G1/S Transition and the Rb-E2F Pathway 63
group of timely activated genes includingArath;CYCD3;1(Masubelele et al.
2005). In alfalfa,Medsa;CYCA2;1is responsive to auxin and expressed to
a constant level during the cell cycle, and its antisense-expression inhibited
regeneration of somatic embryos, suggesting a role in meristem function
(Roudier et al. 2000; 2003). Further in supporting a role in G1/S transi-
tion, Medsa;CYCA2;1 protein binds CDKA and Rb (Retinoblastoma protein)
(Roudier et al. 2000). Together these studies demonstrate that CYCAs from
different plant species have important roles at the G1/S transition. Genetic
study identified a role forArath;CYCA1;2in meiosis during pollen forma-
tion (Wang et al. 2004b). The absence of detectable effects on mitotic division
in the mutanttam, which is allelic toArath;CYCA1;2(Wang et al. 2004b),
might be explained by functional redundancy or developmental compensa-
tion by other genes.
2.3
ICKs/KRPs
Arabidopsiscontains seven ICKs/KRPs but no homologs to the animal INK4
family inhibitors (Verkest et al. 2005a). In animals INK4 specifically interacts
with CDK4 and CDK6 (Sherr and Roberts 2004), the simultaneous absence
of INK4, CDK4 and CDK6 homologs inArabidopsisfurther strengthens dif-
ferences between plants and animals in the control of the G1/S transition.
The assumption that plant ICKs/KRPs have an important function in the
G1/S transition is supported by the following findings: (1) ICKs/KRPs in-
hibit CDK activity both in vitro and in vivo; (2) ICKs/KRPs bind CDKA
and CYCDs; (3) overexpression of ICKs/KRPs reduces cell division rate and
affects endoreplication in a dosage-dependent manner; (4) mutant pheno-
type by ICKs/KRPs-overexpression can be attenuated by co-overexpression
of CYCDs (Verkest et al. 2005a; references therein). Interestingly, not only
CYCD-CDK but also CYCA-CDK activity is inhibited by ICKs/KRPs in maize
(Coelho et al. 2005), implying a broader role of ICKs/KRPs in the G1/S
transition.
In yeast and in animals, proteasomal degradation of inhibitors which
releases active cyclin-CDK complexes constitutes an important mechan-
ism of activation of the G1/S transition. The ubiquitin ligase SCF (Skp1-
Cullin/CDC53-F box protein) which is specifically responsible for such degra-
dation is conserved in plants and essential for cell division (Shen et al. 2002;
Thomann et al. 2005). TheArabidopsisICK2/KRP2 was shown to be phos-
phorylated by both CDKA- and CDKB-type kinases, resulting in proteasome-
dependent degradation (Verkest et al. 2005b). Thus, both regulated transcrip-
tion and regulated proteolysis contribute to the regulation of activity of the
G1/S cell-cycle machinery for an integrated cell division within plant growth
and development as well as in response to environmental cues.