p73 tumor suppressor protein: a close relative of p53 not only in structure but also in anti-cancer approach?

Abstract

The discovery of the p53 tumor suppressor protein in 1979 shed new light on cancer cell biology and introduced a trend in cancer research focusing on p53-like proteins. This in turn led to the discovery of two homologous proteins of p53-p63 in 1998 and p73 in 1997. The p53 family members are mainly involved in apoptosis induction under cellular stress, but also in early embryonic developmental processes. The p63 and p73 proteins activate the transcription of a number of p53 target genes. The precise role of p63 in cancer cells is not fully revealed yet, unlike that of p53 and p73. The p53 tumor suppressor protein is found inactive in approximately 50% of human cancers. However, p73 is not as often inactivated in tumors. Of importance, transcriptionally active forms of p73 induce apoptosis in cancer cells independent of p53 status. Moreover, the regulatory mechanisms governing p73 stability in cells are well described. These features promoted the research concerning p73-targeted anti-cancer treatment. The p73 protein is subject to sophisticated activatory and inhibitory regulatory mechanisms. The up-to-date anti-cancer compounds targeting p73 protein in vitro inhibit its negative regulators, which leads to the activation of p73 pro-apoptotic function in cancer cells. In the current review we present the recent scientific findings on p73 regulation in cells and the newest anti-cancer strategies concerning its tumor suppressor function.