64 W.-H. Shen
3
The Rb-E2F Pathway
In plants like in animals, the Rb-E2F pathway is recognized as a major mech-
anism bridging the activity of the cell-cycle machinery to transcription, par-
ticularly at the G1/S transition. The transcription factor E2F (the adenovirus
E2-promoter-binding factor) functions as a heterodimer with a DP (Dimer-
ization Partner) protein and controls the transcription of a wide variety of
genes, among others genes involved in cell-cycle progression, DNA replica-
tion and repair. Hypophosphorylated Rb binds and inactivates E2F in tran-
scription. Phosphorylation of Rb results in the release of E2F that activates
transcription, which irreversibly commits cells to undergo DNA replication
(S-phase). Many studies, in mammals as well as in plants, indicate that from
late G1, in response to developmental or mitogenic cues, Rb is hyperphospho-
rylated by cyclin-CDK kinases that triggers G1/S transition (Fig. 1).
3.1
E2Fs
Arabidopsiscontains eight proteins that can be classified by sequence ho-
mology into the E2F, DP and DEL (DP and E2F-Like) groups (Shen 2002).
The three members of the E2F-group, AtE2Fa, AtE2Fb and AtE2Fc, exhibit
an overall domain organization similar to the animal E2F1-5 proteins, in-
cluding a highly conserved DNA-binding domain, a moderately conserved
leucine-zipper dimerization domain, and a C-terminal trans-activation do-
main embracing a conserved Rb-binding site. While AtE2Fc, which contains
a shorter C-terminal domain, was shown to function as a transcriptional re-
pressor, to be abundant in arrested cells and to be degraded by proteasome
upon cell-cycle stimulation (del Pozo et al. 2002), AtE2Fa and AtE2Fb were
shown as transcriptional activators stimulating cell division (De Veylder et al.
2002; Magyar et al. 2005). The two members of the DP-group, AtDPa and
AtDPb, contain a conserved DNA binding and leucine zipper dimerization
domain and function, at least for AtDPa, as dimers with AtE2Fa and AtE2Fb
in transcriptional activation (De Veylder et al. 2002; Magyar et al. 2005). Con-
sistent with their hypothesized roles in the G1/S transition, AtE2Fa-DPa or
AtE2Fb-DPa overexpression enhanced the S-phase and resulted in a cellular
phenotype very similar to that produced by Arath;CYCD3;1, Arath;CYCA2;3
or Nicta;CYCA3;2 overexpression. The other three members belonging to the
DEL-group, AtDEL1, AtDEL2 and AtDEL3, contain duplicated DNA-binding
domains but lack the other conserved regions of the E2F- and DP-group.
They bind to DNA as monomers and likely function as antagonists of E2F-
DP dimers, probably by competition on the E2F binding site. Both AtDEL3
(also called E2Ff ) and AtDEL1 are primarily involved in cell differentia-
tion rather than in cell division (Ramirez-Parra et al. 2004; Vlieghe et al.