80 P.A. Sabelli · B.A. Larkins
repressor-typeDEL1/E2Fe, which promoted endoreduplication, and its over-
expression, which inhibited endoreduplication in a fashion that was proposed
to counteractE2Fa/DPa(Vlieghe et al. 2005).
That inhibition of RBR1 by phosphorylation is an important mechan-
ism for regulating endoreduplication is indirectly confirmed by the effect
of overexpressing upstream elements controlling the RBR/E2F pathway. In-
creased expression ofCycD3;1and certain CKIs reduces endoreduplication
(De Veylder et al. 2001; Dewitte et al. 2003; Schnittger et al. 2003; Zhou et al.
2003).
One important conclusion from several studies on the impact of the
RBR/E2F pathway on endoreduplication is that it largely depends on the de-
velopmental context. In fact, downregulation of RBR (and upregulation of
E2F) tends to promote cell proliferation in mitotic cells/tissues but to enhance
endoreduplication in endoreduplicating/differentiated cells/tissues (Desvoyes
et al. 2006).
2.3
The Role of the APC/C
Regulated protein degradation through the ubiquitin pathway plays a central
role in cell cycle control. The APC/C is a cullin-based E3 ubiquitin ligase com-
plex involved in the degradation of key cell cycle proteins, thereby regulating
crucial cell cycle transition, such as the metaphase/anaphase transition, mi-
tosis exit, and DNA replication (Nakayama and Nakayama 2006; Peters 2006).
One important activator of APC/C is CDH1, which is a WD40-repeat protein
required for APC/C–substrate interactions (Peters 2006). CDH1 is a conserved
protein, and orthologs, such as Fizzy-related (fzr) and CSS52A, have been
characterized in detail inDrosophila(Sigrist and Lehner 1997) andMedicago
(Cebolla et al. 1999), respectively. Both fzr and CSS52A proteins are required
for endoreduplication, most likely because they regulate the involvement of
APC/C in several processes, the best studied of which is the destruction of mi-
totic cyclins. InMedicago, CSS52A plays a key role in the ploidy-dependent
cell enlargement observed in nitrogen-fixing root nodules resulting from in-
fection by the soil bacterium,Sinorhizobium meliloti(Vinardell et al. 2003).
It also regulates endoreduplication in the giant cells found in root-knot galls,
which are induced by the endoparasitic root-knot nematode,Meloidogyne
incognita(Kondorosi and Kondorosi 2004).
Root nodules develop inMedicagofollowing an indeterminate program.
However, analysis ofCSS52Aorthologs inLotus japonicusandLupinus albus,
which display determinate and intermediate types of root nodule develop-
ment, respectively, has revealed that this gene has a widespread role in linking
endoreduplication to nitrogen fixation in symbiotic cells, regardless of the
mode of nodule morphogenesis and differentiation (Gonzalez-Sama et al.
2006). More recently, CSS52A has also been cloned fromArabidopsis(Tarayre