The amino terminal of human P51/TAp63, a P53 homologue, possesses a transactivation domain involved in the activation of its target genes by binding to DNA elements responsive to the p53 protein family. Using a series of amino terminal deletions, the transactivation domain was mapped between amino acid residues 50 to 69, This domain also regulates protein stability in a proteasome-dependent manner, and Ser51 and Ser68 were found to be essential for this stability. Our results suggest that P51 activity is greatly affected by protein stability.