Translational regulation of p53 as a potential tumor therapy target.
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.
Department of Genetics, Erasmus MC, Dr. Molewaterplein 50, 3015GE Rotterdam, The Netherlands. b.schumacher@erasmusmc.nl
Björn
B
Schumacher
Anton
A
Gartner
D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D016503:Drug Delivery Systems; D004354:Drug Screening Assays, Antitumor / Q000639:trends; D006801:Humans; D009154:Mutation; D009369:Neoplasms / Q000188:drug therapy*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism*
C438244:CEP-1 protein, C elegans; D029742:Caenorhabditis elegans Proteins; D016159:Tumor Suppressor Protein p53