Functions of the Tumor Suppressors p53 and Rb in Actin Cytoskeleton Remodeling

Figure 1

p53 suppresses the cell proliferation mediated by the Rb-E2F pathway. Phosphorylation of Rb by CDK4/6-cyclin D and CDK2-cyclin E causes the dissociation of Rb from E2F to promote cell cycle progression. In response to DNA damage, ataxia telangiectasia mutated (ATM) or ataxia telangiectasia and Rad3-related protein (ATR) are activated and phosphorylate p53 either directly or through Chk1/2. Phosphorylated p53 dissociates from Mdm2 and is thereby stabilized. Active p53 then induces the transcription of its target genes involving p21^WAF1, resulting in the inhibition of CDK2-cyclin E activity.