Isolation of p53-target genes and their functional analysis

Mutations of the p53 gene are the most common genetic alterations found in human cancers, and are known to play crucial roles in tumor development and progression. The p53 gene encodes a protein functioning as a transcription factor, and the biological functions of p53 are manifested through the activities of its downstream genes. Identification of these downstream genes involved in the p53-signaling pathway should provide more detailed insight into the molecular mechanisms that mediate tumor-suppressor activities, as well as various responses to cellular stress. We have been attempting to isolate p53-target genes by means of various approaches, including differential display, cDNA microarray analysis, and direct cloning of the p53-binding sequences from human genomic DNA. Here I review our recent work on isolation of p53-target genes and their functional analysis. The physiological functions of p53-target genes include apoptosis (GML, p53AlP1, and STAG1), DNA repair (p53R2), inhibition of angiogenesis (BAl1), re-entry into the cell cycle (p53RFP), oxidative stress (CSR), and determination of cell fate (p53RDL1).