M5 L1 Cell Signalling
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Extracellular Adenosine Triphosphate and Adenosine in Cancer
Oncogene (2010) 29, 5346–5358 & 2010 Macmillan Publishers Limited All rights reserved 0950-9232/10 www.nature.com/onc REVIEW Extracellular adenosine triphosphate and adenosine in cancer J Stagg and MJ Smyth Cancer Immunology Program, Sir Donald and Lady Trescowthick Laboratories, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia Adenosine triphosphate (ATP) is actively released in the mulated the hypothesis of purinergic neurotransmission extracellular environment in response to tissue damage (Burnstock, 1972). Burnstock’s hypothesis that ATP and cellular stress. Through the activation of P2X and could be released by cells to perform intercellular P2Y receptors, extracellular ATP enhances tissue repair, signaling was initially met with skepticism, as it seemed promotes the recruitment of immune phagocytes and unlikely that a molecule that acts as an intracellular dendritic cells, and acts as a co-activator of NLR family, source of energy would also function as an extracellular pyrin domain-containing 3 (NLRP3) inflammasomes. messenger. Nevertheless, Burnstock pursued his work The conversion of extracellular ATP to adenosine, in and, together with Che Su and John Bevan, reported contrast, essentially through the enzymatic activity of the that ATP was also released from sympathetic nerves ecto-nucleotidases CD39 and CD73, acts as a negative- during stimulation (Su et al., 1971). Three decades later, feedback mechanism to prevent excessive immune responses. following the cloning and characterization of ATP and Here we review the effects of extracellular ATP and adenosine adenosine cell surface receptors, purinergic signaling is a on tumorigenesis. First, we summarize the functions of well-established concept and constitutes an expanding extracellular ATP and adenosine in the context of tumor field of research in health and disease, including cancer immunity. -
Lipid Metabolic Reprogramming: Role in Melanoma Progression and Therapeutic Perspectives
cancers Review Lipid metabolic Reprogramming: Role in Melanoma Progression and Therapeutic Perspectives 1, 1, 1 2 1 Laurence Pellerin y, Lorry Carrié y , Carine Dufau , Laurence Nieto , Bruno Ségui , 1,3 1, , 1, , Thierry Levade , Joëlle Riond * z and Nathalie Andrieu-Abadie * z 1 Centre de Recherches en Cancérologie de Toulouse, Equipe Labellisée Fondation ARC, Université Fédérale de Toulouse Midi-Pyrénées, Université Toulouse III Paul-Sabatier, Inserm 1037, 2 avenue Hubert Curien, tgrCS 53717, 31037 Toulouse CEDEX 1, France; [email protected] (L.P.); [email protected] (L.C.); [email protected] (C.D.); [email protected] (B.S.); [email protected] (T.L.) 2 Institut de Pharmacologie et de Biologie Structurale, CNRS, Université Toulouse III Paul-Sabatier, UMR 5089, 205 Route de Narbonne, 31400 Toulouse, France; [email protected] 3 Laboratoire de Biochimie Métabolique, CHU Toulouse, 31059 Toulouse, France * Correspondence: [email protected] (J.R.); [email protected] (N.A.-A.); Tel.: +33-582-7416-20 (J.R.) These authors contributed equally to this work. y These authors jointly supervised this work. z Received: 15 September 2020; Accepted: 23 October 2020; Published: 27 October 2020 Simple Summary: Melanoma is a devastating skin cancer characterized by an impressive metabolic plasticity. Melanoma cells are able to adapt to the tumor microenvironment by using a variety of fuels that contribute to tumor growth and progression. In this review, the authors summarize the contribution of the lipid metabolic network in melanoma plasticity and aggressiveness, with a particular attention to specific lipid classes such as glycerophospholipids, sphingolipids, sterols and eicosanoids. -
Molecular and Cellular Signaling
Martin Beckerman Molecular and Cellular Signaling With 227 Figures AIP PRESS 4(2) Springer Contents Series Preface Preface vii Guide to Acronyms xxv 1. Introduction 1 1.1 Prokaryotes and Eukaryotes 1 1.2 The Cytoskeleton and Extracellular Matrix 2 1.3 Core Cellular Functions in Organelles 3 1.4 Metabolic Processes in Mitochondria and Chloroplasts 4 1.5 Cellular DNA to Chromatin 5 1.6 Protein Activities in the Endoplasmic Reticulum and Golgi Apparatus 6 1.7 Digestion and Recycling of Macromolecules 8 1.8 Genomes of Bacteria Reveal Importance of Signaling 9 1.9 Organization and Signaling of Eukaryotic Cell 10 1.10 Fixed Infrastructure and the Control Layer 12 1.11 Eukaryotic Gene and Protein Regulation 13 1.12 Signaling Malfunction Central to Human Disease 15 1.13 Organization of Text 16 2. The Control Layer 21 2.1 Eukaryotic Chromosomes Are Built from Nucleosomes 22 2.2 The Highly Organized Interphase Nucleus 23 2.3 Covalent Bonds Define the Primary Structure of a Protein 26 2.4 Hydrogen Bonds Shape the Secondary Structure . 27 2.5 Structural Motifs and Domain Folds: Semi-Independent Protein Modules 29 xi xü Contents 2.6 Arrangement of Protein Secondary Structure Elements and Chain Topology 29 2.7 Tertiary Structure of a Protein: Motifs and Domains 30 2.8 Quaternary Structure: The Arrangement of Subunits 32 2.9 Many Signaling Proteins Undergo Covalent Modifications 33 2.10 Anchors Enable Proteins to Attach to Membranes 34 2.11 Glycosylation Produces Mature Glycoproteins 36 2.12 Proteolytic Processing Is Widely Used in Signaling 36 2.13 Reversible Addition and Removal of Phosphoryl Groups 37 2.14 Reversible Addition and Removal of Methyl and Acetyl Groups 38 2.15 Reversible Addition and Removal of SUMO Groups 39 2.16 Post-Translational Modifications to Histones . -
Camp Receptor Protein–Camp Plays a Crucial Role in Glucose–Lactose Diauxie by Activating the Major Glucose Transporter Gene in Escherichia Coli
Proc. Natl. Acad. Sci. USA Vol. 94, pp. 12914–12919, November 1997 Biochemistry cAMP receptor protein–cAMP plays a crucial role in glucose–lactose diauxie by activating the major glucose transporter gene in Escherichia coli KEIKO KIMATA*, HIDEYUKI TAKAHASHI*, TOSHIFUMI INADA*, PIETER POSTMA†, AND HIROJI AIBA*‡ *Department of Molecular Biology, School of Science, Nagoya University, Chikusa, Nagoya 464-01, Japan; and †E. C. Slater Institute, BioCentrum, University of Amsterdam, Plantage Muidergracht 12, 1018 TV Amsterdam, The Netherlands Communicated by Sydney Kustu, University of California, Berkeley, CA, September 17, 1997 (received for review May 2, 1997) ABSTRACT The inhibition of b-galactosidase expression certain conditions, for example, when added to cells growing in a medium containing both glucose and lactose is a typical on a poor carbon source such as glycerol or succinate (6, 7). example of the glucose effect in Escherichia coli. We studied the Glucose is thought to reduce cAMP level by decreasing the glucose effect in the lacL8UV5 promoter mutant, which is phosphorylated form of enzyme IIAGlc, which is proposed to independent of cAMP and cAMP receptor protein (CRP). A be involved in the activation of adenylate cyclase (3–5). strong inhibition of b-galactosidase expression by glucose and Glucose also is known to reduce the CRP level through the a diauxic growth were observed when the lacL8UV5 cells were autoregulation of the crp gene (7–10). grown on a glucose–lactose medium. The addition of isopropyl When E. coli finds both glucose and lactose in the medium, b-D-thiogalactoside to the culture medium eliminated the it preferentially uses the glucose, and the use of lactose is glucose effect. -
GENE REGULATION Differences Between Prokaryotes & Eukaryotes
GENE REGULATION Differences between prokaryotes & eukaryotes Gene function Description of Prokaryotic Chromosome and E.coli Review Differences between Prokaryotic & Eukaryotic Chromosomes Four differences Eukaryotic Chromosomes Form Length in single human chromosome Length in single diploid cell Proteins beside histones Proportion of DNA that codes for protein in prokaryotes eukaryotes humans Regulation of Gene Expression in Prokaryotes Terms promoter structural gene operator operon regulator repressor corepressor inducer The lac operon - Background E.coli behavior presence of lactose and absence of lactose behavior of mutants outcome of mutants The Lac operon Regulates production of b-galactosidase http://www.sumanasinc.com/webcontent/animations/content/lacoperon.html The trp operon Regulates the production of the enzyme for tryptophan synthesis http://bcs.whfreeman.com/thelifewire/content/chp13/1302002.html General Summary During transcription, RNA remains briefly bound to the DNA template Structural genes coding for polypeptides with related functions often occur in sequence Two kinds of regulatory control positive & negative General Summary Regulatory efficiency is increased because mRNA is translated into protein immediately and broken down rapidly. 75 different operons comprising 260 structural genes in E.coli Gene Regulation in Eukaryotes some regulation occurs because as little as one % of DNA is expressed Gene Expression and Differentiation Characteristic proteins are produced at different stages of differentiation producing cells with their own characteristic structure and function. Therefore not all genes are expressed at the same time As differentiation proceeds, some genes are permanently “turned” off. Example - different types of hemoglobin are produced during development and in adults. DNA is expressed at a precise time and sequence in time. -
Multifaceted Effects of Extracellular Adenosine Triphosphate and Adenosine in the Tumor–Host Interaction and Therapeutic Perspectives
Multifaceted Effects of Extracellular Adenosine Triphosphate and Adenosine in the Tumor–Host Interaction and Therapeutic Perspectives The Harvard community has made this article openly available. Please share how this access benefits you. Your story matters Citation de Andrade Mello, Paola, Robson Coutinho-Silva, and Luiz Eduardo Baggio Savio. 2017. “Multifaceted Effects of Extracellular Adenosine Triphosphate and Adenosine in the Tumor–Host Interaction and Therapeutic Perspectives.” Frontiers in Immunology 8 (1): 1526. doi:10.3389/fimmu.2017.01526. http://dx.doi.org/10.3389/ fimmu.2017.01526. Published Version doi:10.3389/fimmu.2017.01526 Citable link http://nrs.harvard.edu/urn-3:HUL.InstRepos:34493041 Terms of Use This article was downloaded from Harvard University’s DASH repository, and is made available under the terms and conditions applicable to Other Posted Material, as set forth at http:// nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of- use#LAA REVIEW published: 14 November 2017 doi: 10.3389/fimmu.2017.01526 Multifaceted Effects of Extracellular Adenosine Triphosphate and Adenosine in the Tumor–Host Interaction and Therapeutic Perspectives Paola de Andrade Mello1, Robson Coutinho-Silva 2* and Luiz Eduardo Baggio Savio2* 1 Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States, 2Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil Cancer is still one of the world’s most pressing health-care challenges, leading to a high number of deaths worldwide. Immunotherapy is a new developing therapy that Edited by: boosts patient’s immune system to fight cancer by modifying tumor–immune cells Salem Chouaib, interaction in the tumor microenvironment (TME). -
What Makes the Lac-Pathway Switch: Identifying the Fluctuations That Trigger Phenotype Switching in Gene Regulatory Systems
What makes the lac-pathway switch: identifying the fluctuations that trigger phenotype switching in gene regulatory systems Prasanna M. Bhogale1y, Robin A. Sorg2y, Jan-Willem Veening2∗, Johannes Berg1∗ 1University of Cologne, Institute for Theoretical Physics, Z¨ulpicherStraße 77, 50937 K¨oln,Germany 2Molecular Genetics Group, Groningen Biomolecular Sciences and Biotechnology Institute, Centre for Synthetic Biology, University of Groningen, Nijenborgh 7, 9747 AG, Groningen, The Netherlands y these authors contributed equally ∗ correspondence to [email protected] and [email protected]. Multistable gene regulatory systems sustain different levels of gene expression under identical external conditions. Such multistability is used to encode phenotypic states in processes including nutrient uptake and persistence in bacteria, fate selection in viral infection, cell cycle control, and development. Stochastic switching between different phenotypes can occur as the result of random fluctuations in molecular copy numbers of mRNA and proteins arising in transcription, translation, transport, and binding. However, which component of a pathway triggers such a transition is gen- erally not known. By linking single-cell experiments on the lactose-uptake pathway in E. coli to molecular simulations, we devise a general method to pinpoint the particular fluctuation driving phenotype switching and apply this method to the transition between the uninduced and induced states of the lac genes. We find that the transition to the induced state is not caused only by the single event of lac-repressor unbinding, but depends crucially on the time period over which the repressor remains unbound from the lac-operon. We confirm this notion in strains with a high expression level of the repressor (leading to shorter periods over which the lac-operon remains un- bound), which show a reduced switching rate. -
Cell Signaling and Regulation of Metabolism Objectives
Cell Signaling and Regulation of Metabolism Objectives By the end of this lecture, students are expected to: • Differentiate different steps in signaling pathways • Describe the second messenger systems • Recognize the function of signaling pathways for • Signal transmission • Amplification • Discuss the role of signaling pathways in regulation and integration of metabolism No cell lives in isolation • Cells communicate with each other • Cells send and receive information (signals) • Information is relayed within cell to produce a response Signaling Process • Recognition of signal – Receptors • Transduction – Change of external signal into intracellular message with amplification and formation of second messenger • Effect – Modification of cell metabolism and function General Signaling Pathway Signaling Cascades Recognition • Performed by receptors • Ligand will produce response only in cells that have receptors for this particular ligand • Each cell has a specific set of receptors Different Responses to the Same Signaling Molecule. (A) Different Cells Different Responses to the Same Signaling Molecule. (B) One Cell but, Different Pathways Hypoglycemia Glucagon secretion Hepatocyte: Glucagon/receptor binding Second messenger: cAMP Response: Enzyme phosphorylation P P Glycogen synthase Glycogen phosphorylase (Inactive form) (Active form) Inhibition of glycogenesis Stimulation of glycogenolysis GTP-Dependant Regulatory Proteins (G-Proteins) G-Proteins: Trimeric membrane proteins (αβγ) G-stimulatory (Gs) and G-inhibitory (Gi) binds to GTP/GDP -
I = Chpt 15. Positive and Negative Transcriptional Control at Lac BMB
BMB 400 Part Four - I = Chpt 15. Positive and Negative Transcriptional Control at lac B M B 400 Part Four: Gene Regulation Section I = Chapter 15 POSITIVE AND NEGATIVE CONTROL SHOWN BY THE lac OPERON OF E. COLI A. Definitions and general comments 1. Operons An operon is a cluster of coordinately regulated genes. It includes structural genes (generally encoding enzymes), regulatory genes (encoding, e.g. activators or repressors) and regulatory sites (such as promoters and operators). 2. Negative versus positive control a. The type of control is defined by the response of the operon when no regulatory protein is present. b. In the case of negative control, the genes in the operon are expressed unless they are switched off by a repressor protein. Thus the operon will be turned on constitutively (the genes will be expressed) when the repressor in inactivated. c. In the case of positive control, the genes are expressed only when an active regulator protein, e.g. an activator, is present. Thus the operon will be turned off when the positive regulatory protein is absent or inactivated. Table 4.1.1. Positive vs. negative control BMB 400 Part Four - I = Chpt 15. Positive and Negative Transcriptional Control at lac 3. Catabolic versus biosynthetic operons a. Catabolic pathways catalyze the breakdown of nutrients (the substrate for the pathway) to generate energy, or more precisely ATP, the energy currency of the cell. In the absence of the substrate, there is no reason for the catabolic enzymes to be present, and the operon encoding them is repressed. In the presence of the substrate, when the enzymes are needed, the operon is induced or de-repressed. -
Teaching Gene Regulation in the High School Classroom, AP Biology, Stefanie H
Wofford College Digital Commons @ Wofford Arthur Vining Davis High Impact Fellows Projects High Impact Curriculum Fellows 4-30-2014 Teaching Gene Regulation in the High School Classroom, AP Biology, Stefanie H. Baker Wofford College, [email protected] Marie Fox Broome High School Leigh Smith Wofford College Follow this and additional works at: http://digitalcommons.wofford.edu/avdproject Part of the Biology Commons, and the Genetics Commons Recommended Citation Baker, Stefanie H.; Fox, Marie; and Smith, Leigh, "Teaching Gene Regulation in the High School Classroom, AP Biology," (2014). Arthur Vining Davis High Impact Fellows Projects. Paper 22. http://digitalcommons.wofford.edu/avdproject/22 This Article is brought to you for free and open access by the High Impact Curriculum Fellows at Digital Commons @ Wofford. It has been accepted for inclusion in Arthur Vining Davis High Impact Fellows Projects by an authorized administrator of Digital Commons @ Wofford. For more information, please contact [email protected]. High Impact Fellows Project Overview Project Title, Course Name, Grade Level Teaching Gene Regulation in the High School Classroom, AP Biology, Grades 9-12 Team Members Student: Leigh Smith High School Teacher: Marie Fox School: Broome High School Wofford Faculty: Dr. Stefanie Baker Department: Biology Brief Description of Project This project sought to enhance high school students’ understanding of gene regulation as taught in an Advanced Placement Biology course. We accomplished this by designing and implementing a lab module that included a pre-lab assessment, a hands-on classroom experiment, and a post-lab assessment in the form of a lab poster. Students developed lab skills while simultaneously learning about course content. -
The Regulatory Role of Key Metabolites in the Control of Cell Signaling
biomolecules Review The Regulatory Role of Key Metabolites in the Control of Cell Signaling Riccardo Milanesi, Paola Coccetti * and Farida Tripodi Department of Biotechnology and Biosciences, University of Milano-Bicocca, 20126 Milan, Italy; [email protected] (R.M.); [email protected] (F.T.) * Correspondence: [email protected]; Tel.: +39-02-6448-3521 Received: 8 May 2020; Accepted: 3 June 2020; Published: 5 June 2020 Abstract: Robust biological systems are able to adapt to internal and environmental perturbations. This is ensured by a thick crosstalk between metabolism and signal transduction pathways, through which cell cycle progression, cell metabolism and growth are coordinated. Although several reports describe the control of cell signaling on metabolism (mainly through transcriptional regulation and post-translational modifications), much fewer information is available on the role of metabolism in the regulation of signal transduction. Protein-metabolite interactions (PMIs) result in the modification of the protein activity due to a conformational change associated with the binding of a small molecule. An increasing amount of evidences highlight the role of metabolites of the central metabolism in the control of the activity of key signaling proteins in different eukaryotic systems. Here we review the known PMIs between primary metabolites and proteins, through which metabolism affects signal transduction pathways controlled by the conserved kinases Snf1/AMPK, Ras/PKA and TORC1. Interestingly, PMIs influence also the mitochondrial retrograde response (RTG) and calcium signaling, clearly demonstrating that the range of this phenomenon is not limited to signaling pathways related to metabolism. Keywords: Snf1/AMPK/SnRK1; Ras/PKA; TORC1; RTG; calcium; glucose; glycolysis; TCA; amino acids; protein-metabolite interaction 1. -
(CRP) on Porin Genes and Its Own Gene in Yersinia Pestis
Gao et al. BMC Microbiology 2011, 11:40 http://www.biomedcentral.com/1471-2180/11/40 RESEARCHARTICLE Open Access Regulatory effects of cAMP receptor protein (CRP) on porin genes and its own gene in Yersinia pestis He Gao1†, Yiquan Zhang1†, Lin Yang1,2, Xia Liu1,2, Zhaobiao Guo1, Yafang Tan1, Yanping Han1, Xinxiang Huang2, Dongsheng Zhou1*, Ruifu Yang1* Abstract Background: The cAMP receptor protein (CRP) is a global bacterial regulator that controls many target genes. The CRP-cAMP complex regulates the ompR-envZ operon in E. coli directly, involving both positive and negative regulations of multiple target promoters; further, it controls the production of porins indirectly through its direct action on ompR-envZ. Auto-regulation of CRP has also been established in E. coli. However, the regulation of porin genes and its own gene by CRP remains unclear in Y. pestis. Results: Y. pestis employs a distinct mechanism indicating that CRP has no regulatory effect on the ompR-envZ operon; however, it stimulates ompC and ompF directly, while repressing ompX. No transcriptional regulatory association between CRP and its own gene can be detected in Y. pestis, which is also in contrast to the fact that CRP acts as both repressor and activator for its own gene in E. coli. It is likely that Y. pestis OmpR and CRP respectively sense different signals (medium osmolarity, and cellular cAMP levels) to regulate porin genes independently. Conclusion: Although the CRP of Y. pestis shows a very high homology to that of E. coli, and the consensus DNA sequence recognized by CRP is shared by the two bacteria, the Y.