Tumor suppressor p53 is a regulator of bcl-2 and bax gene expression in vitro and in vivo

Abstract

The p53 tumor suppressor gene product can induce apoptotic cell death through an unknown mechanism. Here we demonstrate that a temperature-sensitive p53 induces temperature-dependent decreases in the expression of the apoptosis-suppressing gene bcl-2 in the murine leukemia cell M1, while simultaneously stimulating increases in the expression of bax, a gene which encodes a dominant-inhibitor of the Bcl-2 protein. Mice deficient in p53 exhibit increases in Bcl-2 and decreases in Bax protein levels in several tissues as determined by immunohistochemical and immunoblot methods. The findings suggest a potential mechanism by which p53 regulates apoptosis, as well as responses to radiation and chemotherapeutic drugs in cancer.