Translational regulation of p53 as a potential tumor therapy target

Abstract

The tumor suppressor p53 is a central player in apoptosis induction in response to oncogenic stimuli and DNA damage. As activation of p53 has been suggested as a prime strategy for future tumor therapy, inhibition of negative regulators of p53 activity would be a similarly desirable strategy. The small worm Caenorhabditis elegans is a model organism in which many conserved biological pathways, including the core apoptotic machinery, were elucidated. The discovery of a worm p53 homolog cep-1/p53 (which stands for C. elegans p53) that specifically induces apoptosis upon DNA damage through a pathway that is conserved from worm to man opened the way for the use of C. elegans genetics to uncover regulatory mechanisms - and hence novel therapeutic targets - of p53-mediated apoptosis. The authors have recently reported a novel mechanism of C. elegans cep-1/p53 regulation through germ line defective-1-mediated translational repression. This review discusses the potential of the worm system to screen for apoptosis-inducing cancer drugs and to identify novel p53 regulators whose human counterparts might become potential tumor therapy targets.