Human p53-p51 (p53-related) fusion protein: A potent BAX transactivator

We recently discovered human p51, a new gene structurally and functionally related to human p53. This gene encodes two major splicing variants, p51A and p51B, which differ in their carboxyl-terminal structure. However, p51A shows strong transactivation potential, while p51B has only weak potential. To clarify the reason for this difference, we made chimeric gene constructs expressing fusion proteins of p53-p51A and p53-p51B, having an N-terminus of p53 and a C-terminus of p51A or p51B, respectively. In a BAX promoter-luciferase assay using p53-deficient SAOS-2 cells, they exhibited up to 30-fold stronger transactivation potential than p53 and p51A themselves, suggesting that the C-terminus of p51B does not simply serve as a repressor. We obtained similar results with p21(WAF1) promoter-reporter plasmids. These chimeras will be valuable tools for gene therapy.