p53 down-regulates human bradykinin B1 receptor gene expression

The tumor suppressor, p53, has been shown to transcriptionally activate or silence a number of target genes. As an activator, p53 relies on its specif ic consensus sequence within the promoter. It is not clear whether p53 requ ires a specific DNA binding site in its action as a gene repressor. This re port demonstrates that the human BKB1R gene is a p53 target. Expression of p53 in transiently transfected SV40-transformed IMR90 cells strongly suppre ssed luciferase reporter activity driven by a 1.8 kb BKB1R promoter as well as its minigene. These down-regulations were p53 dose-dependent, p53 reduc ed both basal and induced promoter activities of the minigene. Expression o f p53 abolished the inducibility of the minigene. Induction of endogenous p 53 expression by etoposide also inhibited promoter activity and minigene in ducibility. Replacing the region containing both the putative p53 binding s ite and the TATA-box with a basal adenovirus promoter in the 1.8 kb promote r construct did not prevent p53 from inhibiting BKB1R promoter activity. Th us suppression by p53 is not mediated by competition with the TATA-binding protein and is not through interaction with the putative p53-binding site. p53 also does not appear to suppress BKB1R gene expression through interact ion with c-Jun which functions in the inducibility of this gene [Yang et at ., 2001].