Cooperative actions of p21WAF1 and p53 induce Slug protein degradation and suppress cell invasion.

How the p53 transcription factor/tumor suppressor inhibits cell invasion is poorly understood. We demonstrate that this function of p53 requires its direct interaction with p21(WAF1), a transcriptional target of p53, and that both p21 and p53 bind to Slug, which promotes cell invasion. Functional studies reveal that p21 and p53 cooperate to facilitate Mdm2-dependent Slug degradation and that this p53 function is mimicked by p53(R273H), a mutant lacking trans-activating activity. These actions of p21 and p53 are induced by γ-irradiation of cells and also operate in vivo. This is the first study to elucidate a mechanism involving p53 and p21 cooperation.