The 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 ensure 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 we have demonstrated play a role in the regulated expression of p53. As described in an earlier report, we preliminarily identified that a member of the CAAT/enhancer-binding protein (C/EPB) family of transcription factors may play a role in regulating p53. Here we have demonstrated that a particular C/EBPbeta isoform, C/EBPbeta-2, efficiently binds to the p53 promoter and induces its expression in a fashion that reflects the pattern of p53 expression seen as cells are induced to enter S phase and is absent from cells that are defective in proper p53 regulation. We conclude from these findings that C/EBPbeta-2 plays a central role in the regulating of p53 transcription during the transition into S phase.
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