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 specific consensus sequence within the promoter. It is not clear whether p53 requires a specific DNA binding site in its action as a gene repressor. This report demonstrates that the human BKB1R gene is a p53 target. Expression of p53 in transiently transfected SV40-transformed IMR90 cells strongly suppressed luciferase reporter activity driven by a 1.8 kb BKB1R promoter as well as its minigene. These down-regulations were p53 dose-dependent. p53 reduced both basal and induced promoter activities of the minigene. Expression of p53 abolished the inducibility of the minigene. Induction of endogenous p53 expression by etoposide also inhibited promoter activity and minigene inducibility. Replacing the region containing both the putative p53 binding site and the TATA-box with a basal adenovirus promoter in the 1.8 kb promoter construct did not prevent p53 from inhibiting BKB1R promoter activity. Thus 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 interaction with c-Jun which functions in the inducibility of this gene [Yang et al., 2001].
Yang
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Department of Biochemistry, Boston University School of Medicine, Boston, Massachusetts 02118, USA.
Taylor
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Polgar
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D001665:Binding Sites / Q000187:drug effects / Q000235:genetics; D002461:Cell Line, Transformed; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000235:genetics; D005047:Etoposide / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics; D016758:Genes, jun / Q000235:genetics; D016158:Genes, p53 / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D011401:Promoter Regions, Genetic / Q000235:genetics; D043783:Receptor, Bradykinin B1; D018002:Receptors, Bradykinin / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D016385:TATA Box / Q000187:drug effects / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D015854:Up-Regulation
D043783:Receptor, Bradykinin B1; D018002:Receptors, Bradykinin; D016159:Tumor Suppressor Protein p53; D005047:Etoposide