Figure 8.

A schematic model for the cell-cycle regulatory network comprising E2F, p53, miRs and other cell-cycle regulators. Arrows correspond to direct transcriptional activation, whereas bar-headed lines represent direct or indirect inhibition mediated by the following mechanisms: post-transcription gene silencing (miRNAs and their targets), protein binding and inactivation (pocket proteins and E2Fs; as well as CDK inhibitors and CDKs, that in turn inhibit pocket proteins by phosphorylation). The circular arrow represents E2F self-activating ability. Possible mechanisms underlying the repression of E2F by p53 are detailed in the discussion.