The TP53 signaling network in mammals and worms

Abstract

The nematode worm Caenorhabditis elegans has been an invaluable model organism for studying the molecular mechanisms that govern cell fate, from fundamental aspects of multicellular development to programmed cell death (apoptosis). The transparency of this organism permits visualization of cells in living animals at high resolution. The powerful genetics and functional genomics tools available in C. elegans allow for detailed analysis of gene function, including genes that are frequently deregulated in human diseases such as cancer. The TP53 protein is a critical suppressor of tumor formation in vertebrates, and the TP53 gene is mutated in over 50% of human cancers. TP53 suppresses malignancy by integrating a variety of cellular stresses that direct it to activate transcription of genes that help to repair the damage or trigger apoptotic death if the damage is beyond repair. The TP53 paralogs, TP63 and TP73, have distinct roles in development as well as overlapping functions with TP53 in apoptosis and repair, which complicates their analysis in vertebrates. C. elegans contains a single TP53 family member, cep-1, that shares properties of all three vertebrate genes and thus offers a simple system in which to study the biological functions of this important gene family. This review summarizes major advances in our understanding of the TP53 family using C. elegans as a model organism.