Δ133p53β isoform pro-invasive activity is regulated through an aggregation-dependent mechanism in cancer cells

p53 isoform Delta 133p53 beta is reported to promote intrinsic oncogenic functions. Here the authors show Delta 133p53 beta is sequestered as aggregates in an inactive form, while association with interacting partners including p63 isoforms and the CCT chaperone complex promotes Delta 133p53 beta activity, resulting in enhanced cancer cell migration and invasion. The p53 isoform, Delta 133p53 beta, is critical in promoting cancer. Here we report that Delta 133p53 beta activity is regulated through an aggregation-dependent mechanism. Delta 133p53 beta aggregates were observed in cancer cells and tumour biopsies. The Delta 133p53 beta aggregation depends on association with interacting partners including p63 family members or the CCT chaperone complex. Depletion of the CCT complex promotes accumulation of Delta 133p53 beta aggregates and loss of Delta 133p53 beta dependent cancer cell invasion. In contrast, association with p63 family members recruits Delta 133p53 beta from aggregates increasing its intracellular mobility. Our study reveals novel mechanisms of cancer progression for p53 isoforms which are regulated through sequestration in aggregates and recruitment upon association with specific partners like p63 isoforms or CCT chaperone complex, that critically influence cancer cell features like EMT, migration and invasion.