The ubiquitin-proteasome system is inhibited by p53 protein expression in human ovarian cancer cells.

The ubiquitin-proteasome system (UPS) and autophagy provide major cellular pathways for protein degradation. Since the p53 pathway controls autophagy, we investigated whether p53 regulates UPS in ovarian tumour cell lines. A reporter cell line (SKOV3-EGFPu) was established to measure UPS function against a constant genetic background. Transient expression of either wild type or mutant p53 in SKOV3-EGFPu cells reduced UPS activity as compared to vector control. These results, together with those from endogenous p53 expression in seven ovarian cancer cell lines, suggest that expression of both wild-type and mutant p53 protein impairs UPS function. Thus, p53 expression may regulate protein homeostasis by down-regulating UPS function in response to cellular stress.