Cell cycle-related transformation of the E2F4-p130 repressor complex

Conditional Deletion of the Retinoblastoma (Rb) Gene in Ovarian Granulosa Cells Leads to Premature Ovarian Failure

“…4). Localization of RBL2 in both the nucleus and cytosol has been previously reported, and it has been suggested that RBL2 may play different roles and be subjected to differential regulation in the two compartments (57). We found that, in addition to increased E2f1, Rb cKO follicles expressed significantly higher levels of the transcription factor E2f5, an E2F family member known to interact with RBL2/p130 (Table 3).…”

Regulation of Rad51 promoter

“…36 This same sequence between −31 to −21 could then activate Rad51 expression via the oncogenic BCR/ABL fusion tyrosine kinase constitutively activating STAT5 transcription. 25,37,38 Additionally, possible changes in CpG island methylation states between base pairs −116 to -92 as well as translational/posttranslational regulation were suggested to affect Rad51 expression and lead to the differential between cancerous and non-cancerous cells.…”

E2F4 (E2F transcription factor 4, p107/p130-binding)

“…However, E2F4 migrates as an heterogeneous set of bands between 57-64 kDa which are associated with extensive phosphorylations (Beijersbergen et al, 1994;Ginsberg et al, 1994;Vairo et al, 1995;Gaubatz et al, 2001;Popov et al, 2005;Araki et al, 2008;Scime et al, 2008;Van Hoof et al, 2009;Litovchick et al, 2011). Unlike E2F1, E2F2 and E2F3, which exhibit a cyclin A binding domain at their N-terminus, E2F4 has a truncated N-terminus and therefore does not harbor this domain (Beijersbergen et al, 1994;Sardet et al, 1995).…”

“…E2F4 is the only E2F possessing a stretch of 13 consecutive serine residues in its transactivation domain (Sardet et al, 1995). Numerous publications infer that E2F4 is a phosphorylated protein (Beijersbergen et al, 1994;Ginsberg et al, 1994;Vairo et al, 1995;Gaubatz et al, 2001;Popov et al, 2005;Scime et al, 2008) although only a few have identified specific phosphorylation sites: T14 and S16 are phosphorylated residues (Van Hoof et al, 2009); S281 and S285 are phosphorylated by IKKα and IKKβ and enhance E2F4 nuclear localization and DNA-binding of the E2F4/p130 complex in human primary fibroblasts (Araki et al, 2008); S384 is phosphorylated in the DREAM or MMB complexes (Litovchick et al, 2011). Thereafter, genes required for DNA synthesis and cell cycle progression are induced, allowing cells to enter S-phase and pursue their cell cycle (Cobrinik, 2005;Malumbres and Barbacid, 2009). In addition to pocket protein-mediated regulation, E2F4 is also controlled by other mechanisms such as phosphorylation, antisenses (Yochum et al, 2007), reactive oxygen species (Kim and Lee, 2010), cofactors and mainly by its subcellular localization.…”

“…Indeed, E2F4 protein levels are not significantly modulated during cell cycle progression; however, its nuclear localization is tightly regulated (Lindeman et al, 1997;Verona et al, 1997;Deschenes et al, 2004) (see below). Furthermore, many studies have reported E2F4 phosphorylation but only a few have associated these phosphorylation events with a specific function (Beijersbergen et al, 1994;Ginsberg et al, 1994;Vairo et al, 1995;Gaubatz et al, 2001;Popov et al, 2005;Araki et al, 2008;Scime et al, 2008;Van Hoof et al, 2009;Litovchick et al, 2011). For example, Araki et al, 2008 showed that E2F4 phosphorylation by IKKα and/or IKKβ leads to increased binding of the E2F4/p130 complex to DNA in TIG-3 human primary fibroblasts.…”