Cellular Senescence and Tumor Suppression PDF
Preview Cellular Senescence and Tumor Suppression
Cellular Senescence and Tumor Suppression Peter D. Adams John M. Sedivy ● Editors Cellular Senescence and Tumor Suppression Editors Peter D. Adams John M. Sedivy CRUK Beatson Labs Department of Molecular Biology University of Glasgow Cell Biology and Biochemistry Garscube Estate Brown University Switchback Road Providence, RI 02912 Glasgow, G20 8PU USA UK [email protected] [email protected] ISBN 978-1-4419-1074-5 e-ISBN 978-1-4419-1075-2 DOI 10.1007/978-1-4419-1075-2 Springer New York Dordrecht Heidelberg London Library of Congress Control Number: 2009933096 © Springer Science+Business Media, LLC 2010 All rights reserved. This work may not be translated or copied in whole or in part without the written permission of the publisher (Springer Science+Business Media, LLC, 233 Spring Street, New York, NY 10013, USA), except for brief excerpts in connection with reviews or scholarly analysis. Use in connection with any form of information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed is forbidden. The use in this publication of trade names, trademarks, service marks, and similar terms, even if they are not identified as such, is not to be taken as an expression of opinion as to whether or not they are subject to proprietary rights. Printed on acid-free paper Springer is part of Springer Science+Business Media (www.springer.com) Contents Introduction ..................................................................................................... ix John M. Sedivy Section 1 Senescence Signals 1 Telomere Biology and Biochemistry ........................................................ 3 Laura Gardano and Lea Harrington 2 Role of RecQ Helicases in Nuclear DNA Repair and Telomere Maintenance .............................................................................................. 45 Avik Ghosh, Yie Liu, and Vilhelm A. Bohr 3 Oncogene-Induced Senescence (OIS) as a Cellular Response to Oncogenic Stresses ................................................................................ 63 Véronique Bourdeau and Gerardo Ferbeyre 4 Stress-Induced Senescence ....................................................................... 85 Peter J. Hornsby Section 2 The Senescent Phenotype 5 The Secretome of Senescent Cells ............................................................ 109 Gowrishankar Banumathy and Peter D. Adams 6 Chromatin Structure in Senescent Cells ................................................. 125 Hunter W. Richards and Estela E. Medrano 7 A Comparison of Senescence in Mouse and Human Cells .................... 175 Vera Gorbunova and Andrei Seluanov v vi Contents Section 3 The Physiological Consequences of Senescence 8 Replicative Senescence as an Intrinsic Tumor-Suppressor Mechanism ............................................................................................... 201 Sandy Chang 9 Telomere Dysfunction and Senescence in Stem Cell and Tissues Aging ................................................................................... 219 Kodandaramireddy Nalapareddy and K. Lenhard Rudolph 10 Mining Cellular Senescence for Drug Targets ...................................... 235 Alan E. Bilsland and W. Nicol Keith Index ................................................................................................................. 267 Contributors Peter D. Adams CRUK Beatson Labs, University of Glasgow, Garscube Estate, Glasgow G20 8PU, UK [email protected] Gowrishankar Banumathy Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111, USA [email protected] Alan E. Bilsland Centre for Oncology and Applied Pharmacology, University of Glasgow, Cancer Research UK Beatson Laboratories, Garscube Estate, Switchback Road, Bearsden, Glasgow G61 1BD, UK [email protected] Vilhelm A. Bohr Laboratory of Molecular Gerontology, 5600 Nathan Shock Drive, Baltimore, MD 21224-6825, USA [email protected] Véronique Bourdeau Département de Biochimie, Université de Montréal, C.P. 6128, Succ. Centre-Ville, Montréal, QC, Canada H3C 3J7 [email protected] Sandy Chang, M.D., Ph.D. Assistant Professor, Unit 1006, U.T.M.D. Anderson Cancer Center, Department of Molecular Genetics, 1515 Holcombe Boulevard, Houston, TX 77030, USA [email protected] Gerardo Ferbeyre Département de Biochimie, Université de Montréal, C.P. 6128, Succ. Centre-Ville, Montréal, QC, Canada H3C 3J7 [email protected] vii viii Contributors Laura Gardano Wellcome Trust Centre for Cell Biology, University of Edinburgh, Michael Swann Building, Kings Buildings, Mayfield Road, EDINBURGH EH9 3JR [email protected] Avik Ghosh Laboratory of Molecular Gerontology, 5600 Nathan Shock Drive, Baltimore, MD 21224-6825, USA [email protected] Vera Gorbunova Department of Biology, University of Rochester, 213 Hutchison Hall, River Campus, Box 270211, Rochester, NY 14627-0211, USA [email protected] Lea Harrington Wellcome Trust Centre for Cell Biology, University of Edinburgh, Michael Swann Building, Kings Buildings, Mayfield Road, EDINBURGH EH9 3JR [email protected] Peter Hornsby Professor, Department of Physiology, Sam and Ann Barshop Inst. for Longevity and Aging Studies, University of Texas Health Science Center, 15355 Lambda Drive, STCBM Bldg., San Antonio, TX 78245, USA [email protected] W. Nicol Keith Cancer Research UK Beatson Laboratories, Centre for Oncology and Applied Pharmacology, University of Glasgow, Garscube Estate, Switchback Road, Bearsden, Glasgow G61 1BD, UK [email protected] Yie Liu Laboratory of Molecular Gerontology, 5600 Nathan Shock Drive, Baltimore, MD 21224-6825, USA [email protected] Estela E. Medrano Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA [email protected] Kodandaramireddy Nalapareddy Institute of Molecular Medicine and Max-Planck-Research-Group on Stem Cell Aging, Albert-Einstein-Allee 11, 89081 Ulm, Germany [email protected] Contributors ix Hunter W. Richards Huffington Center on Aging, Baylor College of Medicine, Houston, TX 77030, USA K.Lenhard Rudolph Institute of Molecular Medicine and Max-Planck-Research-Group on Stem Cell Aging, Albert-Einstein-Allee 11, 89081 Ulm, Germany [email protected] Andrei Seluanov Department of Biology, University of Rochester, 213 Hutchison Hall, River Campus, Box 270211, Rochester, NY 14627-0211, USA [email protected] Introduction John M. Sedivy Age-related diseases, such as malignant neoplasms, are among the leading causes of death and disability in modern societies. Two fundamental cellular aging pro- cesses have been described. One is chronological aging, and is the consequence of time-dependent changes that result from the breakdown of the balance between biosynthesis, repair and turnover. Chronological aging – an important component of which is the accumulation of damaged or otherwise dysfunctional macromole- cules – is of paramount importance in terminally differentiated cells. Replicative aging, on the other hand, reflects the inability of a cell (and thus its lineage) to sup- port the ongoing rounds of cell division. It is thus believed to be of major impor- tance in complex metazoan organisms, such as mammals, whose adult bodies depend on the extensive tissue turnover. Cell division is however a double-edged sword that needs to be tightly regulated: it counteracts chronological aging (by the simple dilution of damaged macromolecules) and leads to the genesis of new func- tional cells, while excessive replication places the organism at risk of malignant transformation. Replicative cellular aging, termed cellular senescence, was discovered in 1961 and described by Leonard Hayflick as an irreversible growth arrest triggered by the accumulation of a discrete number of cell divisions. The great majority of normal cell types from all vertebrate species display this response. The underlying cause of senescence due to replicative exhaustion is telomere shortening, a molecular count- ing mechanism that monitors elapsed cell divisions. It is now evident, however, that what had been classically described as replicative senescence is in fact a collection of interrelated states that can be triggered by distinct intrinsic and extrinsic stimuli. Although dysfunctional telomeres are sufficient to trigger senescence, and in some cases are the primary cause, it is now apparent that many types of stress, including ionizing and ultraviolet irradiation, reactive oxygen species, pharmacological agents that modify DNA or chromatin, nutrient imbalances, and even culture condi- tions can trigger a cellular senescence response. J.M. Sedivy Department of Molecular Biology, Cell Biology and Biochemistry, Brown University, Providence, R1 02912, USA e-mail: [email protected] xi
The list of books you might like
