Data mining the p53 pathway in the Fugu genome: evidence for strong conservation of the apoptotic pathway.

Abstract

The p53 tumour suppressor gene belongs to a small family of related proteins that includes two other members, p63 and p73. Phylogenetic and functional studies suggest that p63 and p73 are ancient genes that have essential roles in normal development, whereas p53 seems to have evolved more recently to prevent cell transformation. In mammalian cells, a plethora of proteins have been found to specifically regulate p53 activity. The genome of the fish Fugu rubripes has been recently published. It is the second vertebrate genome for which the entire sequence is now available. Phylogenetic studies are essential in order to analyse and define signalling pathways important for cell cycle regulation. The presence or absence of a critical member in any pathway can shed light about the evolution of these pathways. The Fugu genome databank has been analysed for several members of the p53 network, including p53, p63 and p73. A good conservation of the network that regulates p53 stability and apoptosis has been found. We also discovered that some cofactors that cooperate with p53 for apoptosis are also well conserved and belong to multigene families not detected in the human genome.