DNA-binding Properties of the p53 Tumor Suppressor Protein

Abstract

The p53 tumor suppressor gene product plays a pivotal role in cells by transmitting a signal from damaged DNA to genes that regulate the cell cycle and apoptosis (Donehower and Bradley 1993; Levine 1993; Prives and Manfredi 1993). Central to its function in this capacity is its ability to bind specifically to DNA (Vogelstein and Kinzler 1992). p53 activates transcription from promoters that contain p53-binding sites (Vogelstein and Kinzler 1992). Identified genes that contain such p53 response elements, which are activated in cells upon DNA damage and subsequent accumulation of p53, include GADD45 (Kastan et al. 1992), mdm2 (Wu et al. 1993), and WAF1/p21 (El-Deiry et al. 1993). The interest in p53 that stems from its unique and critical role in a DNA damage signal transduction pathway is reinforced by, and indeed possibly subsidiary to, the fact that mutation of the p53 coding sequence occurs with extraordinarily high frequency in...