The responsiveness of ARF to the Rb pathwayproliferative signaling characteristic of zebrafish fin regeneration implies thatsimilar mitogenic signaling occurring in a mammalian context would be detected asaberrant, activate ARF–MDM2–TP53 tumor suppressor mechanisms, and oppose regeneration.Our findings are compatible with previous mouse studies showing that ARF is a potenttumor suppressor that is dispensable for normal development (Serrano et al., 1996; Kamijo etal., 1997). Here, TP53 is linked to neoplasm.