracellular-signal-regulated kinase) MAPK pathway leads to loss of modification of Elk-1 by SUMO (small ubiquitin-related modifier). Read More

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May 2006
3 Reads

Nucleosome dynamics.

Biochem Soc Symp 2006 (73):109-19

Division of Gene Regulation and Expression, School of Life Sciences, University of Dundee, Dundee DDI 5EH, Scotland, UK.

In the 30 years since the discovery of the nucleosome, our picture of it has come into sharp focus. The recent high-resolution structures have provided a wealth of insight into the function of the nucleosome, but they are inherently static. Our current knowledge of how nucleosomes can be reconfigured dynamically is at a much earlier stage. Read More

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May 2006
5 Reads

Chromatin-remodelling factors and the maintenance of transcriptional states through DNA replication.

Biochem Soc Symp 2006 (73):97-108

Marie Curie Research Institute, The Chart, Oxted RH8 0TL, Surrey, UK.

At the replication fork, nucleosomes, transcription factors and RNA polymerases are stripped off the DNA, the DNA double strands are unzipped and DNA methylation marks may be erased. Therefore DNA replication is both a 'curse' and 'bliss' for the epigenome, as it disrupts its stability by causing chromatin perturbations, yet it offers an opportunity to initiate changes in chromatin architecture and gene expression patterns, especially during development. Thus the DNA replication site is a critical point for regulation. Read More

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Nutrient-regulated gene expression in eukaryotes.

Biochem Soc Symp 2006 (73):85-96

Faculty of Life Sciences, University of Manchester, The Michael Smith Building, Oxford Road, Manchester M13 9PT, UK.

The recognition of changes in environmental conditions, and the ability to adapt to these changes, is essential for the viability of cells. There are numerous well characterized systems by which the presence or absence of an individual metabolite may be recognized by a cell. However, the recognition of a metabolite is just one step in a process that often results in changes in the expression of whole sets of genes required to respond to that metabolite. Read More

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May 2006
5 Reads

A role for upstream binding factor in organizing ribosomal gene chromatin.

Biochem Soc Symp 2006 (73):77-84

Biomedical Research Centre, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, Scotland, UK.

Human ribosomal genes are located in NORs (nucleolar organizer regions) on the short arms of acrocentric chromosomes. During metaphase, previously active NORs appear as prominent chromosomal features termed secondary constrictions, which are achromatic in chromosome banding and positive in silver staining. The architectural RNA polymerase I transcription factor UBF (upstream binding factor) binds extensively across the ribosomal gene repeat throughout the cell cycle. Read More

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May 2006
3 Reads

Specialized transcription factories.

Biochem Soc Symp 2006 (73):67-75

Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK.

We have previously suggested a model for the eukaryotic genome based on the structure of the bacterial nucleoid where active RNA polymerases cluster to loop the intervening DNA. This organization of polymerases into clusters--which we call transcription 'factories'--has important consequences. For example, in the nucleus of a HeLa cell the concentration of soluble RNA polymerase II is approximately 1 mM, but the local concentration in a factory is 1000-fold higher. Read More

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May 2006
6 Reads

The relationship between higher-order chromatin structure and transcription.

Biochem Soc Symp 2006 (73):59-66

MRC Human Genetics Unit, Western General Hospital, Edinburgh EH4 2XU, UK.

It has generally been assumed that transcriptionally active genes are in an 'open' chromatin structure and that silent genes have a 'closed' chromatin structure. Here we re-assess this axiom in the light of genome-wide studies of chromatin fibre structure. Using a combination of sucrose gradient sedimentation and genomic microarrays of the human genome, we argue that open chromatin fibres originate from regions of high gene density, whether or not those genes are transcriptionally active. Read More

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May 2006
2 Reads

Modulation of RNA polymerase core functions by basal transcription factor TFB/TFIIB.

Biochem Soc Symp 2006 (73):49-58

Imperial College London, Division of Cell and Molecular Biology, Sir Alexander Fleming Building, Exhibition Road, London SW7 2AZ, UK.

The archaeal basal transcriptional machinery consists of TBP (TATA-binding protein), TFB (transcription factor B; a homologue of eukaryotic TFIIB) and an RNA polymerase that is structurally very similar to eukaryotic RNA polymerase II. This constellation of factors is sufficient to assemble specifically on a TATA box-containing promoter and to initiate transcription at a specific start site. We have used this system to study the functional interaction between basal transcription factors and RNA polymerase, with special emphasis on the post-recruitment function of TFB. Read More

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May 2006
2 Reads

Mechanistic studies of the mRNA transcription cycle.

Authors:
Patrick Cramer

Biochem Soc Symp 2006 (73):41-7

Gene Center, Ludwig-Maximilians-University of Munich, Department of Chemistry and Biochemistry, Feodor-Lynen-Str. 25, 81377 Munich, Germany.

We have now completed an atomic crystallographic model of the 12-subunit yeast RNA polymerase II in elongation mode, with DNA and RNA in the active-centre cleft, and the NTP substrate at the growing end of the RNA. From these studies has emerged a detailed three-dimensional view of mRNA elongation. We have extended this structural analysis to a polymerase elongation complex bound by the transcript cleavage factor TFIIS (transcription factor IIS), which is required for polymerase escape from DNA arrest sites. Read More

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May 2006
1 Read

MOZ fusion proteins in acute myeloid leukaemia.

Biochem Soc Symp 2006 (73):23-39

School of Pharmacy, University of Nottingham, University Park, Nottingham NG7 2RD, UK.

MOZ (monocytic leukaemia zinc finger protein; also known as ZNF220 or MYST3) is a member of the MYST family of protein acetyltransferases. Chromosomal translocations involving the MOZ gene are associated with AML (acute myeloid leukaemia), suggesting that it has a role in haematopoiesis. Recurrent reciprocal translocations fuse the MOZ gene [or the gene encoding MORF (MOZ-related factor); also known as MYST4] to genes encoding the nuclear receptor co-activators CBP [CREB (cAMP response element-binding protein)-binding protein], p300 or the p160 protein TIF2 (transcription intermediary factor 2). Read More

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May 2006
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How transcriptional and epigenetic programmes are played out on an individual mammalian gene cluster during lineage commitment and differentiation.

Biochem Soc Symp 2006 (73):11-22

MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford OX3 9DS, UK.

In the post-genomic era, a great deal of work has focused on understanding how DNA sequence is used to programme complex nuclear, cellular and tissue functions throughout differentiation and development. There are many approaches to these issues, but we have concentrated on understanding how a single mammalian gene cluster is activated or silenced as stem cells undergo lineage commitment, differentiation and maturation. In particular we have analysed the alpha globin cluster, which is expressed in a cell-type- and developmental stage-specific manner in the haemopoietic system. Read More

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May 2006
5 Reads
3 Citations

Investigations of the modular structure of bacterial promoters.

Biochem Soc Symp 2006 (73):1-10

School of Biosciences, The University of Birmingham, Birmingham B15 2TT, UK.

Bacterial RNA polymerase holoenzyme carries different determinants that contact different promoter DNA sequence elements. These contacts are essential for the recognition of promoters prior to transcript initiation. Here, we have investigated how active promoters can be built from different combinations of elements. Read More

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Mitochondrial superoxide and aging: uncoupling-protein activity and superoxide production.

Biochem Soc Symp 2004 (71):203-13

MRC Dunn Human Nutrition Unit, Hills Road, Cambridge CB2 2XY, U.K.

Mitochondria are a major source of superoxide, formed by the one-electron reduction of oxygen during electron transport. Superoxide initiates oxidative damage to phospholipids, proteins and nucleic acids. This damage may be a major cause of degenerative disease and aging. Read More

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http://symposia.biochemistry.org/content/ppbioss/71/203.full
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April 2005
4 Reads

Metallic prions.

Authors:
David R Brown

Biochem Soc Symp 2004 (71):193-202

Department of Biology and Biochemistry, 4 South, University of Bath, Calverton Down, Bath BA2 7AY, U.K.

Prion diseases, also referred to as transmissible spongiform encephalopathies, are characterized by the deposition of an abnormal isoform of the prion protein in the brain. However, this aggregated, fibrillar, amyloid protein, termed PrPSc, is an altered conformer of a normal brain glycoprotein, PrPc. Understanding the nature of the normal cellular isoform of the prion protein is considered essential to understanding the conversion process that generates PrPSc. Read More

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April 2005
4 Reads

Generation of bile pigments by haem oxygenase: a refined cellular strategy in response to stressful insults.

Biochem Soc Symp 2004 (71):177-92

Vascular Biology Unit, Department of Surgical Research, Northwick Park Institute for Medical Research, Harrow, Middlesex HAI 3UJ, U.K.

The family of haem oxygenase enzymes is unique in nature for its role in haem degradation. Haem is cleaved at the alpha-meso position by haem oxygenase with the support of electrons donated by cytochrome P450 reductase, the first products of this reaction being CO, iron and biliverdin. Biliverdin is then converted to bilirubin by biliverdin reductase. Read More

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April 2005
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Antioxidant and cytoprotective responses to redox stress.

Biochem Soc Symp 2004 (71):157-76

Biomedical Research Centre, University of Dundee, Ninewells Hospital and Medical School, Dundee DD I 9SY, U.K.

Aerobic cells produce reactive oxygen species as a consequence of normal cellular metabolism, and an array of antioxidant systems are in place to maintain the redox balance. When the redox equilibrium of the cell is upset by pro-oxidant environmental stimuli, adaptive responses to the redox stress take place, which can result in up-regulation of antioxidant proteins and detoxification enzymes. Over the past few years, it has become apparent that members of the CNC (cap 'n' collar)-basic leucine zipper family of transcription factors are principal mediators of defensive responses to redox stress. Read More

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April 2005
2 Reads

Modulation of the L-arginine/nitric oxide signalling pathway in vascular endothelial cells.

Biochem Soc Symp 2004 (71):143-56

Centre for Cardiovascular Biology and Medicine, Guy's, King's and St. Thomas' School of Biomedical Sciences, New Hunt's House, King's College London, Guy's Campus, London SEI IUL, U.K.

Nitric oxide (NO) is synthesized from L-arginine, and in endothelial cells influx of L-arginine is mediated predominantly via Na+-independent cationic amino acid transporters. Constitutive, Ca2+-calmodulin-sensitive eNOS (endothelial nitric oxide synthase) metabolizes L-arginine to NO and L-citrulline. eNOS is present in membrane caveolae and the cytosol and requires tetrahydrobiopterin, NADPH, FAD and FMN as additional cofactors for its activity. Read More

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http://symposia.biochemistry.org/content/ppbioss/71/143.full
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April 2005
2 Reads

Regulation of vascular function by haemoglobin.

Biochem Soc Symp 2004 (71):135-42

Department of Pathology, Center for Free Radical Biology, University of Alabama at Birmingham, Biomedical Research Building II, 901 19th Street South, Birmingham, AL 35294, USA.

A critical element in the ability of endothelial NO to function in the vasculature is preventing its reaction with erythrocytic Hb (haemoglobin). Emerging concepts suggest that the biophysical and rheological properties of the red blood cell are important in meeting this criterion. It has been recognized for some time that cell-free Hb may react with endothelial NO and that this may underlie the problems with Hb-based blood substitutes. Read More

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Clinical aspects of reactive oxygen and nitrogen species.

Biochem Soc Symp 2004 (71):121-33

Universitätsklinikum Hamburg-Eppendorf, Medizinische Klinik III, Martinistr. 52, D-20246 Hamburg, Germany.

Endothelial dysfunction in the setting of cardiovascular risk factors, such as hypercholesterolaemia, hypertension, diabetes mellitus and chronic smoking, as well as in the setting of heart failure, has been shown to be at least partly dependent on the production of reactive oxygen species in endothelial and/or smooth muscle cells and the adventitia, and the subsequent decrease in vascular bioavailability of NO. Superoxide-producing enzymes involved in increased oxidative stress within vascular tissue include NAD(P)H-oxidase, xanthine oxidase and endothelial nitric oxide synthase in an uncoupled state. Recent studies indicate that endothelial dysfunction of peripheral and coronary resistance and conductance vessels represents a strong and independent risk factor for future cardiovascular events. Read More

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April 2005
3 Reads