Table Of ContentUbiquitin and
the Biology
of the Cell
Ubiquitin and
the Biology
of the Cell
Edited by
Jan-Michael Peters
Research Institute of Molecular Pathology
Vienna, Austria
J. Robin Harris
Institute of Zoology
University of Mainz
Mainz, Germany
and
Daniel Finley
Harvard Medical School
Boston, Massachusetts
Springer Science+Business Media, LLC
Library of Congress Cataloging in Publication Data
Ubiquitin and the biology of the cell / edited by Jan-Michael Peters, J. Robin Harris, and
Daniel Finley.
p. cm.
Includes bibliographical references and index.
ISBN 978-1-4899-1924-3
1. Ubiquitin. I. Peters, Jan-Michael. II. Harris, James R. III. Finley, Daniel.
QP552.U24U253 1998
572'.6—dc21 98-18550
CIP
Front cover: Structures of 20S and 26S proteasome complexes. Crystal structures of
the 20S proteasome from the archaebacterium Thermoplasma acidophilum (top) and
the yeast Saccharomyces cerevisiae (bottom) are shown as space-filling
representations. The molecules colored in yellow represent cocrystallized proteasome
inhibitor molecules (acetyl-leucyl-leucyl-norleucinal). The 26S proteasome complex
purified from oocytes of the frog Xenopus laevis (center) is shown as a correlation
average obtained from negatively stained electron micrographs. For further details see
Groll et al., Nature3Q6, 463-471 (1997); LOwe eta/., Science268, 533-539 (1995);
Peters etai, J. Mol. Biol. 234, 932-937 (1993); and Chapters 5 and 6 i n this volume.
The image of the Thermoplasma proteasome was kindly provided b y Dr. Andrei Lupas
and Dr. Wolfgang Baumeister. The other two images are reproduced with kind
permission of Macmillan Magazines Ltd. and of Academic Press Ltd.
Back cover: Yeast cells expressing K48R mutant ubiquitin in place of wild-typ e
ubiquitin. Photo courtesy of V. Chau an d D. Finley.
ISBN 978-1-4899-1924-3 ISBN 978-1-4899-1922-9 (eBook)
DOI 10.1007/978-1-4899-1922-9
©1998 Springer Science+Business Media New York
Originally published by Plenum Press, New York in 1998
Softcover reprint of the hardcover 1st edition 1998
10987654321
All rights reserved
No part of this book may be reproduced, stored in a retrieval system, or transmitted in
any form or by any means, electronic, mechanical, photocopying, microfilming,
recording, or otherwise, without written permission from the Publisher
Contributors
Wolfgang Baumeister Molekulare Strukturbiologie, Max-Planck-Institute
ftir Biochemie, D-82152 Martinsried, Germany
Jochen Beninga Department of Cell Biology, Harvard Medical School, Bos-
ton, Massachusetts 02115
C. Byrd Division of Biology, California Institute of Technology, Pasadena,
California 91125
Zhijian J. Chen ProScript, Inc., Cambridge, Massachusetts 02139
Philip Coffino Department of Microbiology and Immunology and of Medi-
cine, University of California, San Francisco, San Francisco, California
94143
I. V. Davydov Division of Biology, California Institute of Technology, Pas-
adena, California 91125
Raymond J. Deshaies Division of Biology, California Institute of Technol-
ogy, Pasadena, California 91125
R. J. Dohmen Institut flir Mikrobiologie, Heinrich-Heine-Universitat,
D-40225 Dtisseldorf, Germany
F. Du Division of Biology, California Institute of Technology, Pasadena,
California 91125
M. Ghislain Unite de Biochimie Physiologique, Universite catholique de
Louvain, B-1348 Louvain-la-Neuve, Belgium
Alfred Goldberg Department of Cell Biology, Harvard Medical School,
Boston, Massachusetts 02115
M. Gonzalez NICHD, National Institutes of Health, Bethesda, Maryland
20892-2725
S. Grigoryev Department of Biology, University of Massachusetts, Amherst,
Massachusetts 01003
Avram Hershko Unit of Biochemistry, The B. Rappaport Faculty of Medi-
v
vi • Contributors
cine and The Rappaport Institute for Research in the Medical Sciences,
Technion-Israel Institute of Technology, Haifa 31096, Israel
Mark Hochstrasser Department of Biochemistry and Molecular Biology,
University of Chicago, Chicago, Illinois 60637
Peter M. Howley Department of Pathology, Harvard Medical School, Bos-
ton, Massachusetts 02115
Jon M. Huibregtse Department of Molecular Biology and Biochemistry,
Rutgers University, Piscataway, New Jersey 08855
Stefan Jentsch Zentrum flir Molekulare Biologie der Universitat,
Heidelberg, D-69120 Heidelberg, Germany
E. S. Johnson The Rockefeller University, New York, New York 10021-6399
N. Johnsson Max-Delbriick-Laboratorium, D-50829 Cologne, Germany
J. A. Johnston Division of Biology, California Institute of Technology,
Pasadena, California 91125
Randall W. King Department of Cell Biology, Harvard Medical School,
Boston, Massachusetts 02115
Ron R. Kopito Department of Biological Sciences, Stanford University,
Stanford, California 94305-5020
Daniel Kornitzer Department of Molecular Microbiology, The B. Rappaport
Faculty of Medicine, Technion-Israel Institute of Technology, Haifa 31096,
Israel
Y. T. K won Division of Biology, California Institute of Technology, Pas-
adena, California 91125
Michael Landon Department of Biochemistry, University of Nottingham
Medical School, Queen's Medical Centre, Nottingham NG7 2UH, United
Kingdom
F. Levy Ludwig Institute for Cancer Research, CH-1066 Epalinges, Switzer-
land
O. Lomovskaya Microcide, Inc., Mountain View, California 94043
James Lowe Department of Clinical Laboratory Sciences, University of
Nottingham Medical School, Queen's Medical Centre, Nottingham NG7
2UH, United Kingdom
Andrei Lupas Molekulare Strukturbiologie, Max-Planck-Institute fiir Bio-
chemie, D-82152 Martinsried, Germany
K. Madura Department of Biochemistry, UMDNJ-Johnson Medical
School, Piscataway, New Jersey 08854
Carl G. Maki Department of Pathology, Harvard Medical School, Boston,
Massachusetts 02115
Tom Maniatis Department of Molecular and Cellular Biology, Harvard Uni-
versity, Cambridge, Massachusetts 02138
R. John Mayer Department of Biochemistry, University of Nottingham
Medical School, Queen's Medical Centre, Nottingham NG7 2UH, United
Kingdom
•
Contributors vii
I.Ota Department of Chemistry and Biochemistry, University of Colorado,
Boulder, Colorado 80309-0215
Jan-Michael Peters Department of Cell Biology, Harvard Medical School,
Boston, Massachusetts 02115; present address: Research Institute of Molecu
lar Pathology, A-l030 Vienna, Austria
Cecile M. Pickart Department of Biochemistry, Johns Hopkins University,
Baltimore, Maryland 21205
Martin Rechsteiner Department of Biochemistry, University of Utah School
of Medicine, Salt Lake City, Utah 84132
T. Riimenapf Institut fUr Virologie, Fachbereich Veterinarmedizin, 35392
Giessen, Germany
Martin Scheffner Deutsches Krebsforschungszentrum, Angewandte Tumor-
virologie, D-69120 Heidelberg, Germany
T. E. Shrader Department of Biochemistry, Albert Einstein College of Medi-
cine, Bronx, New York 10461
Susan Smith Zentrum fUr Molekulare Biologie der Universitat Heidelberg,
69120 Heidelberg, Germany; present address: Mitotix, Inc. Cambridge, Mas
sachusetts 02139
T. Suzuki Division of Biology, California Institute of Technology, Pasadena,
California 91125
G. Thrner Division of Biology, California Institute of Technology, Pasadena,
California 91125
A. Varshavsky Division of Biology, California Institute of Technology, Pas-
adena, California 91125
P. R. H. Waller Testa, Hurwitz & Thibeault, Boston, Massachusetts 02110
A. Webster Division of Biology, California Institute of Technology, Pasa
dena, California 91125
Keith D. Wilkinson Department of Biochemistry, Emory University, At-
lanta, Georgia 30083
Y. Xie Division of Biology, California Institute of Technology, Pasadena,
California 91125
Preface
The last several years have been a landmark period in the ubiquitin field. The
breadth of ubiquitin's roles in cell biology was first sketched, and the importance
of ubiquitin-dependent proteolysis as a regulatory mechanism gained general
acceptance. The many strands of work that led to this new perception are re
counted in this book. A consequence of this progress is that the field has grown
dramatically since the first book on ubiquitin was published almost a decade ago
[M. Rechsteiner (ed.), Ubiquitin, Plenum Press, 1988]. In this span, students of the
cell cycle, transcription, signal transduction, protein sorting, neuropathology,
cancer, virology, and immunology have attempted to chart the role of ubi quit in in
their particular experimental systems, and this integration of the field into cell
biology as a whole continues at a remarkable pace. We hope that for active
researchers in the field as well as for newcomers and those on the fence, this book
will prove helpful for its breadth, historical perspective, and practical tips.
Structural data are now available on many of the components of the ubiquitin
pathway. The structures have provided basic insights into the unusual biochemical
mechanisms of ubiquitination and proteasome-mediated proteolysis. Because
high-speed computer graphics can convey structures more effectively than print
media, we have supplemented the figures of the book with a Worldwide Web site
that can display the structures in a flexible, viewer-controlled format. For many of
the chapters, a visit to this Web site will help to substantiate and reinforce points
drawn in the text, and allow each individual to get to know those aspects of each
structure that are of most interest to that person. The site will be updated as
additional structures are solved.
This book was made possible by the enthusiasm of almost 50 authors who
generously devoted their time to the preparation of the various chapters, and many
others have contributed by providing unpublished observations and helpful com
ments. Our thanks to all of them. We are especially grateful to Joanna Lawrence at
ix
x • Preface
Plenum Press in London, who has guided the production of this book and the
accompanying Worldwide Web site, and to Markus Rohrwild and Bob Freeman at
Harvard Medical School in Boston, who assembled this site.
You can visit our associated Web sites for the latest protein structures of the
ubiquitin system:
http://cbweb.med.harvard.edu/ubiquitinl
http://www.at.embnet.org/mirror/ubiquitinl
lan-Michael Peters
Vienna, Austria
I. Robin Harris
Mainz, Germany
Daniel Finley
Boston, Massachusetts
Contents
Chapter 1
The Ubiquitin System: Past, Present, and Future Perspectives
i\vrann lIershJco
1. Introduction ............................................ .
2. Discovery of the Role of Ubiquitin in Protein Breakdown ........ 2
3. Identification of the Enzynnatic Reactions of the Ubiquitin Pathway 3
4. Current State of Knowledge on Mechanisnns and Functions
of the Ubiquitin Systenn . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
4.1. Enzynne Connponents ................................. 5
4.2. Sonne Cellular Proteins Degraded by the Ubiquitin Systenn .. 7
5. Challenges for the Future .................................. 11
6. Concluding Rennarks ...................................... 13
7. References ............................................... 13
Chapter 2
Polyubiquitin Chains
Cecile M. Pickart
1. Introduction ............................................. 19
2. Ubiquitin................................................ 20
2.1. Ubiquitin Conservation and Structure . . . . . . . . . . . . . . . . . . . . 20
2.2. Ubiquitin Genes ..................................... 22
2.3. Ubiquitin-Re1ated GeneslProteins ....................... 23
2.4. Ubiquitin Mutants ................................... 30
xi
