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

Abstract

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). 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. Classification of CDKs in Plants At the transcriptional level. Question marks denote uncertainty. Classification of CDKs in Plants At the transcriptional level. Question marks denote uncertainty. 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 substitute the functions of their yeast and animal homologs (Tables 1and 2; Hata et al., 19