A novel p53 transcriptional repressor element (p53TRE) and the asymmetrical contribution of two p53 binding sites modulate the response of the placental transforming growth factor-beta promoter to p53.

Previous studies in our laboratory and others identified placental transforming growth factor-beta (PTGF-beta) as an important downstream mediator of DNA damage signaling and a transcriptional target of p53. Here we show that accumulation of PTGF-beta mRNA in response to p53 overexpression is delayed relative to p21(WAF1), whereas the promoters of these genes respond to p53 with similar kinetics. Mutational analyses of two p53 binding sites within the PTGF-beta promoter revealed that site p53-1 (+29 bp) is responsible for as much as 80% of the transcriptional response to p53.