The aim of the present study was 2-fold: first, we asked whether destabilization of p53 in vitro is dependent on MDM2-mediated proteasomal degradation or TGase 2-mediated autophagic degradation; second, we asked whether inhibiting MDM2 or TGase 2 in an in vivo RCC model has anticancer effects. Here, TP53 is linked to renal cell carcinoma.