Mdm2 Regulates p53 Independently of p19 in Homeostatic Tissues

Tumor suppressor proteins must be exquisitely regulated since they can induce cell death while preventing cancer. For example, the p19 tumor suppressor (p14 in humans) appears to stimulate the apoptotic function of the p53 tumor suppressor to prevent lymphomagenesis and carcinogenesis induced by oncogene overexpression. Here we present a genetic approach to defining the role of p19 in regulating the apoptotic function of p53 in highly proliferating, homeostatic tissues. In contrast to our expectation, p19 did not activate the apoptotic function of p53 in lymphocytes or epithelial cells. These results demonstrate that the mechanisms that control p53 function during homeostasis differ from those that are critical for tumor suppression. Moreover, the Mdm2/p53/p19 pathway appears to exist only under very restricted conditions.