Insights from a novel p53 isoform in zebrafish want to reel us in, but will we take the bait?

The p53 tumor suppressor has been reported to be expressed as multiple isoforms. In this issue of Genes & Development, Chen and colleagues (pp. 278-290) use a zebrafish model to show that one such isoform, A113p53, is a target for transcriptional activation by p53 and can, in turn, inhibit the activity of the full-length p53 protein, establishing a novel negative feedback loop centered on the p53 locus itself. The challenge will be to determine whether these intriguing results in zebrafish will pave the way for new insights into several perplexing issues in p53 biology that will impact human disease.