Progress in Cell Cycle Research

244 Pages·2000·16.753 MB·English

by  Mark E. Ewen (auth.), Laurent Meijer, Armelle Jézéquel, Bernard Ducommun (eds.)

Progress in
Cell Cycle Research
Volume 4
A Continuation Order Plan is available for this series. A continuation order will bring delivery of each new volume
immediately upon publication. Volumes are billed only upon actual shipment. For further information please contact
the publisher.
Progress in
Cell Cycle Research
Volume 4
Edited by
Laurent Meijer
Armelle Jezequel
Centre National de la Recherche Scientifique
Roscoff, France
and
Bernard Ducommun
Universite Paul Sabotier
Centre National de la Recherche Scientifique
Toulouse, France
SPRINGER SCIENCE+BUSINESS MEDIA, LLC
Front cover. PTK1 cells after cytokinesis (micrograph courtesy of Dr. Conly L. Rieder)
ISSN 1087-2957
ISBN 978-1-4613-6909-7 ISBN 978-1-4615-4253-7 (eBook)
DOI 10.1007/978-1-4615-4253-7
© 2000 Springer Science+Business Media New York
Originally published by Kluwer Academic / Plenum Publishers in 2000
Softcover reprint of the hardcover 1st edition 2000
http://www.wkap.nl/
10 9 8 7 6 5 4 3 21
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
Preface
The "Progress in Cell Cycle Research" series is dedicated to serve as a collection of reviews on various
aspects of the cell division cycle, with special emphasis on less studied aspects. We hope this series will
continue to be helpful to students, graduates and researchers interested in the cell cycle area and related fields.
We hope that reading of these chapters will constitute a "point of entry" into specific aspects of this vast and
fast moving field of research. As PCCR4 is being printed several other books on the cell cycle have appeared
(ref. 1-3) which should complement our series.
This fourth volume of PCCR starts with a review on RAS pathways and how they impinge on the cell cycle
(chapter 1). In chapter 2, an overview is presented on the links between cell anchorage -cytoskeleton and cell
cycle progression. A model of the Gl control in mammalian cells is provided in chapter 3. The role of histone
acetylation and cell cycle contriol is described in chapter 4. Then follow a few reviews dedicated to specific cell
cycle regulators: the 14-3-3 protein (chapter 5), the cdc7/Dbf4 protein kinase (chapter 6), the two products of the
pI6/CDKN2A locus and their link with Rb and p53 (chapter 7), the Ph085 cyclin-dependent kinases in yeast
(chapter 9), the cdc25 phophatase (chapter 10), RCCI and ran (chapter 13). The intriguing phosphorylation
dependent prolyl-isomerization process and its function in cell cycle regulation are reviewed in chapter 8. Our
current knowledge of the molecular mechanisms of cell cycle regulation has greatly benefited from the use of
oocyte maturation, a unique but diverse cellular process investigated in a large variety of models reviewed in
chapter 11. The cross-talks between MAP kinase and cdc2/ cyclin B in oocytes have been particularly well
understood in Xenopus (Chapter 12). More and more data show the interference of viral proteins with the
mammalian cell cycle (see review in chapter 1 of PCCR3 I). One such example, the HfLV-I tax protein, is
described in chapter 14. Our knowledge of the cell cycle is spreading to protozoan parasites, as nicely reviewed
in chapter 15, and this may have great therapeutical consequences. Quite fascinatingly, the cell cycle is
regulated by the circadian rhythm, from unicellular organisms (chapter 16) to man (chapter 17). The use of cell
cycle specific treatments in cancer therapy may greatly benefit from understanding and use of the links between
the cycle and the rhythm. Major advances have been recently made in the identification of the molecular actors
regulating the circadian rhythm. We anticipate that some cell cycle and circadian rhythm regulators will soon
be found to be connected! The treatment of cancer (and other cell cycle related diseases) will also obviously
benefit from a better understanding of the connections between cell cycle and apoptosis (chapter 18). As more
and more "cell cycle drugs" are being discovered, their use as anticancer drugs is being extensively
investigated; they are reviewed in chapter 19. The discovery of cell cycle regulators in the brain of Alzheimer's
disease patients, leaves us with the idea that cell cycle studies, initially supported by the antitumour purpose,
may have applications in quite unexpected fields.
We are particularly grateful to the contributors of PCCR4 who have accepted to spend a bit of their time
away from the bench and their mainstream articles to write a review on their field of interest. We also thank the
members of the Roscoff Cell Cycle Group for help and support and acknowledge the efficiency of the editorial
staff at Plenum Press. The support of the C.N.RS. ("Centre National de la Recherche Scientifique") and the
"Conseil Regional de Bretagne" is also to be acknowledged.
Roscoff, Bretagne, France
Laurent MEIJER
Armelle JEZEQUEL
Bernard DUCOMMUN
1. Ruffolo, RR, Poste, G. & Metcalf, B.W. (editors), (1997). Cel cycle regulation. Harwood Academic Publishers,
174pp.
2. Francis, D., Dudits, D. & fuze, D. (editors) (1998). Plant Cell Division. Portland Press, London & Miami,
Research Monograph X, 347 pp.
3. Stein, G.S., Baserga, R., Giordano, A. and Denhardt, D.T. (editors), (1999) The molecular basis of cell cycle and
growth control. Wiley-Liss, New York, 389 pp.
v
Contents
Relationship between RAS pathways and cell cycle control
Mlrk E. Ewen
1
Cell-anchorage, cell cytoskeleton, and Rho-GTPase family in regulation of cell cycle progression
Ichiro Tatsuno, Aizan Hirai, and Yaushi Saito
19
The Continuum model and G1-control of the mammalian cell cycle
Stephen Cooper
27
Histone acetylation and the control of the cell cycle
Laura Magnaghi-Jaulin, Slimane Ait-Si-Ali, and Annick Harel-Bellan
41
14-3-3 proteins and growth control
Wronique Baldin
49
A Cdc7p-Dbf4 protein kinase activity is conserved from yeast to humans
Leland H. Johnston, Hisao MJisai, and Akio Sugino
61
Alternative product of the pl6/CKDN2A locus connects the Rb and p53 tumor suppressors
Marion C. James, and Gordon Peters
71
Phosphorylation-dependent prolyl isomerization: a novel cell cycle regulatory mechanism
KunPing Lu
83
Functions of Pho85 cyclin-dependent kinases in budding yeast
Jason Moffat, Dongqing Huang, and Brenda Andrews
97
Cell cycle regulation by the Cdc25 phosphatase family
Ida Nilsson, and Ingrid Hoffmann
107
Molecular mechanisms of the initiation of oocyte maturation: general and species-specific aspects
Mlsakane Yamashita, Koichi Mita, Noriyuki Yoshida, and Tomoko Kondo
115
The activation of MAP kinase and p34cdc2/cyclin B during the meiotic maturation of Xenopus oocytes
Amparo Palmer and Angel R. Nel:treda
131
Premature chromatin condensation caused by loss of RCa
Hitoshi Nishijima, Takashi Seki, Hideo Nishitani, and Takeharu Nishimoto
145
HTL V- I tax and cell cycle progression
Christine Neuveut, and Kuan-Teh Jeang
157
The cell cycle in protozoan parasites
Christian Doerig, Debopam Chakrabarti, Barbara Kappes, and Keith Matthews
163
Circadian control of cell division in unicellular organisms
Tetsuya Mori, and Carl H. Johnson
185
Circadian variation of cell proliferation and cell cycle protein expression in man: clinical implications
Georg Bjarnason, and Richard Jordan
193
VII
Molecular switches that govern the balance between proliferation and apoptosis
Bert Schutte, and Frans C.S. Ramaekers
207
Molecular events that regulate cell proliferation: an approach for the development of new anticancer drugs
Eve Damiens
219
Abortive oncogeny and cell cycle-mediated events in Alzheimer disease
Arun K. Raina, Xiongwei Zhu, Mervyn Monteiro, Atsushi Takeda, and Mark A. Smith
235
Contributors
243
Index
245
VIII
Progress in Cell Cycle Research, Vol. 4, 1-17, (2000)
(Meijer, L., Jezequel, A., and Ducommun, B., eds.) Kluwer Academic /Plenum Publishers, New York
chapter 1
Relationship between Ras pathways and cell cycle control
MarkE.Ewen
Dana-Farber Cancer Institute, Harvard Medical School
44 Binney Street, Boston, MA 02115, USA.
The ordered execution of the two main events of cellular reproduction, duplication of the genome and
cell division, characterize progression through the cell cycle. Cultured cells can be switched between cycling
and non-cycling states by alteration of extracellular conditions and the notion that a critical cellular control
mechanism presides on this decision, whose temporal loCation is known as the restriction point, has become
the focus for the study of how extracellular mitogenic signalling impinges upon the cell cycle to influence
proliferation. This review attempts to cover the disparate pathways of Ras-mediated mitogenic signal
transduction that impact upon restriction point control.
MITOGENIC SIGNALLING AND THE Gl cells it must not only duplicate its genetic material
PHASE OF THE CELL CYCLE but must also double its total biomass. This simple
analysis suggests there exists some measure of co
The ordered execution of the two main events of
ordination between control of both the chromosomal
cellular reproduction, duplication of the genome and
(DNA) cycle and cellular protein biosynthesis. In
cell division, characterize progression through the
support of this notion, cells treated in Gl prior to the
mammalian cell cycle. These two readily discernible
R point with doses of cycloheximide sufficient to
processes, DNA synthesis (S phase) and mitosis (M
cause a moderate inhibition of protein synthesis also
phase), and the "gaps" between them, G1 (before S)
arrest with a G1 DNA content, while those treated
and G2 (before M) thus provide an operational
after R, or in S, G2 or M continue to execute the cell
subdivision of the cell cycle into four discrete phases.
cycle program to become arrested in the following
Cells can exist in an alternative "out of cycle" state (of
G1(4, 7-9). Indeed, Pardee's original definition of the
minimal metabolism) known as quiescence
R point was made upon sensitivity to cycloheximide
(designated GO), and the rate of proliferation in a
as well as dependency on serum factors.
given population (of cells) is largely determined by
the relative proportions of cycling versus quiescent Taken together, these observations indicate that
cells. both sufficient biosynthetic capacity and appropriate
extracellular signals are required for passage through
Cells in culture can be switched between
the R point and initiation of a new round of cellular
proliferative (cycling) and quiescent (non-cycling)
replication. The bigger question of whether
states by alteration of extracellular conditions (e.g.
mitogenic signalling pathways impacts simulta
nutrient availability, mitogen concentration) and the
neously yet independently upon the processes of
notion that a critical cellular control mechanism
biosynthesis and the chromosome cycle, or whether
presides over this decision, whose temporal location
the stimulation of one results in the co-ordinate
is known as the restriction point, has become the
regulation of the other (as a fait a compli) remains to
focus for the study of how extracellular mitogenic
be answered. In any case, what is clear is that R is a
signalling impinges upon the cell cycle to influence
common point of convergence. In the following
proliferation.
pages, I will attempt to review the disparate
Quiescent cells have a 2N DNA content, the same pathways of Ras-mediated mitogenic signal trans
as those in G1, suggesting that the switch to and from duction that impact upon restriction point control.
GO is made during this phase. Indeed, seminal
observations made nearly twenty-five years ago by THE DISCOVERY OF RAS
Pardee showed that there is a window of time in G1 Concurrent with the development of the notion of
during which serum factors are absolutely required the restriction point, a seemingly unrelated field of
for further progress into the remainder of the cycle investigation led to the discovery of a class of genes
(1). It is the point at which the cell loses its involved in cellular transformation known as
dependency upon extracellular conditions for cell oncogenes. Many of these gene products would
cycle progression that he defined as R (reviewed in eventually be shown to participate in mitogenic
(2-5) ). In murine fibroblasts R lies about two hours signalling during GO and G1.
prior to the initiation of S phase. Similar work in
chicken cells also suggested that R lies somewhere in Virology has long provided important cues in the
mid to late Gl(6). Additionally, it is self evident that study of mammalian cells. It was an understanding
of the transforming potential of RNA tumor viruses
before a cell can divide to produce two daughter
1
M.E.EWEN
(in particular retroviruses) at the molecular level that (proto-oncogene), is due to a single point mutation in
paved the way to the discovery of oncogenes. Work its coding sequence (27-29). Similarly, retroviruses
some thirty years ago on an avian RNA virus called harbouring the ras oncogene also encode a mutant
Rous sarcoma virus (10) provided an understanding oncogenic form of the protein. Since the discovery of
of how a virally encoded "transforming potential" ras over 30 oncogenes have been identified, of which,
could be propagated genetically (11-13). Further ras is the most frequently mutated in human cancer
more, these investigations provided the molecular (30).
tools to ask about the nature of this "transforming
LINKING RAS TO Gl PROGRESSION
potential".
AND RESTRICTION POINT CONTROL
A key to the answer was the observation that the
Ras biochemistry: active and inactive forms
transforming avian sarcoma viruses contained more
The manner of its discovery-as an oncogene that
genetic information than their nontransforming
provides a selective advantage to tumor cells:
counterparts. Both types of viruses were equally
suggested that Ras might have some role ~
competent in their ability to infect cells and replicate
proliferation or growth control. Though this
and it was therefore assumed that the additional
assumption is for the most part correct, it is rather
genetic information carried by the transforming
naive given what we now know of other cellular
viruses was not involved in viral replication per se
processes, principally cell adhesion and cell death
but rather in providing the virus with a selective
mechanisms, whose derangement's provide tumor
growth advantage. Utilising both strains of Rous
cells with a growth advantage. Keys to
sarcoma virus, Bishop, Varmus and co-workers
understanding the cellular functions of Ras were the
isolated the extra genetic material carried by the
discoveries that this 21 kilodalton protein possesses
transforming virus, which they termed cDNA sarc
guanine nucleotide binding activity and has intrinsic
for cDNA-bearing sarcoma producing gene
GTPase activity (31-33). Oncogenic mutants of Ras
sequences, now commonly referred to as v-Src, as the
were shown to either exhibit decreased GTPase
first, and prototypic, oncogene (14).
activity or to increase the rate of exchange of bound
Surprisingly, when the v-Src cDNA was used as a GDP for free GTP. Within the cell the concentration
probe, it was found to be present in the genomes of of GTP is ten times that of GDP. It was thus correctly
nontransformed avian cells (15) as well as in cells assumed that GTP-bound Ras was the active form
from several other species, including humans. The and the GDP-bound form was inactive.
significance of this observation was that it would
Linking Ras to the action of growth factor and
subsequently become clear that cellular genes, with
cytokine receptors
normal functions, comprised the transforming
It was found that oncogenic and wild type Ras
potential of many retroviruses. Using a similar
were post-translationally modified via covalent
methodology, Scolnick and colleagues isolated the
attachment of lipid which anchored the protein to
ras (from rat sarcoma) genes, Ha-ras and Ki-ras (16),
the inner plasma membrane (34-36) . This placed Ras
as the transforming genes of the Harvey and Kirsten
in the proximity of membrane receptors involved in
strains of rat sarcoma viruses (17, 18), respectively.
extracellular signalling. The importance of these
Both of these viral genes were also shown to be
observations came to light in 1990 when the first
present in the genomes of several species including
humans (19). Later a distinction was made, and the physiological stimulus controlling Ras activation was
identified. Activation of the T cell receptor (TCR) or
normal cellular homologues of viral oncogenes were
referred to as proto-oncogenes. the interleukin 2 receptor causes a rapid stimulation
of Ras, as measured by the ratio of GTP- to GDP
In the early 80s ras genes were discovered by a
bound forms of the protein coincident with the
completely independent route. Several laboratories
induction of cell proliferation (37). TCR initiates the
had shown that DNA fragments from animal and
GOjGl transition and interleukin 2 receptor the
human tumors or chemically transformed cells could
GljS transition, suggesting that Ras regulates
transform the "normal" mouse NIH 3T3 fibroblasts
progression through Gl via multiple receptors.
line (20-22). Such experiments were motivated by
Similar observations were made in murine
studies on bacterial virulence performed four
fibroblasts with respect to the effects of PDGF, EGF
decades earlier by Avery that led to the seminal
and insulin in promoting progression from GO to Gl
demonstration that DNA was the genetic material
and Gl to S phase (9, 38). Various growth factors
(23).
have been defined by virtue of their ability to
In this way, the laboratories of Weinberg, Cooper facilitate the GOjGl transition, initiated a process
and Wigler identified ras as one of the genes isolated called competence, and the GljS transition,
from human cancer lines capable of transforming involving progression through the restriction point
rodent cells in culture (24-26). The ability of ras to (3). We now know that activation of several growth
cause oncogenic transformation, in contrast to its factor and cytokine receptors stimulate the activity of
non-transforming wild type cellular homologue Ras. Together, these studies circumstantially
2
CHAPTER 1/ RAS AND TIlE CELL CYCLE
receptor tyrosine kinase
cell membrane
• COP-bound inactive Ras
I fa~r-mediatecl
growth
• receptor activation
receptor phosphorylati(ln
and activation
CIT-bound active Ras
SH2-mediated
interaction
SI-I3-mediated
interaction
Figure 1. Growth factor stimulation leads to receptor tyrosine kinase activation and autoph08phorylation. Phosphorylation of the
receptor provides a docking site for cytosolic Grb2-Sos complexes, resulting in the recruitment of this complex to the plasma membrane,
where Ras is anchored. Recruitment of Sos to the membrane allows it to promote the exchange of GOP for GIT on Ras, resulting in its
activation.
link the action of extracellular factors that influence function of the particular cell type used.
the progression from GO to S phase, various Alternatively, they can be explained by differing
membrane receptors, and the activation of Ras. degrees of the absolute amount of activated Ras
achieved in each experimental system, although
Ras and the cell cycle
these irregularities may equally reflect additional
More direct experiments addressed the
complexities.
importance of Ras in cell cycle control.
Microinjection of activated or wild type Ras was
UPSTREAM AND DOWNSTREAM OF RAS
found to induce DNA synthesis from quiescence (39,
40), suggesting that Ras is sufficient for progreSSion Ras functions ultimately as a signal transducer. In
from GO to S phase. In addition, experiments order to understand how Ras affects cell cycle
involving microinjection of a Ras neutralising progression it is therefore important to know how
antibody or expression of a dominant-negative Ras is activated, and once active, how it transmits
mutant of Ras have demonstrated that Ras is signals. Below I summarise how receptor activation
required for progression from GO to a point in late leads to the stimulation of Ras activity and the
G1, roughly coinciding with the restriction point (41- downstream effector pathways in which Ras
44). signalling operates.
However, it is noteworthy that depending on the How receptor tyrosine kinases activate Ras
particular cellular system and the experimental It took nearly ten years from its discovery to
approach used, there is some variation on the results begin to elucidate how various growth factors and
described above. For example, using an inducible cytokines regulate the activity of Ras (Figure 1).
system, expression of one of the oncogenic forms of Signalling is initiated by growth factors binding to
Ras, Ras(V12), was insufficient to induce S phase their receptors, which in tum induce receptor
entry from a serum-starved state (45). Lilcewise, "add dimerization and trans tyrosine phosphorylation
back" experiments using mutant PDGF receptors (autophosphorylation). These phosphotyrosine
capable of discriminately activating various signal residues, in a particular context, are recognised by
transduction pathways suggested that activation of the adaptor molecule, Grb2, through its SID domain
Ras alone was not sufficient to induce DNA synthesis (Src homology domain 2). Grb2 associates with 50s, a
(46). These apparent discrepancies lilcely reflect the nucleotide exchange factor for Ras. The interaction
difference in the mitogenic potential of Ras as a between Grb2 and 50s is mediated via two SH3
3