Abstract:
The function of p53 is modulated by several transcriptional coactivators that regulate its tumor suppressor activity. Here we report that human transcriptional coactivator PC4 enhances the DNA binding of p53 to its cognate site in vitro and directly interacts with p53 in vivo. In vitro interaction studies demonstrated that the C-terminal 30 amino acids (364 to 393) of p53 strongly interact with PC4. Surprisingly, PC4 also stimulates the sequence-specific DNA binding of p53 with the C-terminal 30 amino acids deleted (p53Delta30), suggesting that PC4 mediates enhancement of p53 DNA binding by a unique mechanism. We also demonstrated that PC4 can stimulate p53- and p53Delta30-mediated transactivation from a p53-responsive promoter. Furthermore, PC4 enhances p53- and p53Delta30-dependent apoptosis by inducing bar (a p53-targeted proapoptotic gene) gene expression. These results establish the first physiological role of PC4 as a transcriptional coactivator.
