p53 Stabilization can be Uncoupled from its Role in Transcriptional Activation by Loss of PTTG1/Securin

HCT116 cells devoid of PTTG1/securin (sec(-/-) HCT116) show a stabilized yet transcriptionally latent form of p53 protein in the absence of DNA damage. Ser15, Ser20 phosphorylation and other post-transcriptional modifications of p53 resolved by 2D gel electrophoresis are comparable to that observed in sec(+/+) HCT116 cells. The difference in degradation was also shown to be independent of the ubiquitin system but reliant on calpains. However, the p53-mediated checkpoint response is active only after genotoxic stress in sec(-/-) HCT116 cells. These findings point to the calpain pathway as a key player to maintain steady state levels of p53 in resting cells without affecting its activity.