While the presence, in the invertebrates, of genes related in sequence and function to the vertebrate p53 family has been known since the discovery of the fly Drosophila melanogaster Dmp53 and the worm Caenorhabditis elegans cep-1 gene, the failure to discover homologs of the essential vertebrate negative regulator of p53 Mdm2 in these species led to the false assumption that Mdm2 was only present in vertebrates. Very recently, clear homologs of Mdm2 have been discovered in a wide range of invertebrate species, raising a series of interesting questions about the evolution of the p53 pathway. Here, a personal account of the discovery of Mdm2-like genes in the Placozoa and Arthropoda is used to speculate on aspects of the evolution, structure, and function of the p53 pathway.
Keywords: E3 ligase; Mdm2; RING domain; evolution; invertebrate; p53 interaction.