Figure 4

Schematic model of RPRM-mediated cell cycle and G2 arrest mechanisms. RPRM has been identified as a transcriptional target for: (1) p53 [4]; (2) histone deacetylase 7/FoxA1 (HDAC7/FoxA1) in an estrogen mediated mechanism [49]; and (3) for epigenetic silencing by hypermethylation of its promoter region [54]. A potential regulation by p73 it has also been proposed [3]. RPRM expression results in inhibited dephosphorylation of Cdc2, suppressing the activation of the Cdc2-Cyclin B1 complex. Thus, inducing cell cycle arrest at G2 suggesting a potential role for RPRM as a tumor suppressor gene [4]. The balance towards cell cycle arrest or proliferation can be shifted by multiple antagonistic effectors, amongst them RPRM. Straight lines with arrowheads indicate activation. Lines with no arrowhead indicate inhibition. Curved arrow on the bottom left indicates dephosphorylation of Cdc2/Cyclin B1 complex. Curved thick arrow on the bottom right indicates nuclear translocation of dephosphorylated Cdc2/Cyclin B1 at the G2/M checkpoint.