Table Of ContentMOLECULAR BIOLOGY
An International Series of Monographs and Textbooks
Editors: BERNARD HORECKER, NATHAN O. KAPLAN, JULIUS MARMUR, AND
HAROLD A. SCHERAGA
A complete list of titles in this series appears at the end of this volume.
ADP-Ribosylation
Reactions
Biology and Medicine
Edited by
OSAMU HAYAISHI
KUNIHIRO UEDA
Department of Medical Chemistry
Kyoto University, Faculty of Medicine
Yoshida, Sakyo-ku, Kyoto, Japan
1982
ACADEMIC PRESS
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Library of Congress Cataloging in Publication Data
Main entry under title:
ADP-ribosylation reactions.
(Molecular biology series)
Includes index.
1. Adenosine diphosphate ribose. I. Hayaishi, Osamu,
Date. II. Ueda, Kunihiro, Date.
III. Title: ADP -ribosylation reactions. IV. Series.
[DNLM: 1. Nucleoside diphosphate sugars—Metabolism.
QU 58 A241]
QP625.A29A36 574.19'245 82-6792
ISBN 0-12-333660-0 AACR2
PRINTED IN THE UNITED STATES OF AMERICA
82 83 84 85 9 8 7 6 5 4 3 2 1
Contributors
Numbers in parentheses indicate the pages on which the authors' contributions begin.
Peter Adamietz (77, 207), Institut fur Physiologische Chemie, Universitat
Hamburg, Universitats-Krankenhaus Eppendorf, 2000 Hamburg 20, West
Germany
Remi J. Aubin (323), Departement de Biologie, Faculte des Sciences, Univer-
site de Sherbrooke, Sherbrooke, Quebec J IK 2R1, Canada
Nathan A. Berger (547), Hematology and Oncology Division, the Jewish Hos
pital of St. Louis, Washington University School of Medicine, St. Louis,
Missouri 63178
Reinhard Bredehorst (207, 305), Universitat Hamburg, Universitats-Kranken
haus Eppendorf, Kerninstitut fur Medizinische Mikrobiologie und Immu
nologic, 2000 Hamburg, West Germany
Yvon Brousseau (323), Departement de Biologie, Faculte des Sciences, Univer-
site de Sherbrooke, Sherbrooke, Quebec J IK 2R1, Canada
Luis O. Burzio (103), Instituto de Bioquimica, Universidad Austral de Chile,
Casilla 567, Valdivia, Chile
Tauseef Butt (173), Developmental Biochemistry Section, Laboratory of Nutri
tion and Endocrinology, National Institute of Arthritis, Diabetes, Digestive,
and Kidney Diseases, National Institutes of Health, Bethesda, Maryland
20205
Arnold I. Caplan (389), Biology Department, Case Western Reserve Univer
sity, Cleveland, Ohio 44106
C. A. Carter (221), Department of Microbiology, School of Basic Health Sci
ences, Health Sciences Center, State University of New York at Stony
Brook, Stony Brook, New York 11794
Barry W. Cherney (389), Biology Department, Case Western Reserve Univer
sity, Cleveland, Ohio 44106
Jonathan J. Cohen1 (547), Hematology and Oncology Division, The Jewish
'Present address: Department of Medicine, University of Miami, School of Medicine, Miami,
Florida 33101.
xix
XX Contributors
Hospital of St. Louis, Washington University School of Medicine, St.
Louis, Missouri 63178
R. John Collier (575), Department of Microbiology and the Molecular Biology
Institute, University of California, Los Angeles, California 90024
Than V. Dam (323), Departement de Biologie, Faculte des Sciences, Universite
de Sherbrooke, Sherbrooke, Quebec J IK 2R1, Canada
Guy Faribault (323), Departement de Biologie, Faculte des Sciences, Univer
site de Sherbrooke, Sherbrooke, Quebec J IK 2R1, Canada
Ari M. Ferro (19), Department of Biology, University of Utah, Salt Lake City,
Utah 84112
Q. Perveen Ghani (439), Cardiovascular Research Institute and Departments of
Medicine, University of California, San Francisco, and Veterans Admin
istration Medical Center, San Francisco, California 94121
D. Michael Gill (593), Department of Molecular Biology and Microbiology,
Tufts University School of Medicine, Boston, Massachusetts 02111
Osamu Hayaishi (3, 117, 279, 339, 561), Department of Medical Chemistry,
Kyoto University, Faculty of Medicine, Yoshida, Sakyo-ku, Kyoto 606,
Japan
Helmuth Hilz (207, 305), Institute fur Physiologische Chemie, Universitat
Hamburg, 2000 Hamburg 20, West Germany
Milton Hollenberg (439), Cardiovascular Research Institute and Departments of
Medicine, University of California, San Francisco, and Veterans Admin
istration Medical Center, San Francisco, California 94121
Barbara H. Iglewski (661), Department of Microbiology and Immunology,
Oregon Health Sciences University, Portland, Oregon 97201
Kouichi Ikai2 (339), Department of Dermatology, Kyoto University, Faculty of
Medicine, Yoshida, Sakyo-ku, Kyoto 606, Japan
Tomoya Kamiya (157), Department of Biochemistry, Nara Medical University,
Shijo-cho, Kashihara 634, Nara, Japan
Yoshiyuki Kanai (533), Department of Molecular Oncology, Institute of Medi
cal Science, University of Tokyo, Shirokanedai 4-6-1, Minato-ku, Tokyo
108, Japan
Masashi Kawaichi (117), Department of Medical Chemistry, Kyoto University,
Faculty of Medicine, Yoshida, Sakyo-ku, Kyoto 606, Japan
William R. Kidwell (373), Cell Cycle Regulation Section, Laboratory of Pa
thophysiology, National Cancer Institute, National Institutes of Health,
Bethesda, Maryland 20205
Eva Kirsten (193), Cardiovascular Research Institute, Department of Phar
macology, Biochemistry and Biophysics, University of California at San
Francisco, San Francisco, California 94143
2Present address: Department of Dermatology, School of Medicine, Yale University, New Haven,
Connecticut 06510.
Contributors xxi
Akihide Kitamura (465), Department of Biochemistry, Shimane Medical Uni
versity, Izumo, Shimane-ken 693, Japan
Samuel S. Koide (361), Population Council, Center for Biomedical Research,
The Rockefeller University, New York, New York 10021
Ernest Kun (193), Cardiovascular Research Institute, Department of Phar
macology, Biochemistry and Biophysics, University of California at San
Francisco, San Francisco, California 94143
Β. Y. Lin (221), Department of Microbiology, School of Basic Health Sciences,
Health Sciences Center, State University of New York at Stony Brook,
Stony Brook, New York 11794
Paul Mandel (287), Centre de Neurochimie du CNRS, 67084 Strasbourg
Cedex, France
Julien G. Miclette (323), Departement de Biologie, Faculte des Sciences, Uni-
versite de Sherbrooke, Sherbrooke, Quebec J IK 2R1, Canada
Ronald J. Midura (389), Biology Department, Case Western Reserve Univer
sity, Cleveland, Ohio 44106
Masanao Miwa (43, 263), Virology Division, National Cancer Center Research
Institute, Tsukiji 5-1-1, Chuo-ku, Tokyo 104, Japan
Joel Moss (623, 637), Laboratory of Cellular Metabolism, National Heart,
Lung, and Blood Institute, National Institutes of Health, Bethesda, Mary
land 20205
Takashi Murachi (521), Department of Clinical Science, Kyoto University,
Faculty of Medicine, Yoshida, Sakyo-ku, Kyoto 606, Japan
Claude Niedergang (287), Centre de Neurochimie du CNRS, 67084 Strasbourg
Cedex, France
Nancy Nolan (373), Cell Cycle Regulation Section, Laboratory of Pathophysiol
ogy, National Cancer Institute, National Institutes of Health, Bethesda,
Maryland 20205
Jun Oka (279), Department of Medical Chemistry, Kyoto University, Faculty of
Medicine, Yoshida, Sakyo-ku, Kyoto 606, Japan
Baldomero M. Olivera (19), Department of Biology, University of Utah, Salt
Lake City, Utah 84112
Colin K. Pearson (407, 423), Department of Biochemistry, University of Aber
deen, Marischal College, Aberdeen AB9 IAS, Scotland
Frank W. Perrella (451), McArdle Laboratory for Cancer Research, Depart
ment of Oncology, Medical School, University of Wisconsin, Madison,
Wisconsin 53706
Guy G. Poirier (323), Departement de Biologie, Faculte des Sciences, Univer-
site de Sherbrooke, Sherbrooke, Quebec J IK 2R1, Canada
John W. Porteous (423), Department of Biochemistry, University of Aberdeen,
Marischal College, Aberdeen AB9 IAS, Scotland
R. O. Pozzatti (221), Department of Microbiology, School of Basic Health
xxii Contributors
Sciences, Health Sciences Center, State University of New York at Stony
Brook, Stony Brook, New York 11794
D. Rickwood (253), Department of Biology, University of Essex, Colchester,
England
Sydney Shall (477), Cell and Molecular Biology Laboratory, University of
Sussex, Brighton, East Sussex, BN1 9QG, England
Makoto Shimoyama (465), Department of Biochemistry, Shimane Medical
University, Izumo, Shimane-ken 693, Japan
Romuald Skorko (647), Department of Biochemistry, University of Gdansk,
Gdansk 80-822, Poland
Mark Smulson (173), Department of Biochemistry, Georgetown University
School of Medicine and Dentistry, Washington, D.C. 20007
Peter R. Stone3 (373), Cell Cycle Regulation Section, Laboratory of Pa
thophysiology, National Cancer Institute, National Institutes of Health,
Bethesda, Maryland 20205
Takashi Sugimura (43, 263, 533), National Cancer Center Research Institute,
Tsukiji, Chuo-ku, Tokyo 104, Japan
Robert J. Suhadolnik (65), Department of Biochemistry, School of Medicine,
Temple University, Philadelphia, Pennsylvania 19140
Yoshinori Tanigawa (465), Department of Biochemistry, Shimane Medical
University, Izumo, Shimane-ken 693, Japan
Michael R. Thompson4 (661), Department of Microbiology and Immunology,
Oregon Health Sciences University, Portland, Oregon 97201
Kunihiro Ueda (3, 117, 279, 339, 561), Department of Medical Chemistry,
Kyoto University, Faculty of Medicine, Yoshida, Sakyo-ku, Kyoto 606,
Japan
Martha Vaughan (623, 637), Laboratory of Cellular Metabolism, National
Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda,
Maryland 20205
Karl G. Wagner (241), Molekularbiologie Abteilung, Gesellschaft fur Bio-
technologische Forschung mbH, Mascheroder Weg 1, D-3300 Braunsch-
weig-Stockheim, West Germany
Klaus Wielckens (207, 305), Universitat Hamburg, Universitats-Krankenhaus
Eppendorf, Kerninsitut fur Medizinische Mikrobiologie und Immunologic,
2000 Hamburg, West Germany
Lothar Willmitzer (241), Max-Planck Institute fur Zuchtungsforschung, Koln,
West Germany
Koichiro Yoshihara (157), Department of Biochemistry, Nara Medical Univer
sity, Shijo-cho, Kashihara 634, Nara, Japan
3Present address: 71 Grasmere Road, Blackpool Lancashire FY1 SHP, England.
4Present address: Department of Medicine, University of Cincinnati Medical School, Cincinnati,
Ohio 45220.
Preface
It has been about 15 years since poly(ADP-ribose) was discovered and was
shown to be a unique homopolymer covalently attached to chromosomal pro
teins. Since then, detailed studies on the structure, metabolism, enzymology, as
well as physiological function related to this unique polymer, were undertaken in
a number of laboratories throughout the world. A growing body of evidence now
suggests that poly(ADP-ribose) is ubiquitously distributed in eukaryotes and is
involved in the regulation of DNA metabolism. Parallel to these studies, there is
now a considerable amount of evidence indicating that mono(ADP-ribosyl)ation
is a rather common way by which proteins are covalently modified and their
biological functions regulated.
During the past 15 years, numerous international symposia have been held and
many review articles published. However, a comprehensive and systematic trea
tise has not been available. We have, therefore, undertaken the editing of this
volume in an attempt to summarize what is currently known of poly(ADP-ribose)
and ADP-ribosylation of proteins by expert investigators in each subject and to
outline future prospects of this fascinating area of research. The editors are
grateful to all the contributors for providing excellent articles. Thanks are also
due to Ms. Mariko Ohara, Drs. M. Kawaichi, and J. Oka for assistance with the
preparation of this volume.
Finally, we wish to acknowledge the support of the study group of poly (ADP-
ribose) and ADP-ribosylation of proteins by the Cancer Research Fund of the
Ministry of Education, Science and Culture of Japan. This study group was
organized about 15 years ago and has played a major role in the development of
this field of research in Japan. One of us (O.H.) recalls with great pleasure, free
and friendly exchange of ideas and information among the members of this group
during all these years and particular gratitude is extended to Drs. T. Sugimura,
M. Miwa, and associates for enthusiastic cooperation.
Osamu Hayaishi
Kunihiro Ueda
xxiii
Chapter 1
Poly- and
Mono( ADP- ribosyDation
Reactions: Their
Significance in
Molecular Biology
OSAMU HAYAISHI AND
KUNIHIRO UEDA
I. Prologue 3
II. Discovery of Poly(ADP-ribose) 5
III. ADP-Ribosylation of Proteins 6
A. Poly(ADP-ribosyl)ation of Proteins 7
B. Mono(ADP-ribosyl)ation of Proteins 8
IV. Prospects 11
References 14
I. PROLOGUE
Poly(ADP-ribose) and the ADP-ribosylation of proteins constitute a novel type
of covalent modification of proteins, and are involved in the modulation of
activities of various enzymes as well as structural proteins. During the last few
years, these reactions have attracted the attention of a number of molecular
biologists because they are ubiquitously distributed in nature and are implicated
ADP-RIBOSYLATION REACTIONS 3
Copyright © 1982 by Academic Press, Inc.
All rights of reproduction in any form reserved.
ISBN 0-12-333660-0
4 Osamu Hayaishi and Kunihiro Ueda
in the regulation of cell proliferation, protein synthesis, and DNA as well as
RNA metabolism. This book is an attempt to provide the reader with up-to-date
information concerning the biochemical and physiological aspects of ADP-
ribosylation reactions in general. By way of introduction, we shall first describe
briefly historical aspects of the discovery of poly(ADP-ribose) and then present
an overall review of poly- and mono(ADP-ribosyl)ation reactions. Finally a few
remarks will be made with regard to the future prospects of these unique bio
chemical reactions, in which NAD, a respiratory coenzyme, is utilized as an
ADP-ribosyl donor.
The discovery of pyridine nucleotide coenzymes dates back to the first decade
of this century when Harden and Young (1904) found that a yeast extract lost its
ability to ferment glucose to ethyl alcohol when the extract was dialyzed, and
that the activity was restored by the addition of the dialyzable material. The latter
compound was named cozymase and was classified as a coenzyme, a more
general term to denote substances of low molecular weight and which are essen
tial for enzyme activity. Studies on the chemical identity of cozymase were
initiated by von Euler, who reported the presence of adenosine 5'-phosphate in
this compound. Soon afterward, Warburg discovered that mammalian
erythrocytes contain a thermostable, dialyzable factor which is required for the
oxidation of glucose 6-phosphate to 6-phosphogluconate. Warburg and Christian
(1935) isolated this cofactor from erythrocytes and established that it is com
posed of one molecule of adenine, two pentose units, three equivalents of phos
phoric acid, and one molecule of the amide of nicotinic acid. This demonstration
of the presence of nicotinamide in this compound was followed by the discovery
in 1937 that nicotinic acid was effective for the prevention and treatment of
pellagra (see Sebrell, 1981). The discovery of nicotinamide in the Warburg's
compound led von Euler to look for the presence of nicotinamide in his prepara
tion and, on the basis of work done by von Euler, Schlenk, and associates, the
chemical structure of cozymase was established (Fig. 1).
In light of the chemical structure of this coenzyme, it was soon being referred
to as diphosphopyridine nucleotide, abbreviated as DPN, while Warburg's co
enzyme was referred to as triphosphopyridine nucleotide (TPN). Later the Inter-
Fig. 1. Chemical structure of cozymase.
