The autocrine sPDZD2 protein is a potential p53 activator

Abstract

PDZ domain containing protein 2 (PDZD2) is a ubiquitously expressed six-PDZ domain protein of largely undefined functions. It is cleaved by caspase-3 to form a secreted PDZ domain containing protein 2 (sPDZD2). The sPDZD2 protein has been proposed to function as a potential autocrine prostate tumor suppressor. In this study, we investigated the effects of sPDZD2 on the growth of human prostate, breast and liver cancer cells. The sPDZD2 protein was found to induce senescence of prostate cancer DU145 cells, quiescence of breast cancer MCF-7 and liver cancer Hep-G2 cells, via transcriptional activation of mutant or wild-type p53. Our results indicate that sPDZD2 is worthy of further development as a novel p53 activator for cancer therapy.