Switching the Cell Cycle. Kip-Related Proteins in Plant Cell Cycle Control

Abstract

Cell cycle modes during development. During the growth of a multicellular organism, different cell cycle programs are executed. Typically, in young and less differentiated tissues, a proliferative cell cycle mode occurs by which more cells are generated. As cells differentiate, the rate of cell proliferation decreases and eventually, cells exit the cell cycle. However, before complete withdrawal from the cell cycle, and along with differentiation, many plant and animal cells switch from a mitotic cell cycle to an endoreduplication cycle, in which the nuclear DNA becomes replicated without subsequent nuclear and cellular division, leading to polyploid cells. Cell cycle progression is controlled by an evolutionarily conserved molecular mechanism. A central role is played by kinase complexes, which in their minimal configuration consist of a Ser/Thr kinase (the cyclin-dependent kinase [CDK]) and a regulatory cyclin subunit. CDKs phosphorylate a plethora of substrates, thereby triggering the transition from one cell cycle phase into the next one. The sequential and transient activation of different CDK-cyclin complexes dictates the unidirectional progression through the cell cycle. Because of its importance in growth and development, the CDK-cyclin activity must be strictly controlled. In addition, mechanisms must be operational to ensure a correct exit of the cell cycle in response to antimitogenic stimuli. In yeast and mammals, one of the major regulators of CDK activity are CDK inhibitory molecules (CKIs) that bind and inhibit or sequester CDKs. Recently, putative orthologs of CKI proteins have been identified in plants as well. In this Update, we review the current knowledge on the biochemical properties of plant CKIs and discuss their physiological relevance during plant growth and development. Similar to animals, progression through the cell cycle in plants is regulated by CDKs (De Veylder et al., 2003; Inzé, 2005). In Arabidopsis (Arabidopsis thaliana), at least two classes of CDKs are involved in cell cycle regulation: the A-type CDKs that are represented by only one gene in the model species Arabidopsis (designated Arath;CDKA;1) and the B-type CDK family that has four members, grouped into the B1 (Arath;CDKB1;1 and Arath;CDKB1;2) and B2 (Arath;CDKB2;1 and Arath;CDKB2;2) subclasses (Vandepoele et al., 2002). A-type CDKs display kinase activity from late G1 phase until the end of mitosis, suggesting a role for this particular CDK at both the G1-to-S and G2-to-M transition points (Magyar et al., 1997; Porceddu et al., 2001; Sorrell et al., 2001). A central role for CDKA;1 in controlling cell number has been demonstrated using transgenic tobacco (Nicotiana tabacum) plants with reduced A-type CDK activity (Hemerly et al., 1995). The requirement for Arath;CKDA;1 at least for entry into mitosis has been demonstrated as well by cdka;1 null mutants that fail to progress through the second mitosis during male gametophytic development (Nowack et al., 2005). The group of B-type CDKs displays a peak of activity at the G2-to-M phase transition only (Magyar et al., 1997; Porceddu et al., 2001; Sorrell et al., 2001), suggesting that they play a role at the onset of, or progression through, mitosis. Correspondingly, cells of plants with reduced B-type CDK activity arrest in the G2 phase of the cell cycle (Porceddu et al., 2001; Boudolf et al., 2004a). Although titration of CDK activity by the expression of dominant negative versions of both A- and B-type CDKs resulted in cell cycle defects, no extra cell divisions were stimulated by the overexpression of wild-type Arath;CDKA;1, Arath;CDKB1;1, and Arath;CDKB1;2 alleles in plants (Hemerly et al., 1995; Schnittger et al., 2003; Boudolf et al., 2004a). This observation is consistent with the view that a cofactor is required for full CDK activity, i.e. a cyclin. Cyclins are regulated both transcriptionally and posttranslationally, mainly by controlled protein degradation. By regulating the abundance of specific cyclins, the CDK activity is precisely tuned and targeted to substrates in a spatial and temporal manner. The plant cyclin gene family is very complex. For instance, the Arabidopsis genome codes for at least 49 different cyclins (Vandepoele et al., 2002; Wang et al., 2004) that are classified into seven different subclasses (A, B, C, D, H, P, and T). To date, only a few members of the A-type, B-type, and D-type cyclins have been characterized. With a few exceptions, the expression patterns and activity profiles mimic those of their mammalian counterparts. A-type cyclins are important from S until M phase, while B-type cyclins primarily control the G2-to-M transition. D-type cyclins, whose expression is mainly correlated with the proliferative status of cells, are presumed to drive cells through the G1-to-S checkpoint in a mitogen-dependent manner (De Veylder et al., 2003; Inzé, 2005). In contrast to animals, some evidence points to an additional function of plant D