The stiff RhoAd from mevalonate to mutant p53

Mutant p53 oncoproteins (mutp53), produced as result of missense mutations in the TP53 gene, actively promote tumour aggressive traits, metastatic dissemination and chemoresistance. Massive accumulation of mutp53 protein occurs in tumour cells1 and is required for its oncogenic gain of function, indicating pharmacological destabilization of mutp53 as a potential anticancer therapeutic strategy2. In a recent issue of Nature Cell Biology3 we reported that mechanical inputs, transduced by RhoA-dependent cytoskeletal tension, sustain mutp53 protein stability and that blocking this axis with mevalonate (MVA) pathway inhibitors curbs mutp53 accumulation in tumours