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. Synopsis This study shows that both p53 and p21 WAF1 bind to Slug and cooperate to promote the Mdm2‐dependent degradation of Slug, thus suppressing cell invasion. p53 and p21 WAF 1 require each other to suppress cell invasion. Both p53 and p21 bind to Slug and promote its Mdm2‐dependent degradation. This is the first study to elucidate a mechanism involving p53 and p21 cooperation. Graphical Abstract This study shows that both p53 and p21 WAF1 bind to Slug and cooperate to promote the Mdm2‐dependent degradation of Slug, thus suppressing cell invasion.