from differentiated somatic tissues varies considerably from species to species [5]. The induction of cell
division in differentiated cells (G 0 to G 1 transition) is the first critical step in the regeneration process.
Hence, studies on cell cycle regulation are likely to provide some clues to mechanisms that regulate plant
regeneration [10,11].
In yeast and animal systems considerable advances have been made in our understanding of the con-
trol of different phases of the cell cycle using yeast and animal systems [12–15]. The combination of ge-
netic, biochemical, and molecular approaches has resulted in identification of decision points in the cell
cycle and key regulatory proteins that control progression through the decision points. A number of ex-
cellent reviews describing the cell cycle regulation in fungi [13,16,17], insects [4], and mammalian cells
[12,14,15,18] are available. Cell cycle research in plants is in its early stages. However, research during
the last several years shows that at least some of the key cell cycle regulatory proteins are structurally and
functionally conserved between plants and other unicellular and multicellular eukaryotes. Our goal here
is to summarize what is known about cell cycle regulation in plants and some of the unique aspects of cell
cycle in plants. Because of limited information with plant systems and considerable similarity in cell cy-
cle regulation across phylogenetically divergent species, it is necessary that we present an overview of
cell cycle regulation in fungi and animal systems.
Largely based on genetic analysis in yeast, the eukaryotic cell cycle is believed to be regulated at two
major decision points—a point late in G 1 called START, which is where a cell commits itself to DNA
replication, and G 2 /M phase transition [16]. Studies with fungi and animal systems indicate that both these
transitions as well as progression of cells through S phase are controlled by protein kinases whose activ-
ity is regulated in a very complex manner [13,14,16].
II. KEY PROTEINS INVOLVED IN CELL CYCLE REGULATION
A. Cyclin-Dependent Kinases
In multicellular organisms there is a family of closely related protein kinases that function at different cell
cycle transitions. This family of protein kinases is called cyclin-dependent kinases (Cdks) as the activity
of these enzymes is dependent on interaction with a member of the cyclin family of proteins (see later).
Cdks catalyze the transfer of phosphate from ATP to specific serine or threonine residues on regulatory
and structural proteins, the aggregate modification of which drives cells through cell cycle checkpoints
[19]. The first vertebrate Cdk, p34CDC2(Cdk1), was identified as the catalytic subunit of maturation-pro-
moting factor (MPF) [20]. In vertebrates, nine Cdks (including Cdk1) have been identified based on their
sequence and ability to complement yeast mutants or to interact with cyclins (Table 1) [21–23]. Cdk2
closely resembles Cdk1 [24–26]. Cdk3, Cdk5, and Cdk6 were identified in humans on the basis of their
sequence similarity to a conserved stretch of residues (PSTAIRE motif) in Cdk1 [27]. Cdk5 is the only
Cdk that is active exclusively in nondividing cells [28]. Cdk4 was first identified as a member of the pro-
tein-serine kinase family and designated as p34PSK-J3[29]. The same gene was later isolated from mouse
macrophage cells in early G 1 and classified as Cdk4 as it was found to act in a cyclin-dependent manner
[30]. A Xenopusp34cdc2-related protein was shown to be a subunit of CAK (cdc2 activating kinase), an
enzyme necessary for the activation of p34cdc2by phosphorylation [31]. When this protein was shown to
associate with a novel cyclin (cyclin H), it was classified as Cdk7 [32]. Cdk8 is a 53-kDa protein con-
taining sequence motifs and subdomains of serine/threonine-specific kinases [23]. Cdk9 has a modified
PSTAIRE motif (PITALRE) and has been shown to be involved in transcription regulation rather than
cell cycle control as have other Cdks such Cdk8 [33,34]. Cdk7 has also been shown to be involved in tran-
scription regulation as well as cell cycle control [35–37]. Table 1 lists the known Cdks, conserved motifs,
and, where known, the cyclin or other regulating protein they associate with. The interactions and func-
tions will be explained in more detail in the following sections.
B. Cyclins
Cyclins, a family of proteins named for their cyclical expression and degradation, play an important role
in the cell division cycle. Cdks by themselves are inactive and are activated by their association with cy-
clins [38]. Cyclins were first discovered in clams and sea urchins as a class of proteins that accumulate to
high levels in interphase and are abruptly destroyed at the end of M phase [38–40]. Proper timing of cy-
clin expression is controlled at the transcriptional level [41] and by ubiquitin-mediated degradation of cy-
230 REDDY AND DAY