The Potential Tumor Suppressor p73 Differentially Regulates Cellular p53 Target Genes1

p73, a potential tumor suppressor, is a p53 homologue. Transient over expression of p73 in cells can induce apoptosis and p21, a cellular p53 target gene primarily responsible for p53-dependent cell cycle arrest. To further characterize the role of p73 in tumor suppression, we established several groups of cell lines that inducibly express p73 under a tetracyclineregulated promoter. By using these cell lines, we found that p73 can induce both cell cycle arrest and apoptosis. We also found that p73 can activate some but not all of the previously identified p53 cellular target genes. Furthermore, we found that the transcriptional activities of p53, p73a, and p73/3 to induce their common cellular target genes differ among one another. These results suggest that p73 is both similar to and different from p53 in their signaling pathways leading to tumor suppression.