The well conserved human and murine p53 proteins are tetramers that can activate transcription from templates bearing p53 binding sites. Since the normal function of mammalian p53 is necessary for preserving the stability of genome, we examined the properties of purified Xenopus p53 (Xp53) to determine whether it shares similar biochemical activities. Xp53 was shown to bind specifically to sites containing the p53 consensus sequence derived for human p53. Moreover, Xp53 transactivates reporter genes containing a human p53 response element in vivo. Finally, Xp53 can be cross-linked into tetramers in a manner similar to human p53. However, Xp53 forms hetero-oligomers with human or murine p53 only very ineffectively, in contrast to the efficient hetero-oligomer formation that occurs between human and murine p53 polypeptides. Taken together, our data indicate that sequence specific DNA binding, transcriptional regulation and oligomerization of p53 are common properties of vertebrate p53 proteins, and thus they are likely to be required for the biological activity of the protein.