The helix-loop-helix containing transcription factor USF binds to and transactivates the promoter of the p53 tumor suppressor gene.

Expression of the wild-type p53 tumor suppressor gene has been found to play an important role in the regulation of cellular proliferation and differentiation. In addition, in many transformed cells and primary tumors, the gene has undergone allelic deletions and mutant forms of the p53 gene are expressed at elevated levels. In defining transcriptional regulatory regions of the p53 gene, we have previously shown that both the human and murine p53 promoters contain a conserved consensus recognition sequence for the basic-helix-loop-helix (bHLH) containing family of DNA-binding proteins. In the murine p53 promoter this element is required for full promoter activity and contains the sequence CACGTG, a sequence identical to the recognition site for the bHLH containing transcription factors c-Myc, USF and TFE3. Here we examine the ability of one of these factors, USF, to bind to the p53 promoter. By assaying the binding activity of in vitro translated USF as well as factors present in nuclear extracts, we conclude that the transcription factor USF binds in a site-specific manner to a CACGTG motif within the murine p53 promoter and represents the major DNA-binding activity observed in nuclear extracts. Elevated levels of USF, generated upon transfection of a vector expressing USF, lead to enhanced activity of the p53 promoter. These findings indicate that USF may play a central role in regulating p53 expression.