While the wild type form of p53 possesses strong tumor-suppressive activities, the p53 proteins that are commonly mutated in cancer often endow more malignant properties to the cancers they inhabit. There are several lines of evidence supporting such oncogenic gain of function of mutant p53. Compared with p53-null mice, knock-in mice harboring mutant p53 proteins display different and more metastatic tumor spectra. Such mutant proteins are frequently present at far higher levels than the wild-type protein in tumors; in fact, the p53 protein present in the knock-in mice accumulates in tumors despite being inherently unstable in normal tissues,3 suggesting that stabilization of mutant p53 protein is required for its oncogenic activity. Consistently, knockdown of mutant p53 protein in human cancer cell lines leads to reduced cell proliferation, invasion, motility, tumorigenicity and resistance to anticancer drugs. Since epidemiological studies indicate that high levels of mutant p53 proteins correlate with tumor aggressiveness and poorer outcomes, it is important to understand how mutant p53 is stabilized in tumors and how it can be eliminated.
This article proposes questions brought up by earlier studies on mutant p53 proteins
