Roles of p53 in mammals have been extensively studied but little is known about its functions in lower vertebrates. We have cloned and characterized the p53 gene from tilapia (Oreochromis niloticus), expressed it in Escherichia coli, generated a rabbit polyclonal antibody and examined the gene's expression patterns at both transcript and protein levels. The full-length p53 cDNA was 1288 bp with an ORF of 1,138 bp, encoding a polypeptide of 364 amino acids. The gene contains all four classical p53 family signature motifs but has low sequence similarity with other p53 genes. It was constitutively transcribed in all tissues examined, most abundantly in liver and blood cells. In addition, ATM, p53 and Bax proteins, associated with DNA damage responses and apoptosis, were all upregulated in tilapia liver after treatment with the stress inducers etoposide and CdCl2. Tilapia p53 is thus both a constitutive and inducible acute-phase protein that is cooperatively activated via the ATM-p53 pathway in responses to stress and DNA-damaging signals.