CELL DIVISION AND CELLULAR COMMUNICATION

Cyclin-Dependent Kinases and Cell Division in Plants— The Nexus

Correspondence to: Dirk Inzé, diinz{at}gengenp.rug.ac.be (E-mail), 32-9-2645349 (fax)

	INTRODUCTION

TOP INTRODUCTION DIVERSITY OF CDKs AND... WHICH PLANT CDKs AND... HOW DOES CDK ACTIVITY... WHAT DO WE KNOW... FUNCTIONS? PERSPECTIVES REFERENCES

Cell division is one of the most conspicuous features of life, and thus several elements of the control of cell division are common to both prokaryotes and eukaryotes (Amon 1998 ; Leatherwood 1998 ). The degree of evolutionary conservation is especially striking among eukaryotes, where progression through the successive phases of the cell cycle (S, G2, M, and G1) in species as diverse as yeast and humans is driven by a common class of heterodimeric serine/threonine protein kinases. These kinases consist of a catalytic subunit, termed cyclin-dependent kinase (CDK), and an activating subunit, cyclin (reviewed in Nigg 1995 ).

The first indication that this commonality might extend to the plant kingdom came with the identification of a plant protein immunologically related to the CDKs (John et al. 1989 ), a finding that was followed by the cloning of a cDNA fragment encoding a CDK-like protein from pea (Feiler and Jacobs 1990 ). Subsequently, it became clear that several putative CDKs and cyclins are present in each plant species and that at least some of them are pertinent to our understanding of cell division control (Hemerly et al. 1995 ; Doerner et al. 1996 ).

Several questions nevertheless remain to be addressed. For example, which putative cyclins and CDKs are involved in cell division control in plants? What are their particular functions? How is their activity regulated? Here, we focus on molecular control of the cell cycle in higher plants and do not deal with the developmental and environmental control of cell division. For more information on these latter issues, the reader is referred elsewhere (Francis et al. 1998 ).

	DIVERSITY OF CDKs AND CYCLINS IN PLANTS

TOP INTRODUCTION DIVERSITY OF CDKs AND... WHICH PLANT CDKs AND... HOW DOES CDK ACTIVITY... WHAT DO WE KNOW... FUNCTIONS? PERSPECTIVES REFERENCES

Intensive cloning efforts over the past 7 years have identified a large number of CDK-like proteins (referred to as CDKs hereafter) in diverse plant species, among which at least five types can be distinguished on the basis of their sequences (see Segers et al. 1997 ; summarized in Table 1). The best-characterized plant CDKs belong to the A-type class. This class comprises kinases most closely related to the prototypical CDKs, yeast cdc2/CDC28 and animal CDK1 and CDK2, which share the conserved PSTAIRE motif in the cyclin binding domain. In addition to this large group of CDKs, several non-PSTAIRE CDKs have been described in plants. Some of them cannot be clearly affiliated with any other class of CDKs on the basis of sequence similarity. The situation may be even more complex in plant species that possess more than one representative of a given type of CDK, although it should be noted that not all plant species appear to possess all types of CDKs. For example, no homologs of the rice R2 kinase could be detected in Arabidopsis (Yamaguchi et al. 1998 ). Currently, only A and B classes of CDKs are well defined; other classes are represented only by one or two known members whose distribution in the plant kingdom remains unclear.

A similar situation exists with the cyclins. Numerous cDNAs encoding putative cyclins (referred to as cyclins hereafter) have been identified in a diverse range of plant species (for a compilation, see Renaudin et al. 1996 ). Arabidopsis alone possesses at least 15 cyclins. Analysis of the deduced peptide sequences in the conserved "cyclin box" has enabled the classification of these cyclins into nine groups: A1, A2, A3, B1, B2, D1, D2, D3, and D4, with the lettering scheme reflecting their similarities with the mammalian cyclins A, B, and D (Table 2; Renaudin et al. 1996 ; De Veylder et al. 1999 ). More recently, cyclins with similarity to mammalian cyclin C have been identified in rice and Arabidopsis, thus adding even greater complexity to efforts to classify plant cyclins.

The classification scheme described above, although helpful, does not necessarily reflect the functional properties of the cyclins. In particular, cyclins from groups A2, B1, D2, and D3 may comprise functionally distinct members, as judged by their subcellular localization and expression patterns (see below). In due course, the completion of the Arabidopsis genome sequencing project will provide definitive answers to questions regarding the profusion and diversity of plant CDKs and cyclins.

	WHICH PLANT CDKs AND CYCLINS ARE AT WORK IN THE CELL CYCLE?

TOP INTRODUCTION DIVERSITY OF CDKs AND... WHICH PLANT CDKs AND... HOW DOES CDK ACTIVITY... WHAT DO WE KNOW... FUNCTIONS? PERSPECTIVES REFERENCES

Lately, it has become increasingly clear that certain CDKs and cyclins in yeast and animals have nothing to do with cell division control. Thus, the time is ripe to ask the question, which of the many identified plant CDKs and cyclins are actually involved in regulating the cell cycle? There is now an extensive, albeit mainly circumstantial, body of evidence that at least some plant CDKs and their associated proteins function in cell cycle control. One of the strongest arguments is the ability of many of these proteins to substi-tute the functions of their yeast and animal homologs (Table 1 and Table 2; Hata et al. 1991 ; Hemerly et al. 1992 ; Renaudin et al. 1994 ; Dahl et al. 1995 ; Meskiene et al. 1995 ; Setiady et al. 1995 ; Soni et al. 1995 ; Day et al. 1996 ; Ito et al. 1997 ; Sundaresan and Colasanti 1998 ). Although these data might appear to be conclusive, it should be noted that animal B and C cyclins are known to complement G1 cyclin deficiency in yeast despite the fact that there is no indication that they play a role in G1 progression (in the case of cyclin B) or any aspect of cell division (cyclin C) in animals. The consistently observed correlation between cell division and the expression patterns of many plant cyclins and CDKs is, similarly, both supportive and circumstantial.

More compelling data—accelerated progression through mitosis, including a rapid disintegration of the preprophase band (PPB), nuclear envelope breakdown, and chromosome condensation—have been obtained upon injection of active CDK complexes from metaphase plant cells into Tradescantia stamen hair cells (Hush et al. 1996 ). The composition of the complexes used in these studies, however, is unknown.

Currently, experiments in plants support relevance for cell division control only for CDC2aAt, CDC2bAt, and CYCB1;1 and by extrapolation for their orthologs from other species. Hemerly et al. 1995 have demonstrated that downregulation of CDC2aAt activity in plants is sufficient to compromise the rate of cell proliferation and other aspects of cell division, such as the orientation of cell division planes and cell size control. Because such downregulation does not affect the relative duration of G1 and G2, CDC2aAt probably functions in both the G1-to-S and G2-to-M transitions. In a similar way, we have shown that downregulation of B-type CDKs in transgenic plants lengthens the relative duration of G2, thus implicating these kinases in the progression through G2 (V. Mironov, A. Porceddu, J.-P. Reichheld, and D. Inzé, unpublished results). On the other hand, Doerner et al. 1996 have shown that cell proliferation in Arabidopsis roots can be boosted by ectopic expression of the CYCB1;1 cyclin. This work demonstrates that CYCB1;1 might be a limiting factor for cell division in Arabidopsis, although the phase of the cell cycle at which it operates was not identified (Doerner et al. 1996 ).

There is no evidence for cell cycle functions of PITAIRE or SPTAIRE CDKs. Moreover, the expression pattern of an Arabidopsis PITAIRE kinase closely related to CDC2cMs argues against the involvement of this group of CDKs in cell division control because no expression associated with actively dividing cells was detected by in situ hybridization (V. Mironov, R.M. de Pinho Barroco, and D. Inzé, unpublished results).

	HOW DOES CDK ACTIVITY CHANGE THROUGH THE CELL CYCLE?

TOP INTRODUCTION DIVERSITY OF CDKs AND... WHICH PLANT CDKs AND... HOW DOES CDK ACTIVITY... WHAT DO WE KNOW... FUNCTIONS? PERSPECTIVES REFERENCES

Routinely, CDK activity is assessed by histone H1 phosphorylation, and substantial biochemical evidence for the presence of CDK activity in diverse plant cells has been generated by using histone H1 as a substrate for CDK complexes purified by p13^suc1 and p9^CKS1Hs affinity selection (Jacobs 1995 ). However, these data are mainly inconclusive and difficult to interpret because the composition of the complexes is in the best case guesswork, given the ability of a number of distinct kinases, including A- and B-type CDKs, to bind p13^suc1 and p9^CKS1Hs. In only a few instances has CDK activity been traced down to a specific CDK or cyclin that has previously been identified by cloning. In particular, histone H1 kinase activity specifically associated with A-type CDKs has been analyzed in partially synchronized suspension cells of alfalfa (Bogre et al. 1997 ; Magyar et al. 1997 ), Arabidopsis, and tobacco (J.-P. Reichheld and D. Inzé, unpublished results). Most of these data consistently demonstrate high kinase activity in S, G2, and M phases, with a pronounced recession in G1.

By contrast, the activity of B-type kinases is prominently linked to mitosis. We have used specific antibodies against CDC2bAt to immunoprecipitate the histone H1 kinase activity associated with B-type CDKs in partially synchronized suspension cells and have found that the activity associated with CDC2bAt in Arabidopsis and the cognate protein in tobacco peak in the early M phase (J.-P. Reichheld and D. Inzé, unpublished results). Similarly, the activity of CDC2fMs sharply peaks in mitosis in partially synchronized alfalfa cells, albeit somewhat later (Magyar et al. 1997 ). The activity profiles of A- and B-type CDKs are illustrated in Figure 1.

View larger version (33K): [in this window] [in a new window]   Figure 1. Control of Cell Cycle Genes in Arabidopsis. Expression of Arabidopsis cyclins, CDKs, and CDK activities (using histone H1 as substrate) over the course of the cell cycle. The thickness of the filled areas qualitatively reflects the level of mRNA, protein, or activity, as indicated.

It is still to be seen which cyclins contribute to all of these activities. Currently, the information is limited to the demonstration that histone H1 kinase activity peaks in G2 in complexes immunoprecipitated with antibodies against the alfalfa cyclin CYCB2;2 (Magyar et al. 1997 ).

There are two indications that biochemically distinct histone H1 kinases, characterized by their inability to bind to an affinity p13^suc1 matrix, may be activated during DNA replication in plant cells. Indeed, a histone H1 kinase isolated from endoreduplicating maize endosperm cells by virtue of its binding to the human E2F and adenovirus E1A proteins (Grafi and Larkins 1995 ) proves to be almost absent from mitotically cycling endosperm cells. This kinase cross-reacts with an antibody against the A-type maize CDK CDC2aZm, but it does not bind p13^suc1. In addition, anti–human cyclin A antibodies precipitate a histone H1 kinase (of unknown identity) from alfalfa cells very early in S phase, a kinase that is also not recoverable by p13^suc1 affinity (Magyar et al. 1993 ).

No G1-specific CDK activities have been described in plants. In mammals, the G1 kinases consist of CDK4 or CDK6 associated with the D cyclins (Pines 1996a ). Biochemically, these CDKs differ considerably from the other CDKs in that they do not bind p13^suc1, and histone H1 is a very poor substrate. Instead, the retinoblastoma protein (pRB), a key regulator of the G1 transition, is the preferred substrate. The cloning of maize cDNAs coding for pRB-like proteins (reviewed in Gutierrez 1998 ) may provide the necessary tool for the detection of G1-specific CDK activities in plants.

	WHAT DO WE KNOW ABOUT THE MOLECULAR MECHANISMS OF REGULATION?

TOP INTRODUCTION DIVERSITY OF CDKs AND... WHICH PLANT CDKs AND... HOW DOES CDK ACTIVITY... WHAT DO WE KNOW... FUNCTIONS? PERSPECTIVES REFERENCES

In yeast and animals, CDK activity is regulated at several levels, including expression, differential subcellular localization, phosphorylation, proteolysis, and interaction with regulatory proteins. Below, we summarize our current knowledge of these events in plants.

Expression of CDKs and Cyclins
The expression of plant CDKs and cyclins has been studied rather extensively at the level of transcript accumulation. As a result, we know now that some plant CDKs cycle, as do many plant cyclins (Table 1 and Table 2 and Figure 1). In particular, all the B-type kinases analyzed so far accumulate transcripts preferentially either in S and G2 or in G2 and M phases (Fobert et al. 1994 , Fobert et al. 1996 ; Segers et al. 1996 ; Magyar et al. 1997 ; Umeda et al. 1999 ). In contrast, cell cycle phase–independent expression is typical of the majority of the plant A-type CDKs (Martinez et al. 1992 ; Hemerly et al. 1993 ; Magyar et al. 1993 , Magyar et al. 1997 ; Fobert et al. 1996 ; Segers et al. 1996 ; Setiady et al. 1996 ; Sauter 1997 ; Umeda et al. 1999 ).

The expression profiles of plant CDKs other than A or B type have drawn much less attention. The transcript of the rice CDK R2 is more abundant in G1 and S in partially synchronized rice suspension cells (Sauter 1997 ) but is rather constant in rice root meristems (Umeda et al. 1999 ). The expression of CDC2cMs and CDC2eMs in partially synchronized alfalfa suspension cells remains constant throughout the cell cycle (Magyar et al. 1997 ).

As it is in animals, the phase-dependent expression of A- and B-type cyclins in plants is under transcriptional control. Moreover, there seems to be a fair degree of correlation between the temporal expression pattern and the cyclin class as defined by primary structure (Table 2; Fobert et al. 1994 ; Kouchi et al. 1995 ; Meskiene et al. 1995 ; Setiady et al. 1995 ; Reichheld et al. 1996 ; Segers et al. 1996 ; Shaul et al. 1996 ; Ito et al. 1997 ; Sauter 1997 ; Lorbiecke and Sauter 1999 ). Interestingly, the cyclin CYCA2;1 from alfalfa, related to the A2 group, is nevertheless expressed uniformly throughout the cell cycle and has consequently been proposed to play a role in G1 (Meskiene et al. 1995 ). In terms of the mechanisms of the G1 phase transition in plants, it is important to find out whether functional homologs of Medsa;CYCA2;1 are present in other species.

The majority of D-type cyclins in both plants and animals manifest fairly constant expression levels throughout the cell cycle (Dahl et al. 1995 ; Soni et al. 1995 ; Doonan 1998 ). Plant D cyclins, by analogy with their animal homologs, have been proposed to control the G1 progression in response to growth factors and nutrients (Dahl et al. 1995 ; Soni et al. 1995 ). Unexpectedly, cyclins CYCD2;1 and CYCD3;1 from tobacco are found to be expressed predominantly during the G-to-M transition (Sorrell et al. 1999 ), suggesting that D-type cyclins in plants may also be involved in mitotic events.

Relatively little is known regarding the degree to which the protein levels of plant cell cycle genes follow the transcriptional patterns described above. The protein levels of A-type CDKs are rather stable throughout the cell cycle (Bogre et al. 1997 ; Magyar et al. 1997 ; Mews et al. 1997 ; J.-P. Reichheld and D. Inzé, unpublished results). The protein levels of B-type CDKs clearly peak in M phase (Magyar et al. 1997 ; Umeda et al. 1999 ; J.-P. Reichheld and D. Inzé, unpublished results).

The only relevant information regarding expression of plant cyclins is provided by Mews et al. 1997 , who used indirect immunofluorescence to localize four mitotic cyclins in the A1, B1, and B2 groups in maize root tip cells (Table 3). Because the signals obtained through immunolocalization may reflect epitope accessibility rather than actual protein levels, data of this kind should be interpreted with caution. Nevertheless, the results seem to confirm the prevalence of the cyclins in G2 and M and further suggest their persistence (with the exception of CYCB1;2) well into telophase. In this regard, it is worth noting that cyclins with specific functions in the completion of mitosis have recently been identified in yeast (Aerne et al. 1998 ).

Subcellular Localization
A steadily accumulating body of evidence points to the control of subcellular localization of a number of essential proteins, particularly CDC2, cyclin B, cyclin D, CDC25, and CDC6, as an important mechanism of cell cycle control in eukaryotes (Pines 1999 ). In plants, this aspect of regulation has been addressed only for A-type CDKs and four mitotic cyclins (Table 3). A-type CDKs, when assayed by indirect immunofluorescence, are predominantly found in the interphase and early prophase nucleus in maize, alfalfa, and Arabidopsis, and to a lesser extent in the cytoplasm (Colasanti et al. 1993 ; Mews et al. 1996 , Mews et al. 1997 ; Bogre et al. 1997 ; Stals et al. 1997 ).

During mitosis, A-type CDKs have been found in association with a number of cytoskeletal structures, such as the PPB, spindle, and phragmoplast. They also transiently interact with the chromosomes at the metaphase–anaphase transition in alfalfa (Stals et al. 1997 ) but apparently not in maize (Mews et al. 1997 ). The cytoplasmic labeling progressively declines as the cells of maize root tips exit the mitotic cycle and differentiate. However, the cognate proteins persist in the nuclei through all the developmental zones, including in differentiated cells (Mews et al. 1996 ). This observation may indicate that nuclear localization renders A-type plant CDKs less susceptible to proteolysis. However, Bogre et al. 1997 have observed that comparable amounts of A-type CDKs are present in the cytoplasmic and nuclear fractions of alfalfa cells in S phase, whereas the proteins are detectable by immunofluorescence only in the nucleus of the same cells. This observation suggests that epitope accessibility of plant CDKs may be influenced by subcellular localization.

The pioneering work of Mews et al. 1997 provides the first piece of data on the subcellular localization of plant cyclins (Table 3). All four cyclins display unique and dynamic patterns of localization, demonstrating that the functions of the numerous plant cyclins are not redundant. Particularly striking is the difference between the two B1 cyclins: whereas CYCB1;1, like CDC2Zm, is predominantly nuclear, CYCB1;2 localization closely resembles that of human cyclin B1 in that this cyclin is relocated to the nucleus in prophase and degraded in anaphase. Nuclear relocation in prophase has also been observed for CYCA1;1, which is at odds with the nuclear localization of animal cyclin A. These results clearly show that the functions of plant cyclins cannot be deduced from sequence similarity with their animal counterparts.

Formation of CDK/Cyclin Complexes
Whereas our knowledge of the expression of CDKs and cyclins in plants is already quite substantial, disappointingly little functional data exist regarding the CDK/cyclin complexes. First of all, we do not know whether plant CDKs are dependent on cyclins. Computer-assisted modeling of the three-dimensional structure of CDC2aAt (R. Abagyan, unpublished data) based on coordinates of the human CDK2 model (De Bondt et al. 1993 ) suggests that the plant kinase should be as cyclin dependent as the human enzyme. The only supporting experimental evidence, however, is circumstantial: on the one hand, Bogre et al. 1997 found that protein fractions from alfalfa extracts corresponding to monomeric CDKs are essentially devoid of kinase activity, as measured by histone H1 phosphorylation; on the other hand, alfalfa protein complexes immunoprecipitated with antibodies against the human cyclin A or alfalfa cyclin CYCB2;2 exhibit appropriate histone H1 kinase activity (Magyar et al. 1993 , Magyar et al. 1997 ).

Not a single active CDK/cyclin complex has been reliably identified in plants. The results of immunolocalization of CDC2Zm and mitotic cyclins in maize suggest several possible combinations (see Table 3), but these data fall short of proof. Two approaches pursued recently in our labora-tory are beginning to shed light on the CDK/cyclin complexes of Arabidopsis. First, we have identified a number of proteins capable of interacting with CDC2aAt by using the two-hybrid system, including CYCD1;1 (De Veylder et al. 1997a ) and CYCD4;1 (De Veylder et al. 1999 ). Nevertheless, it still has to be proven that such CDC2aAt/CYCD complexes are actually formed and active in plant cells. Indeed, some of the complexes formed by animal CDKs and cyclins, in particular complexes of cyclin D with CDK2 and CDK5, are known to be inactive (Ewen et al. 1993 ; Xiong et al. 1997 ).

Second, a procedure has been developed in our laboratory to purify active kinase complexes from Arabidopsis cells that contain selectively either CDC2aAt or CDC2bAt, whereby CYCB1;1 and CYCB2;2 were found to copurify preferentially with CDC2bAt and CDC2aAt, respectively (H. Stals and P. Casteels, unpublished data). Many more complexes will soon be characterized, but given the plethora of cyclins in plants, it may take some time to achieve a comprehensive overview of the system. The persistence of "orphan" cyclins in the more thoroughly characterized mammalian systems would seem to substantiate this caveat (Pines 1996a ).

Interaction with Other Cell Cycle Regulators
Several noncyclin proteins have been found in complexes with CDKs. In particular, the family of evolutionarily conserved CKS proteins (for cyclin-dependent kinase subunit) is required for progression through the cell cycle in yeast and vertebrates, although the molecular mechanisms by which these proteins act remain elusive. Crystallographic and biochemical analyses suggest that CKS proteins act as docking factors for positive and negative regulators of CDKs (Pines 1996b ).

A plant CKS homolog, CKS1At, has been isolated through the use of a two-hybrid system using CDC2aAt as bait (De Veylder et al. 1997b ). The CKS1At gene is functional in yeast, and its gene product associates with both A- and B-type Arabidopsis CDKs in vivo (in yeast) and in vitro. In situ hybridization analysis (Jacqmard et al. 1999 ) further reveals that CKS1At, together with CDC2aAt and CDC2bAt, is strongly transcribed in actively dividing tissues, suggesting that these proteins may also interact in plants. The presence of CKS1At expression in a number of polyploid tissues where CDC2aAt and CDC2bAt transcripts are present at very low levels or are absent (Jacqmard et al. 1999 ) indicates that CKS1At may play a role in the endocycle. It is conceivable that CKS1At is required for the functioning of a yet to be identified CDK of Arabidopsis, presumably one that is involved in the process of endoreduplication.

Much attention has been focused of late on a group of proteins in yeast and animals known as CDK inhibitors (CKIs). These proteins inhibit cell cycle progression through their association with CDK complexes (Nakayama and Nakayama 1998 ). A first plant gene (ICK1) with limited sequence similarity to mammalian CKIs was isolated by using a two-hybrid system with the CDC2aAt protein as bait (Wang et al. 1997 ). Two additional putative plant CKIs have since been isolated in a similar way in our laboratory. Remarkably, all these proteins show only modest sequence similarity to the human p21^Waf1/Cip1 and p27^Kip1 inhibitors. This similarity is restricted to a stretch of 30 amino acids located at the C terminus, which has been found crucial for the interaction of ICK1 with CDC2aAt and also CYCD3;1 (Wang et al. 1998 ). The remainder of the plant protein sequences has no similarity to any other protein in the public databases. Despite that, the results of Wang et al. 1998 show that the region adjacent to the conserved C terminus is, as in the animal counterparts, involved in the interaction with the cyclin (CYCD3;1 in this case). Recombinant ICK1 at nanomolar concentrations inhibits 80% of the total CDK activity (measured with the histone H1 kinase assay) recovered from Arabidopsis extracts by using p13^suc1 affinity selection (Wang et al. 1997 ). The failure to inhibit CDK activity completely is most probably due to the specificity of ICK1 for A-type CDKs (L. De Veylder and D. Inzé, unpublished results). Transcriptional induction of ICK1 by abscisic acid suggests that ICK1 may mediate the cytostatic effect of abscisic acid in plants (Wang et al. 1998 ).

The in vivo function of the plant CKI-like proteins has still to be determined. The current experimental evidence indicating that CKIs may be deployed in plant cell cycle control is limited to two circumstantial observations. Grafi and Larkins 1995 have shown that cells of maize endosperm undergoing endoreduplication contain an unidentified active inhibitor of the histone H1 kinase activity of mitotically dividing endosperm cells. Bogre et al. 1997 analyzed histone H1 kinase activity of nuclear and cytoplasmic CDKs purified from synchronized alfalfa cells either by immunoprecipitation (A-type CDKs) or by p13^suc1 binding. The observed differences in the activity profiles suggest the presence of a thermolabile inhibitor, predominantly cytoplasmic, with higher affinity for nuclear S phase CDKs. Although in the absence of some essential controls this interpretation cannot be regarded as definitive, the observed phenomenon provides a promising assay for the biochemical identification of the presumed inhibitor.

CDK Phosphorylation
Considerable progress has been achieved lately in the analysis of the post-translational regulation of CDK/cyclin complexes in plants. Zhang et al. 1996 presented the first direct evidence for the phosphorylation of CDKs as a control mechanism in plants. Tobacco pith parenchyma and Nicotiana plumbaginifolia suspension-cultured cells, arrested in G2 by the absence of cytokinin, contain CDK complexes with both reduced kinase activity and high phosphotyrosine content. Resumption of the cell cycle upon addition of cytokinin, however, results in tyrosine dephosphorylation and kinase reactivation. The in vitro treatment of the complexes from cytokinin-depleted cells with the yeast cdc25 phosphatase, highly specific for the Tyr15 of CDKs, similarly leads to their dephosphorylation and activation, implicating the Tyr15 residue as the most probable target of the inhibitory phosphorylation.

Given that Tyr15 is almost universally conserved in plant CDKs, this type of phosphorylation-dependent regulation might well prove to be common in plants. Moreover, the requirement for cytokinin in N. plumbaginifolia cells can be completely alleviated by expression of the cdc25 gene from fission yeast (John 1998 ), thus suggesting the triggering of Tyr15 dephosphorylation as the only essential function of cytokinins in the plant cell cycle. The cdc25 gene has also been expressed in transgenic tobacco plants and in cultured roots of tobacco, and in both cases the cells were found to divide at a reduced size (Bell et al. 1993 ; McKibbin et al. 1998 ). This observation further supports the importance of Tyr15 phosphorylation in the timing of mitosis in plants. Tyr15 phosphorylation also has been recently implicated in water stress responses in wheat (Schuppler et al. 1998 ). The identity of the CDK(s) subjected to inhibitory phosphorylation in all these cases, however, remains unknown.

The question of the function of Tyr15 phosphorylation has been approached from a different angle by Hemerly et al. 1995 , who produced transgenic Arabidopsis and tobacco plants expressing the double T14A/Y15F mutant of CDC2aAt that is thought to be constitutively active. These plants, unlike those expressing cdc25, develop normally, except for some tendency toward a reduced apical dominance, but unfortunately they have not been analyzed cytologic-ally. These results suggest either that CDC2aAt is not a substrate of the cytokinin-mediated control of Tyr phos-phorylation or, more likely, that there are additional tar-gets, presumably partially redundant with CDC2aAt. The much sought-after enzymes responsible for the phosphometabolism of T14/ Y15 in plant CDKs are still awaiting discovery.

The majority of animal CDKs need to be phosphorylated by the so-called CDK-activating kinases (CAKs) for full activation (Harper and Elledge 1998 ). Although it is not known whether this type of phosphorylation event is necessary to activate plant CDKs, the kinase CAK1At from Arabidopsis, which is only distantly related to the animal CAKs, has been demonstrated to possess CAK activity toward human CDK2/cyclinA complexes and to complement CAK-deficient mutants in both budding and fission yeast (Umeda et al. 1998 ). Similar to the budding yeast CAK1 kinase, CAK1At is not cyclin dependent.

There is an indication that the mechanisms of CDK activation may differ between monocotyledonous and dicotyledonous species. Yamaguchi et al. 1998 have found that the rice CDK R2, 50% identical to the animal CAK kinase CDK7, complements CAK deficiency in budding (but not fission) yeast and phosphorylates in vitro the rice CDC2Os1 and the human CDK2 with specificity identical to that of the human CAK. This observation is in conflict with a previous report that R2 has no CAK activity and instead phosphorylates efficiently the C-terminal domain of the large subunit of RNA polymerase II (Umeda et al. 1998 ).

Proteolytic Degradation
In the course of the past few years, controlled proteolysis has come into prominence as one of the most essential mechanisms underlying cell cycle transitions in eukaryotes (Peters 1998 ). Very little is known about this aspect of cell cycle control in plants, primarily because the protein levels of plant cell cycle regulators have not been adequately characterized. From what is currently known, we can only surmise that certain B-type CDKs, for example, CDC2bAt, may be subject to proteolytic removal in the S and early G2 phases, given the considerable delay in the accumulation of the protein compared with the transcript (Figure 1).

Nevertheless, there is little doubt that this form of control exists in plants because (1) the ubiquitin-dependent proteolysis system is present in plant cells, and the expres-sion of some of its elements has been linked to cell proliferation (Plesse et al. 1998 ); (2) plant A- and B-type cyclins feature the so-called destruction box, a hallmark of ubiquitin-mediated degradation, which has now been found sufficient for cell cycle–dependent protein instability in tobacco suspension–cultured cells (Genschik et al. 1998 ); and (3) PEST sequences, rich in proline (P), glutamate (E), serine (S), and threonine (T), are also portents of pro-tein degradation and are found in both plant CDKs and cyclins.

In animals and yeast, two multisubunit E3 ubiquitin ligases, SCF and APC, have been found essential for the degradation of a number of cell cycle proteins, including cyclins and CKIs (Peters 1998 ). Although homologs of a number of eukaryotic proteins that are related in function to SCF and APC have been described in plants (Leyser et al. 1993 ; Ingram et al. 1997 ; Luo et al. 1997 ; del Pozo et al. 1998 ; Porat et al. 1998 ; Ruegger et al. 1998 ; Xie et al. 1998 ), their destructive function and role in the cell cycle remain entirely speculative. Intriguingly, two of the plant homologs, AXR1 and TIR1, are implicated in auxin responses (Leyser et al. 1993 ; Ruegger et al. 1998 ). This observation raises the attractive possibility that auxin promotes cell division by triggering degradation of CKIs. However, a word of caution is necessary here because homologs of, for instance, TIR1 are involved in a diverse range of functions not necessarily related to the cell cycle.

Although the evidence for protein degradation as a universal mechanism in cell cycle control is accumulating, differences in the mechanisms of degradation of cell cycle proteins in plants compared with other eukaryotes are also anticipated. For example, some maize cyclins that bear a destruction box have been found to be resistant to proteolysis in anaphase (Mews et al. 1997 ). This finding implies the existence of an active mechanism selectively protecting plant cyclins against proteolysis in M phase.

	FUNCTIONS?

TOP INTRODUCTION DIVERSITY OF CDKs AND... WHICH PLANT CDKs AND... HOW DOES CDK ACTIVITY... WHAT DO WE KNOW... FUNCTIONS? PERSPECTIVES REFERENCES

The question mark in the title of this section is indeed necessary. Whereas a considerable amount of data implicates plant cyclins and CDKs in cell division control (as discussed above), the links between particular proteins and specific events during the cell cycle remain elusive. The subcellular localization of CDKs and cyclins provides some hints as to their potential functions (Table 3). Complexes of A-type CDKs and B1 cyclins of the CYCB1;2 subtype, for example, are very probably responsible for PPB disintegration, given that they both associate transiently with the PPB imme-diately beforehand (Hush et al. 1996 ). These same cy-clins, but not the A-type CDKs, colocalize with the condensing chromosomes and the nuclear envelope be-fore its breakdown and thus may be involved in the two processes.

By contrast, cyclin A1, in complexes with a succession of various CDK partners, may well control microtubule dynamics, as suggested by its association with all appropriate structures throughout the cell cycle. On the basis of their spatial (A-type) or temporal (B-type) expression patterns, neither A- nor B-type CDKs qualify as potential partners of cyclin A1 during the early interphase. This conclusion further invokes the presence of additional types of CDKs in the control of the plant cell cycle. Finally, A-type CDKs in complexes with cyclins B1 (CYCB1;1 subtype) and B2 are expected to phosphorylate nuclear proteins.

Growing evidence suggests that pRB-like proteins in plants might be among nuclear targets of plant CDKs. The pRB is central to the regulation of the G1-to-S transition in mammals. Phosphorylation of pRB by cyclin D- and cyclin E-dependent kinases renders it inactive as a repressor of the S phase and thereby promotes DNA replication (Mittnacht 1998 ). Significantly, the pRB binding motif LXCXE (where X denotes any amino acid) is found in all known plant D cyclins. Moreover, LXCXE-dependent interactions between D cyclins from Arabidopsis and maize pRB proteins have been demonstrated in vitro and in a yeast two-hybrid assay (Ach et al. 1997 ; Huntley et al. 1998 ). The maize pRB proteins contain multiple putative CDK phosphorylation sites, and ZmRB-1 is efficiently phosphorylated in vitro by mammalian G1- and S-specific CDKs (Huntley et al. 1998 ). Moreover, maize pRB proteins are known to undergo changes in phosphorylation during the transition to endoreduplication in the endosperm (Grafi et al. 1996 ); however, phosphorylation by plant CDKs remains to be demonstrated.

Further evidence in support of a functional role for pRB proteins in plants comes from experiments showing that the overproduction of a maize pRB-like protein inhibits geminivirus replication. This suggests that pRB-like proteins in plants may also act as negative regulators of DNA synthesis (Xie et al. 1996 ). The observation that a pRB protein in maize leaves is highly produced in differentiating but not in proliferating cells (Huntley et al. 1998 ) suggests that some plant pRB-like proteins may be involved in the suppression of cell division during differentiation.

In mammals, hyperphosphorylated pRB disengages from inhibitory complexes with proteins such as E2F and MCM7 that are involved in the activation of S phase–specific transcription (Helin 1998 ) and initiation of DNA replication (Leatherwood 1998 ). In this regard, the PROLIFERA gene, which is required for megagametophyte and embryo development in Arabidopsis, encodes a protein that is 50% identical to the mammalian MCM7 proteins (Springer et al. 1995 ); it will thus be important to see whether PROLIFERA interacts with pRB proteins in plants.

Similarly, a putative homolog of mammalian E2Fs has recently been identified in wheat (Gutierrez 1998 ), and there is an indication that, as is the case in animals, an E2F-like protein might also be a substrate for S phase–specific CDKs in maize endosperm (Grafi and Larkins 1995 ). These observations, again circumstantial, imply that the control of the S phase in plants is more similar to that occurring in animal cells than in yeast cells.

	PERSPECTIVES

TOP INTRODUCTION DIVERSITY OF CDKs AND... WHICH PLANT CDKs AND... HOW DOES CDK ACTIVITY... WHAT DO WE KNOW... FUNCTIONS? PERSPECTIVES REFERENCES

Our understanding of the basic mechanisms that regulate cell division in plants has advanced considerably in recent years. Numerous key players have been identified, and an emerging model that integrates current knowledge is shown in Figure 2. Although initial investigations of the plant cell cycle appeared to be merely confirmatory, the field is now approaching a degree of maturity such that questions specific to plants may be addressed. Given the considerable differences between plants and animals in life strategies, we can expect numerous exciting breakthroughs in the near future. Further progress will depend on gaining a better understanding of the specific roles of the CDK/cyclin complexes. We need to find out which CDK/cyclin combinations are active over the course of the cell cycle and what their targets are. Furthermore, insights into the mechanisms of activation/deactivation should be gained and upstream regulators identified.

View larger version (41K): [in this window] [in a new window]   Figure 2. Model of Cell Cycle Control in Plants. In consideration of the available data on plant cell cycle proteins and genes and in light of data on the corresponding gene products from heterologous systems, a model for cell cycle regulation in plants is proposed. Upon mitogenic stimulation (top right), D-type cyclins (CycD) are produced and associate with the A-type CDKs (A-CDKs). The resulting A-type CDK /cyclin D complexes phosphorylate a retinoblastoma-like protein (pRb), resulting in the release of pRB-interacting proteins (RIP) that in turn trigger the onset of S phase. The presence of PEST degradation sequences accounts for the short life span of the D-type cyclins. During the S phase, A-type cyclins (CycA) are synthesized to activate A-CDKs. As cells reach the end of the S phase, CDK activity is inhibited by Tyr phosphorylation. At G2, B-type cyclins appear. Because both A-type CDKs and B-type CDKs (B-CDK) display kinase activity at the G2/M transition point, both types of CDKs might coincidentally be present to associate with B-type cyclins. The correct functioning and activation of the mitotic CDKs require association with CKS1 docking factors (Cks1) and removal of the inhibitory phosphate group. The latter process was demonstrated to be cytokinin dependent. Specific degradation motifs in their protein sequences suggest that A- and B-type cyclins are destroyed during M phase, as indicated by colored fragments. The cell cycle could be arrested by the association of the A-type CDKs with CKIs.

These formidable tasks will require considerable efforts in biochemistry and cell biology, efforts that will certainly pay off in the long run. Indeed, a thorough understanding of the operation of the basic cell cycle machinery promises to provide the information and tools necessary to understand how intrinsic developmental programs and environmental cues impinge on cell division. Early payoffs are already emerging as links have been found between auxin signaling and genes known to be involved in cell cycle–related protein degradation (Leyser et al. 1993 ; del Pozo et al. 1998 ; Ruegger et al. 1998 ) and between the action of cytokinins and the regulation of CDK activity (Zhang et al. 1996 ). We can look forward to understanding how cell division is initiated, how endoreduplication is regulated, and how cells exit the cell cycle to differentiate.

The cell cycle toolbox will also allow us to address fundamental questions with regard to the role of cell division in plant growth and architecture. For example, is cell division informed by growth, or is cell division the driving force for growth? This hotly debated subject pursued for quite some time by plant biologists has fueled arguments denying any role for the control of cell cycle in plant development and reducing cell division to the surveillance of cell growth (Clark and Schiefelbein 1997 ).

Current research continues to fuel this debate. For example, in stressed cells of intercalary meristems of rice and of wheat leaves, modulations of the cell cycle have recently been shown to precede any detectable changes in cell growth (Lorbiecke and Sauter 1998 ; Schuppler et al. 1998 ). These findings provide additional evidence that cell growth in plants is not the only driving force for cell division. Further progress in cell cycle research holds the promise of not only bringing a deeper understanding of how, when, and why plant cells divide but also of how cell division in plants might be modulated.

	ACKNOWLEDGMENTS

We thank Mike Davey, Godelieve Gheysen, Marcelle Holsters, Isabelle Landrieu, and Jean-Philippe Reichheld for critical reading of the manuscript, Martine De Cock for help preparing it, and Karel Spruyt and Rebecca Verbanck for artwork. This work was supported by grants from the Interuniversity Poles of Attraction Program (Belgian State, Prime Minister's Office–Federal Office for Scientific, Technical and Cultural Affairs; P4/15), the European Commission BIOTECH program (Grant No. ERBBIO4-CT96-0217), and the Fund for Scientific Research (Flanders) (Grant No. G012196). L.D.V. is indebted to the Vlaams Instituut voor de Bevordering van het Wetenschappelijk–Technologisch Onderzoek in de Industrie for a predoctoral fellowship. D.I. is a Research Director of the Institut National de la Recherche Agronomique (France).

	REFERENCES

TOP INTRODUCTION DIVERSITY OF CDKs AND... WHICH PLANT CDKs AND... HOW DOES CDK ACTIVITY... WHAT DO WE KNOW... FUNCTIONS? PERSPECTIVES REFERENCES

Ach, R.A., Durfee, T., Miller, A.B., Taranto, P., Hanley-Bowdoin, L., Zambryski, P.C., and Gruissem, W. (1997) RRB1 and RRB2 encode maize retinoblastoma-related proteins that interact with a plant D-type cyclin and geminivirus replication protein. Mol. Cell. Biol. 17:5077-5086[Abstract/Free Full Text].

Aerne, B.L., Johnson, A.L., Toyn, J.H., and Johnston, L.H. (1998) Swi5 controls a novel wave of cyclin synthesis in late mitosis. Mol. Biol. Cell 9:945-956[Abstract/Free Full Text].

Amon, A. (1998) Controlling cell cycle and cell fate: Common strategies in prokaryotes and eukaryotes. Proc. Natl. Acad. Sci. USA 95:85-86[Free Full Text].

Bell, M.H., Halford, N.G., Ormrod, J.C., and Francis, D. (1993) Tobacco plants transformed with cdc25, a mitotic inducer gene from fission yeast. Plant Mol. Biol. 23:445-451[CrossRef][Web of Science][Medline].

Bögre, L., Zwerger, K., Meskiene, I., Binarova, P., Csizmadia, V., Planck, C., Wagner, E., Hirt, H., and Heberle-Bors, E. (1997) The cdc2Ms kinase is differentially regulated in the cytoplasm and in the nucleus. Plant Physiol. 113:841-852[Abstract].

Clark, S.E., and Schiefelbein, J.W. (1997) Expanding insights into the role of cell proliferation in plant development. Trends Cell Biol. 7:454-458[Medline].

Colasanti, J., Cho, S.-O., Wick, S., and Sundaresan, V. (1993) Localization of the functional p34^cdc2 homolog of maize in root tip and stomatal complex cells: Association with predicted division sites. Plant Cell 5:1101-1111[Abstract/Free Full Text].

Dahl, M., Meskiene, I., Bögre, L., Cam Ha, D.T., Swoboda, I., Hubmann, R., Hirt, H., and Heberle-Bors, E. (1995) The D-type alfalfa cyclin gene cycMs4 complements G₁ cyclin–deficient yeast and is induced in the G₁ phase of the cell cycle. Plant Cell 7:1847-1857[Abstract].

Day, I.S., Reddy, A.S.N., and Golovkin, M. (1996) Isolation of a new mitotic-like cyclin from Arabidopsis: Complementation of a yeast cyclin mutant with a plant cyclin. Plant Mol. Biol. 30:565-575[CrossRef][Web of Science][Medline].

De Bondt, H.L., Rosenblatt, J., Jancarik, J., Jones, H.D., Morgan, D.O., and Kim, S.-H. (1993) Crystal structure of cyclin-dependent kinase 2. Nature 363:595-602[CrossRef][Medline].

del Pozo, J.C., Timpte, C., Tan, S., Callis, J., and Estelle, M. (1998) The ubiquitin-related protein RUB1 and auxin response in Arabidopsis.. Science 280:1760-1763[Abstract/Free Full Text].

De Veylder, L., Segers, G., Glab, N., Van Montagu, M., and Inzé, D. (1997a) Identification of proteins interacting with the Arabidopsis Cdc2aAt protein. J. Exp. Bot. 48:2113-2114.

De Veylder, L., Segers, G., Glab, N., Casteels, P., Van Montagu, M., and Inzé, D. (1997b) The Arabidopsis Cks1At protein binds to the cyclin-dependent kinases Cdc2aAt and Cdc2bAt. FEBS Lett. 412:446-452[CrossRef][Web of Science][Medline].

De Veylder, L., de Almeida Engler, J., Burssens, S., Manevski, A., Lescure, B., Van Montagu, M., Engler, G., and Inzé, D. (1999) A new D-type cyclin of Arabidopsis thaliana expressed during lateral root primordia formation. Planta in press.

Doerner, P., Jørgensen, J.-E., You, R., Steppuhn, J., and Lamb, C. (1996) Control of root growth and development by cyclin expression. Nature 380:520-523[CrossRef][Medline].

Doonan, J.H. (1998). Cell division during floral morphogenesis in Antirrhinum majus. In Plant Cell Division, D. Francis, D. Dudits, and D. Inzé, eds (London: Portland Press), pp. 207–222.

Ewen, M.E., Sluss, H.K., Sherr, C.J., Matsushime, H., Kato, J.-y., and Livingston, D.M. (1993) Functional interactions of the retinoblastoma protein with mammalian D-type cyclins. Cell 73:487-497[CrossRef][Web of Science][Medline].

Feiler, H.S., and Jacobs, T.W. (1990) Cell division in higher plants: A cdc2 gene, its 34-kDa product, and histone H1 kinase activity in pea. Proc. Natl. Acad. Sci. USA 87:5397-5401[Abstract/Free Full Text].

Fobert, P.R., Coen, E.S., Murphy, G.J.P., and Doonan, J.H. (1994) Patterns of cell division revealed by transcriptional regulation of genes during the cell cycle in plants. EMBO J. 13:616-624[Web of Science][Medline].

Fobert, P.R., Gaudin, V., Lunness, P., Coen, E.S., and Doonan, J.H. (1996) Distinct classes of cdc2-related genes are differentially expressed during the cell division cycle in plants. Plant Cell 8:1465-1476[Abstract].

Francis, D., Dudits, D., and Inzé, D. (1998). Plant Cell Division. (London: Portland Press).

Genschik, P., Criqui, M.C., Parmentier, Y., Derevier, A., and Fleck, J. (1998) Cell cycle–dependent proteolysis in plants: Identification of the destruction box pathway and metaphase arrest produced by the protease inhibitor MG132. Plant Cell 10:2063-2075[Abstract/Free Full Text].

Grafi, G., and Larkins, B.A. (1995) Endoreduplication in maize endosperm: Involvement of M phase–promoting factor inhibition and induction of S phase–related kinases. Science 269:1262-1264[Abstract/Free Full Text].

Grafi, G., Burnett, R.J., Helentjaris, T., Larkins, B.A., DeCaprio, J.A., Sellers, W.R., and Kaelin, W.G., Jr. (1996) A maize cDNA encoding a member of the retinoblastoma protein family: Involvement in endoreduplication. Proc. Natl. Acad. Sci. USA 93:8962-8967[Abstract/Free Full Text].

Gutierrez, C. (1998) The retinoblastoma pathway in plant cell cycle and development. Curr. Opin. Plant Biol. 1:492-497[CrossRef][Web of Science][Medline].

Harper, J.W., and Elledge, S.J. (1998) The role of Cdk7 in CAK function, a retro-retrospective. Genes Dev. 12:285-289[Free Full Text].

Hata, S., Kouchi, H., Suzuka, I., and Ishii, T. (1991) Isolation and characterization of cDNA clones for plant cyclins. EMBO J. 10:2681-2688[Web of Science][Medline].

Helin, K. (1998) Regulation of cell proliferation by the E2F transcription factors. Curr. Opin. Genet. Dev. 8:28-35[CrossRef][Web of Science][Medline].

Hemerly, A., Bergounioux, C., Van Montagu, M., Inzé, D., and Ferreira, P. (1992) Genes regulating the plant cell cycle: Isolation of a mitotic-like cyclin from Arabidopsis thaliana.. Proc. Natl. Acad. Sci. USA 89:3295-3299[Abstract/Free Full Text].

Hemerly, A.S., Ferreira, P., de Almeida Engler, J., Van Montagu, M., Engler, G., and Inzé, D. (1993) cdc2a expression in Arabidopsis is linked with competence for cell division. Plant Cell 5:1711-1723[Abstract].

Hemerly, A., de Almeida Engler, J., Bergounioux, C., Van Montagu, M., Engler, G., Inzé, D., and Ferreira, P. (1995) Dominant negative mutants of the Cdc2 kinase uncouple cell division from iterative plant development. EMBO J. 14:3925-3936[Web of Science][Medline].

Huntley, R., Healy, S., Freeman, D., Lavender, P., de Jager, S., Greenwood, J., Makker, J., Walker, E., Jackman, M., Xie, Q., Bannister, A.J., Kouzarides, T., Gutierrez, C., Doonan, J.H., and Murray, J.A.H. (1998) The maize retinoblastoma protein homologue ZmRb-1 is regulated during leaf development and displays conserved interactions with G1/S regulators and plant cyclin D (CycD) proteins. Plant Mol. Biol. 37:155-169[CrossRef][Web of Science][Medline].

Hush, J., Wu, L., John, P.C.L., Hepler, L.H., and Hepler, P.K. (1996) Plant mitosis promoting factor disassembles the microtubule preprophase band and accelerates prophase progression in Tradescantia. Cell Biol. Int. 20:275-287[CrossRef][Web of Science][Medline].

Ingram, G.C., Doyle, S., Carpenter, R., Schultz, E.A., Simon, R., and Coen, E.S. (1997) Dual role for fimbriata in regulating floral homeotic genes and cell division in Antirrhinum.. EMBO J. 16:6521-6534[CrossRef][Web of Science][Medline].

Ito, M., Criqui, M.-C., Sakabe, M., Ohno, T., Hata, S., Kouchi, H., Hashimoto, J., Fukuda, H., Komanine, A., and Watanabe, A. (1997) Cell-cycle-regulated transcription of A- and B-type plant cyclin genes in synchronous cultures. Plant J. 11:983-992[CrossRef][Web of Science][Medline].

Jacobs, T.W. (1995) Cell cycle control. Annu. Rev. Plant Physiol. Plant Mol. Biol. 46:317-339.

Jacqmard, A., De Veylder, L., Segers, G., de Almeida Engler, J., Bernier, G., Van Montagu, M., and Inzé, D. (1999) CKS1At expression in Arabidopsis thaliana suggests a role for the protein in both the mitotic and the endoreduplication cycle. Planta 207:496-504[CrossRef][Web of Science][Medline].

John, P.C.L. (1998) Cytokinin stimulation of cell division: Essential signal transduction is via Cec25 phosphatase. J. Exp. Bot. 49(suppl.):91.

John, P.C.L., Sek, F.J., and Lee, M.G. (1989) A homolog of the cell cycle control protein p34cdc2 participates in the division cycle of Chlamydomonas, and a similar protein is detectable in higher plants and remote taxa. Plant Cell 1:1185-1193[Abstract/Free Full Text].

Kouchi, H., Sekine, M., and Hata, S. (1995) Distinct classes of mitotic cyclins are differentially expressed in the soybean shoot apex during the cell cycle. Plant Cell 7:1143-1155[Abstract].

Leatherwood, J. (1998) Emerging mechanisms of eukaryotic DNA replication initiation. Curr. Opin. Cell Biol. 10:742-748[CrossRef][Web of Science][Medline].

Leyser, H.M.O., Lincoln, C.A., Timpte, C., Lammer, D., Turner, J., and Estelle, M. (1993) Arabidopsis auxin-resistance gene AXR1 encodes a protein related to ubiquitin-activating enzyme E1. Nature 364:161-164[CrossRef][Medline].

Lorbiecke, R., and Sauter, M. (1998) Induction of cell growth and cell division in the intercalary meristem of submerged deepwater rice (Oryza sativa L.). Planta 204:140-145[CrossRef].

Lorbiecke, R., and Sauter, M. (1999) Adventitious root growth and cell-cycle induction in deepwater rice. Plant Physiol. 119:21-30[Abstract/Free Full Text].

Luo, M., Costa, S., Bernacchia, G., and Cella, R. (1997) Cloning and characterisation of a carrot cDNA coding for a WD repeat protein homologous to Drosophila fizzy, human p55CDC and yeast CDC20 proteins. Plant Mol. Biol. 34:325-330[Medline].

Magyar, Z., Bakó, L., Bögre, L., Dedeolu, D., Kapros, T., and Dudits, D. (1993) Active cdc2 genes and cell cycle phase–specific cdc2-related kinase complexes in hormone-stimulated alfalfa cells. Plant J. 4:151-161[CrossRef].

Magyar, Z., Mészáros, T., Miskolczi, P., Deák, M., Fehér, A., Brown, S., Kondorosi, E., Athanasiadis, A., Pongor, S., Bilgin, M., Bakó, L., Koncz, C., and Dudits, D. (1997) Cell cycle phase specificity of putative cyclin-dependent kinase variants in synchronized alfalfa cells. Plant Cell 9:223-235[Abstract].

Martinez, M.C., Jørgensen, J.-E., Lawton, M.A., Lamb, C.J., and Doerner, P.W. (1992) Spatial pattern of cdc2 expression in relation to meristem activity and cell proliferation during plant development. Proc. Natl. Acad. Sci. USA 89:7360-7364[Abstract/Free Full Text].

McKibbin, R.S., Halford, N.G., and Francis, D. (1998) Expression of fission yeast cdc25 alters the frequency of lateral root formation in transgenic tobacco. Plant Mol. Biol. 36:601-612[CrossRef][Web of Science][Medline].

Meskiene, I., Bögre, L., Dahl, M., Pirck, M., Cam Ha, D.T., Swoboda, I., Heberle-Bors, E., Ammerer, G., and Hirt, H. (1995) cycMs3, a novel B-type alfalfa cyclin gene, is induced in the G₀-to-G₁ transition of the cell cycle. Plant Cell 7:759-771[Abstract].

Mews, M., Baluka, F., and Volkmann, D. (1996) Tissue- and development-specific distribution of PSTAIR-proteins in cells of control and wounded maize root apices. J. Exp. Bot. 47:819-829.

Mews, M., Sek, F.J., Moore, R., Volkmann, D., Gunning, B.E.S., and John, P.C.L. (1997) Mitotic cyclin distribution during maize cell division: Implications for the sequence diversity and function of cyclins in plants. Protoplasma 200:128-145[CrossRef].

Mittnacht, S. (1998) Control of pRB phosphorylation. Curr. Opin. Genet. Dev. 8:21-27[CrossRef][Web of Science][Medline].

Nakayama, K.-i., and Nakayama, K. (1998) Cip/Kip cyclin-dependent kinase inhibitors: Brakes of the cell cycle engine during development. Bioessays 20:1020-1029[CrossRef][Web of Science][Medline].

Nigg, E.A. (1995) Cyclin-dependent protein kinases: Key regulators of the eukaryotic cell cycle. Bioessays 17:471-480[CrossRef][Web of Science][Medline].

Peters, J.-M. (1998) SCF and APC: The yin and yang of cell cycle regulated proteolysis. Curr. Opin. Cell Biol. 10:759-768[CrossRef][Web of Science][Medline].

Pines, J. (1996a) Cyclin from sea urchins to HeLas: Making the human cell cycle. Biochem. Soc. Trans. 24:15-33[Medline].

Pines, J. (1996b) Cell cycle: Reaching for a role for the Cks proteins. Curr. Biol. 6:1399-1402[CrossRef][Web of Science][Medline].

Pines, J. (1999) Checkpoint on the nuclear frontier. Nature 397:104-105[CrossRef][Medline].

Plesse, B., Fleck, J., and Genschik, P. (1998). The ubiquitin-dependent proteolytic pathway and cell cycle control. In Plant Cell Division, D. Francis, D. Dudits, and D. Inzé, eds (London: Portland Press), pp. 145–163.

Porat, R., Lu, P., and O'Neill, S.D. (1998) Arabidopsis SKP1, a homologue of a cell cycle regulator gene, is predominantly expressed in meristematic cells. Planta 204:345-351[CrossRef][Web of Science][Medline].

Reichheld, J.-P., Chaubet, N., Shen, W.H., Renaudin, J.-P., and Gigot, C. (1996) Multiple A-type cyclins express sequentially during the cell cycle in Nicotiana tabacum BY2 cells. Proc. Natl. Acad. Sci. USA 93:13819-13824[Abstract/Free Full Text].

Renaudin, J.-P., Colasanti, J., Rime, H., Yuan, Z., and Sundaresan, V. (1994) Cloning of four cyclins from maize indicates that higher plants have three structurally distinct groups of mitotic cyclins. Proc. Natl. Acad. Sci. USA 91:7375-7379[Abstract/Free Full Text].

Renaudin, J.-P., Doonan, J.H., Freeman, D., Hashimoto, J., Hirt, H., Inzé, D., Jacobs, T., Kouchi, H., Rouzé, P., Sauter, M., Savouré, A., Sorrell, D.A., Sundaresan, V., and Murray, J.A.H. (1996) Plant cyclins: A unified nomenclature for plant A-, B- and D-type cyclins based on sequence organisation. Plant Mol. Biol. 32:1003-1018[CrossRef][Web of Science][Medline].

Ruegger, M., Dewey, E., Gray, W.M., Hobbie, L., Turner, J., and Estelle, M. (1998) The TIR1 protein of Arabidopsis functions in auxin response and is related to human SKP2 and yeast Grr1p. Genes Dev. 12:198-207[Abstract/Free Full Text].

Sauter, M. (1997) Differential expression of a CAK (cdc2-activating kinase)-like protein kinase, cyclins, and cdc2 genes from rice during the cell cycle and in response to gibberellin. Plant J. 11:181-190[CrossRef][Web of Science][Medline].

Schuppler, U., He, P.-H., John, P.C.L., and Munns, R. (1998) Effect of water stress on cell division and cell-division-cycle 2–like cell-cycle kinase activity in wheat leaves. Plant Physiol. 117:667-678[Abstract/Free Full Text].

Segers, G., Gadisseur, I., Bergounioux, C., de Almeida Engler, J., Jacqmard, A., Van Montagu, M., and Inzé, D. (1996) The Arabidopsis cyclin-dependent kinase gene cdc2bAt is preferentially expressed during S and G₂ phases of the cell cycle. Plant J. 10:601-612[CrossRef][Web of Science][Medline].

Segers, G., Rouzé, P., Van Montagu, M., and Inzé, D. (1997). Cyclin-dependent kinases in plants. In Plant Cell Proliferation and Its Regulation in Growth and Development, J.A. Bryant and D. Chiatante, eds (Chichester, UK: John Wiley and Sons), pp. 1–19.

Setiady, Y.Y., Sekine, M., Hariguchi, N., Yamamoto, T., Kouchi, H., and Shinmyo, A. (1995) Tobacco mitotic cyclins: Cloning, characterization, gene expression and functional assay. Plant J. 8:949-957[CrossRef][Web of Science][Medline].

Setiady, Y.Y., Sekine, M., Hariguchi, N., Kouchi, H., and Shinmyo, A. (1996) Molecular cloning and characterization of a cDNA clone that encodes a Cdc2 homolog from Nicotiana tabacum.. Plant Cell Physiol. 37:369-376[Abstract/Free Full Text].

Shaul, O., Mironov, V., Burssens, S., Van Montagu, M., and Inzé, D. (1996) Two Arabidopsis cyclin promoters mediate distinctive transcriptional oscillation in synchronized tobacco BY-2 cells. Proc. Natl. Acad. Sci. USA 93:4868-4872[Abstract/Free Full Text].

Soni, R., Carmichael, J.P., Shah, Z.H., and Murray, J.A.H. (1995) A family of cyclin D homologs from plants differentially controlled by growth regulators and containing the conserved retinoblastoma protein interaction motif. Plant Cell 7:85-103[Abstract].

Sorrell, D.A., Combettes, B., Chaubet-Gigot, N., Gigot, C., and Murray, J.A.H. (1999) Distinct cyclin D genes show mitotic accumulation or constant levels of transcripts in tobacco Bright Yellow-2 cells. Plant Physiol. 119:343-351[Abstract/Free Full Text].

Springer, P.S., McCombie, W.R., Sundaresan, V., and Martienssen, R.A. (1995) Gene trap tagging of PROLIFERA, an essential MCM2-3-5–like gene in Arabidopsis.. Science 268:877-880[Abstract/Free Full Text].

Stals, H., Bauwens, S., Traas, J., Van Montagu, M., Engler, G., and Inzé, D. (1997) Plant CDC2 is not only targeted to the pre-prophase band, but is also co-located with the spindle, phragmoplast, and chromosomes. FEBS Lett. 418:229-234[CrossRef][Medline].

Sundaresan, V., and Colasanti, J. (1998). Cyclin-dependent kinases in higher plants: Spatial and temporal control of cell division. In Plant Cell Division, D. Francis, D. Dudits, and D. Inzé, eds (London: Portland Press), pp. 47–65.

Umeda, M., Bhalearao, R.P., Schell, J., Uchimiya, H., and Koncz, C. (1998) A distinct cyclin-dependent kinase–activating kinase of Arabidopsis thaliana.. Proc. Natl. Acad. Sci. USA 95:5021-5026[Abstract/Free Full Text].

Umeda, M., Umeda-Hara, C., Yamaguchi, M., Hashimoto, J., and Uchimiya, H. (1999) Differential expression of genes for cyclin-dependent protein kinases in rice plants. Plant Physiol. 119:31-40[Abstract/Free Full Text].

Wang, H., Fowke, L.C., and Crosby, W.L. (1997) A plant cyclin-dependent kinase inhibitor gene. Nature 386:451-452[CrossRef][Medline].

Wang, H., Qi, Q., Schorr, P., Cutler, A.J., Crosby, W.L., and Fowke, L.C. (1998) ICK1, a cyclin-dependent protein kinase inhibitor from Arabidopsis thaliana interacts with both Cdc2a and CycD3, and its expression is induced by abscisic acid. Plant J. 15:501-510[CrossRef][Web of Science][Medline].

Xie, D.-X., Feys, B.F., James, S., Nieto-Rostro, M., and Turner, J.G. (1998) COl1: An Arabidopsis gene required for jasmonate-regulated defense and fertility. Science 280:1091-1094[Abstract/Free Full Text].

Xie, Q., Sanz-Burgos, A.P., Hannon, G.J., and Gutierrez, C. (1996) Plant cells contain a novel member of the retinoblastoma family of growth regulatory proteins. EMBO J. 15:4900-4908[Web of Science][Medline].

Xiong, W., Pestell, R., and Rosner, M.R. (1997) Role of cyclins in neuronal differentiation of immortalized hippocampal cells. Mol. Cell. Biol. 17:6585-6597[Abstract/Free Full Text].

Yamaguchi, M., Umeda, M., and Uchimiya, H. (1998) A rice homolog of Cdk7/MO15 phosphorylates both cyclin-dependent protein kinases and the carboxy-terminal domain of RNA polymerase II. Plant J. 16:613-619[CrossRef][Web of Science][Medline].

Zhang, K., Letham, D.S., and John, P.C.L. (1996) Cytokinin controls the cell cycle at mitosis by stimulating the tyrosine dephosphorylation and activation of p34^cdc2-like H1 histone kinase. Planta 200:2-12[Web of Science][Medline].

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