Only the smaller transcript was transiently induced by p53 or by genotoxic agents in a p53-dependent manner in a colon carcinoma cell line. The deduced proteins, which are 99% identical to the mouse proteins, contain 551, 491, and 426 amino acids, respectively. RT-PCR analysis detected induction of T2 in response to p53 or genotoxic stress; however, T1 was not induced and T3 was only weakly induced. Western blot analysis showed induction of a predominant 55-kD T2 nuclear protein rather than the 68-kD T1 protein or the 48-kD T3 protein. Sequence analysis predicted, and EMSA and reporter analysis confirmed, that PA26 has a p53-binding site within intron 2. Serum starvation experiments suggested that PA26 may be a member of the growth arrest- and DNA damage-inducible, or GADD, gene family.