384 C. Gutierrez
this role. Virus-induced transcriptional silencing of the tobaccoRBRgene ex-
tends cell proliferation activity and induces extra endocycles in leaves (Park
et al. 2005). Similar phenotypes are observed after inactivation ofArabidop-
sisRBR by expressing the geminivirus RepA protein (Desvoyes et al. 2006).
The consequences of RBR inactivation depends on the developmental stage
and the cell type, e.g., hyperplasia in young leaves and extra endocycles in
older leaves (Desvoyes et al. 2006). These effects are mediated by an increase
in E2Fa and E2Fc activities, suggesting that they act in the same pathway
to regulate the transcriptional program during development. Stimulation of
cell division in the leaf epidermis is also the outcome of altering other, less
well-characterized pathways. Thus, overexpression of theSTRUWWELPETER
(SWP) gene (Autran et al. 2002) or silencing ofDEKgene (a calpain homo-
logue) expression in tobacco also leads to a hyperplastic phenotype (Ahn
et al. 2004). Although the mechanism behind these effects is not fully under-
stood, these mutant plants have an altered pattern of expression of several
cell cycle genes. The range of control pathways that operate in conjunction
with the RBR/E2F complexes seems to increase as new data are obtained.
Thus, pull-down experiments have shown thatArabidopsisRBR and FIE in-
teract, supporting a role of FIE-containing polycomb complexes in inhibiting
premature division of the central cell of the embryo sac (Mosquna et al. 2004).
Compelling evidence indicates that RBR, in a manner analogous to RB
in animal cells, modulate the activity of E2F-DP transcription factors (Ko-
renjak and Brehm 2005). E2F transcription factors were originally identified
by their ability to interact and activate the human adenovirus E2 promoter
(Helin et al. 1992). Its partner, DP, was identified soon afterwards (Helin
et al. 1993). E2F transcription factors regulate the expression of a variety
of genes required for cell cycle progression and their activity is modulated
by the retinoblastoma (RB) protein. About ten years ago, the identification
of proteins containing a LxCxE amino acid motif (Soni et al. 1995; Dahl
et al. 1995; Xie et al. 1995) strongly pointed to the, somewhat unexpected,
existence of a RB-related pathway in plants. This was fully confirmed with
the identification of the first plant RBR (Xie et al. 1996; Grafi et al. 1996),
E2F (Ramirez-Parra et al. 1999; Sekine et al. 1999) and DP (Ramirez-Parra
and Gutierrez 2000; Magyar et al. 2000). These studies were followed by
others that have led to the identification of a large family of E2F-DP fac-
tors in different plant species, includingArabidopsis, rice, maize, tobacco,
carrot, and the unicellular algaeChlamydomonas reinhardtiiandOstreococ-
cus tauri(Ramirez-Parra et al. 2007). ThreeArabidopsisE2F, named E2Fa,
E2Fb and E2Fc, share a domain organization similar to that of human E2F1-5
(Shen 2002; Ramirez-Parra et al. 2007). The other three members, known as
E2Fd/DEL2, E2Fe/DEL1 and E2Ff/DEL3, are atypical since they contain a du-
plicated DNA binding domain and function independently of DP.
Constitutive overexpression of bothE2FaandDPainduces cell division
and endoreplication (De Veylder et al. 2002; Rossignol et al. 2002). The E2Fa-