The wild type p53 tumor suppressor protein transactivates genes carrying p53 responsive elements and represses several TATA containing promoters. We report in vivo gene regulation assays where deletion of the N-terminal 75 residues (delta N75) results in loss of transactivation of p53CON and repression of an HPV 6 reporter. In contrast, removal of the C-terminal 75 (delta C75) amino acids resulted in a truncated protein capable of trans-activating p53CON but not able to repress the HPV 6 reporter. In vitro protein association assays revealed that the delta N75 protein, but not the delta C75 truncated protein, could oligomerize with the wild type p53 protein. Co-transfection assays with wild type p53 showed that the delta N75 mutant protein has a dominant negative effect on trans-activation function. However, it does not affect the ability of wild type p53 to repress transcription from the HPV 6 receptor. The delta C75 protein had no effect on the ability of the wild type p53 to activate p53CON or repress the HPV 6 reporter. These results suggest that distinct regions of p53 have a differential role in transcriptional activation and repression functions.