P1: JZZ 0521836549agg.xml CB856/Henderson 0 521 83654 9 August 27, 1956 18:0 This page intentionally left blank P1: JZZ 0521836549agg.xml CB856/Henderson 0 521 83654 9 August 27, 1956 18:0 Molecular Chaperones and Cell Signalling This book reviews current understanding of the biological roles of extracellular molecular chaperones. It provides an overview of the structure and function of molecular chaperones, their role in the cellular response to stress, and their dispo- sition within the cell. It also questions the basic paradigm of molecular chaperone biology – that these proteins are, first and foremost, protein-folding molecules. The current paradigms of protein secretion are reviewed, and the evolving concept of proteins (such as molecular chaperones) as multi-functional molecules, “moonlight- ing proteins,” is discussed. The role of exogenous molecular chaperones as cell regula- tors is examined, and the physiological and pathophysiological roles that molecular chaperones play are described. In the final section, the potential therapeutic use of molecular chaperones is described, and in the final chapter, the crystal ball is brought out and the question – what does the future hold for the extracellular biology of molecular chaperones – is asked. Brian Henderson is Professor of Cell Biology at the Eastman Dental Institute, University College London, and Head of the Cellular Microbiology Research Group. His major research interests are concerned with bacterial interactions with the host and how such interactions control inflammation and associated tissue destruction. It is through these studies that he identified that molecular chaperones are bacterial virulence factors and started his interest in the direct immunomodulatory actions of cell stress proteins. A. Graham Pockley is Professor of Immunobiology at the University of Sheffield Medical School and is Head of the Immunobiology Research Unit. Professor Pockley has long-standing interests in the immunobiology of transplant rejection, and his unit is currently focussed on research relating to the biology and immunotherapeutic potential of heat shock proteins, particularly their involvement in the rejection of organ transplants and the development and progression of cardiovascular disease. i P1: JZZ 0521836549agg.xml CB856/Henderson 0 521 83654 9 August 27, 1956 18:0 ii P1: JZZ 0521836549agg.xml CB856/Henderson 0 521 83654 9 August 27, 1956 18:0 Molecular Chaperones and Cell Signalling Edited by Brian Henderson University College London A. Graham Pockley University of Sheffield iii CAMBRIDGE UNIVERSITY PRESS Cambridge, New York, Melbourne, Madrid, Cape Town, Singapore, São Paulo Cambridge University Press The Edinburgh Building, Cambridge CB2 8RU, UK Published in the United States of America by Cambridge University Press, New York www.cambridge.org Information on this title: www.cambridge.org/9780521836548 © Cambridge University Press 2005 This publication is in copyright. Subject to statutory exception and to the provision of relevant collective licensing agreements, no reproduction of any part may take place without the written permission of Cambridge University Press. First published in print format 2005 ISBN-13 978-0-511-34441-1 eBook (EBL) ISBN-10 0-511-34441-4 eBook (EBL) ISBN-13 978-0-521-83654-8 hardback ISBN-10 0-521-83654-9 hardback Cambridge University Press has no responsibility for the persistence or accuracy of urls for external or third-party internet websites referred to in this publication, and does not guarantee that any content on such websites is, or will remain, accurate or appropriate. P1: JZZ 0521836549agg.xml CB856/Henderson 0 521 83654 9 August 27, 1956 18:0 Contents Contributors page ix Preface xiii SECTION 1 MOLECULAR CHAPERONES AND THE CELL STRESS RESPONSE 1Chaperone Function: The Orthodox View 3 R. J. Ellis 2 Intracellular Disposition of Mitochondrial Molecular Chaperones: Hsp60, mHsp70, Cpn10 and TRAP-1 22 R. S. Gupta, T. Bowes, S. Sadacharan, and B. Singh SECTION 2 CHANGING PARADIGMS OF PROTEIN TRAFFICKING AND PROTEIN FUNCTION 3Novel Pathways of Protein Secretion 45 G. Chimini and A. Rubartelli 4Moonlighting Proteins: Proteins with Multiple Functions 61 C. J. Jeffery 5Molecular Chaperones: The Unorthodox View 78 B. Henderson and A. Shamaei-Tousi SECTION 3 EXTRACELLULAR BIOLOGY OF MOLECULAR CHAPERONES: MOLECULAR CHAPERONES AS CELL REGULATORS 6Cell-Cell Signalling Properties of Chaperonins 99 A. R. M. Coates and P. Tormay v P1: JZZ 0521836549agg.xml CB856/Henderson 0 521 83654 9 August 27, 1956 18:0 vi Contents 7Toll-Like Receptor-Dependent Activation of Antigen Presenting Cells by Hsp60, gp96 and Hsp70 113 R. M. Vabulas and H. Wagner 8Regulation of Signal Transduction by Intracellular and Extracellular Hsp70 133 A. Asea and S. K. Calderwood 9 Hsp72 and Cell Signalling 144 V. L. Gabai and M. Y. Sherman 10 Heat Shock Proteins, Their Cell Surface Receptors and Effect on the Immune System 160 T. Lehner, Y. Wang, T. Whittall, and L. A. Bergmeier 11 Molecular Chaperone–Cytokine Interactions at the Transcriptional Level 179 A. Stephanou and D. S. Latchman SECTION 4 EXTRACELLULAR BIOLOGY OF MOLECULAR CHAPERONES: PHYSIOLOGICAL AND PATHOPHYSIOLOGICAL SIGNALS 12 Heat Shock Protein Release and Naturally Occurring Exogenous Heat Shock Proteins 195 J. Frostegard˚ and A. G. Pockley 13 Hsp27 as an Anti-inflammatory Protein 220 K. Laudanski, A. K. De, and C. L. Miller-Graziano 14 BiP, a Negative Regulator Involved in Rheumatoid Arthritis 234 V. M. Corrigall and G. S. Panayi SECTION 5 EXTRACELLULAR BIOLOGY OF MOLECULAR CHAPERONES: MOLECULAR CHAPERONES AS THERAPEUTICS 15 Neuroendocrine Aspects of the Molecular Chaperones ADNF and ADNP 251 I. Gozes, I. Vulih, I. Spivak-Pohis, and S. Furman 16 Heat Shock Proteins Regulate Inflammation by Both Molecular and Network Cross-Reactivity 263 F. J. Quintana and I. R. Cohen 17 Heat Shock Protein Fusions: A Platform for the Induction of Antigen-Specific Immunity 288 L. Mizzen and J. Neefe P1: JZZ 0521836549agg.xml CB856/Henderson 0 521 83654 9 August 27, 1956 18:0 Contents vii 18 Molecular Chaperones as Inducers of Tumour Immunity 300 P. P. Banerjee and Z. Li SECTION 6 EXTRACELLULAR BIOLOGY OF MOLECULAR CHAPERONES: WHAT DOES THE FUTURE HOLD? 19 Gazing into the Crystal Ball: The Unfolding Future of Molecular Chaperones 321 L. E. Hightower Index 327 P1: JZZ 0521836549agg.xml CB856/Henderson 0 521 83654 9 August 27, 1956 18:0 viii P1: JZZ 0521836549agg.xml CB856/Henderson 0 521 83654 9 August 27, 1956 18:0 Contributors A. Asea S. K. Calderwood Center for Molecular Stress Response Department of Radiation Oncology Boston Medical Center and Boston Beth Israel Deaconess Medical Center University School of Medicine and Harvard Medical School Boston 21-27 Burlington Avenue Massachusetts 02118 Boston U.S.A. Massachusetts 02215 U.S.A. P. P. Banerjee Center for Immunotherapy of Cancer and Infectious Diseases G. Chimini University of Connecticut School of Centre d’Immunology de Marseille- Medicine Luminy 263 Farmington Avenue INSERM/CNRS et Universitedela´ Farmington Mediterranee´ Connecticut 06030 Parc Scientifique de Luminy U.S.A. Marseille 13288 France L. A. Bergmeier Peter Gorer Department of A. R. M. Coates Immunobiology Department of Medical Microbiology Guy’s, King’s and St. Thomas Hospital St. George’s Hospital Medical School Medical School Tooting London SE1 9RT London SW17 0RE United Kingdom United Kingdom T. Bowes Department of Biochemistry I. R. Cohen McMaster University Department of Immunology Hamilton TheWeizmann Institute of Science Ontario L8N 3Z5 Rehovot 76100 Canada Israel ix P1: JZZ 0521836549agg.xml CB856/Henderson 0 521 83654 9 August 27, 1956 18:0 x Contributors V. M. Corrigall Boston Academic Department of Massachussets 02118 Rheumatology U.S.A. GKTSchool of Medicine King’s College London I. Gozes London SE1 9RT Department of Clinical Biochemistry United Kingdom and Interdepartmental Core Facility Sackler School of Medicine A. K. De Te lAviv University Immunobiology & Stress Response Te l Aviv 69978 Laboratories Israel University of Rochester Medical Center Department of Surgery R. S. Gupta 601 Elmwood Avenue Department of Biochemistry Rochester McMaster University NewYork 14642 Hamilton U.S.A. Ontario L8N 3Z5 Canada R. J. Ellis B. Henderson Department of Biological Sciences Division of Microbial Diseases University of Warwick Eastman Dental Institute Coventry CV4 7AL University College London United Kingdom 256 Gray’s Inn Road London WC1X 8LD J. Frostegard˚ United Kingdom Unit of Rheumatology Department of Medicine and Center L. E. Hightower for Molecular Medicine Department of Molecular and Cell Karolinska Hospital Biology 171 76 Stockholm The University of Connecticut Sweden 91 North Eagle Road Storrs S. Furman Connecticut 06269 Department of Clinical Biochemistry U.S.A. and Interdepartmental Core Facility Sackler School of Medicine C. J. Jeffery Te lAviv University University of Illinois at Chicago Te l Aviv 69978 Department of Biological Sciences Israel MBRB 4252 M/C 567 900 South Ashland Avenue V. L. Gabai Chicago Department of Biochemistry Illinois 60607 Boston University School of Medicine Silvio Conte Building D. S. Latchman 715 Albany Street The Master P1: JZZ 0521836549agg.xml CB856/Henderson 0 521 83654 9 August 27, 1956 18:0 Contributors xi Birkbeck College L. Mizzen University of London Stressgen Biotechnologies Corporation Malet Street #350-4243 Glanford Avenue London WC1E 7HX Victoria United Kingdom British Columbia V8Z 4B9 Canada K. Laudanski Immunobiology & Stress Response J. Neefe Laboratories Stressgen