p73 is a transcriptional activator related to tumor suppressor p53 and regulates differentiation, cell-cycle arrest, and apoptosis. Recently, zebrafish p73 (zp73alpha) was isolated and shown to be required for zebrafish embryogenesis. In this study, we isolated a novel splicing-variant of zp73 mRNA, which was generated by the use of an alternative splicing acceptor site, and designated it as zp73theta. The zp73theta mRNA encoded a carboxy-terminal structure distinct from that of zp73alpha. Whereas the expression level of zp73theta mRNA was much lower than that of zp73alpha in zebrafish adult tissues, it was relatively high and fluctuated during embryogenesis. Using Saos-2 cells for a transient reporter assay, we found that zp73theta, but not zp73alpha, had strong transcriptional activity when the experiments were performed at 34degreesC. In addition, zp73theta had the ability to suppress the growth of Saos-2 cells and to cause the developmental defects in zebrafish. These data indicated that zp73theta could work as a transcriptional activator in zebrafish. (C) 2004 Elsevier Inc. All rights reserved.