A novel response element confers p63- and p73-specific activation of the WNT4 promoter

The p53 tumor suppressor gene family consists of three genes, p53, p63, and p73. p53 family proteins share high homology in their DNA-binding domains but exhibit diverse biological functions. In this study, we demonstrated differential target gene activation by specific p53, p63, and p73 induction in Saos2 cells by oligonucleotide microarray expression analysis. We further analyzed the WNT4 promoter, which was induced by p63 and p73 but not p53, in order to clarify the mechanism of differential target gene activation between the three family members. Luciferase analysis showed that the WNT4 promoter harbors two p63/p73 response elements, designated RE1 and RE2. RE1 resembles the canonical p53 response element (tandem repeats of RRRCWWGYYY), located between -141 and -121, while RE2 consists of a GC-rich sequence further downstream. Neither response element alone was able to confer transcriptional activity. It is thus likely that both RE1 and RE2 are necessary in rendering p63/p73-specific activation of the WNT4 promoter.