AbstractThe tightly regulated expression of p53 contributes to genomic stability and transcription of the p53 gene is induced prior to cells entering S‐phase, possibly as a mechanism to insure a rapid p53 response in the event of DNA damage. We have previously described the cloning of an additional 1000 bp of upstream p53 sequences that play a role in the regulated expression of p53, and identified that C/EBPβ‐2 participates in inducing p53 gene expression in a cell cycle regulated fashion. This report deals with the transcriptional regulator, RBP‐Jκ, an essential target of the Notch receptor signaling pathway. It binds to the p53 promoter in a cell cycle regulation fashion and also serves to repress p53 gene expression. We conclude from these findings that the coordinate expression of C/EBPβ‐2 and RBP‐Jκ may be linked to p53 transcription during G0 and as cells move into S‐phase. Because defects in the Notch signaling pathway have been implicated in carcinogenesis, aberrant RBP‐Jκ expression and deregulated regulation of the p53 tumor suppressor could be an important step in some forms of cancers.