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Mdm2 and p53 are highly conserved from placozoans to man

David P. Lane, Chit Fang Cheok, Christopher Brown, Arumugam Madhumalar, Farid J. Ghadessy and Chandra Verma

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The p53 protein is the most commonly mutated tumor suppressor gene in man. Understanding of its evolutionary origins have been enhanced by the recent discovery of p53 family genes in the sea anemone Nematostella vectensis. This amino acid sequence conservation has been reflected in biological activity since the early p53 proteins, like their human counterparts, are responsible for DNA damage-induced cellular apoptosis, albeit restricted to the germ cell compartment in model organisms such as the nematode and fruit fly. In vertebrates from zebrafish to man the function of p53 is tightly and absolutely constrained by a negative regulator Mdm2. However the Mdm2 gene has not been detected in the genome of the model nematode (C. elegans) and insect (D. melanogaster) species. We have found that the p53 gene and the Mdm2 gene are present in Placozoans, one of the simplest of all free living multi-cellular organisms, implying that both proteins arose much earlier in evolution than previously thought. Detailed sequence analysis shows the exceptional retention of key features of both proteins from man to placazoan implying that the p53-Mdm2 interaction and its regulation have been conserved from a basal eumetazoan since the pre-cambrian era over one billion years ago.

Authors

David P. Lane Corresponding author: dplane@p53Lab.a-star.edu.sg

Agency for Science, Technology and Research; Singapore

Chit Fang Cheok

Agency for Science, Technology and Research; Singapore

Christopher Brown

Agency for Science, Technology and Research; Singapore

Arumugam Madhumalar

Agency for Science, Technology and Research; Singapore

Farid J. Ghadessy

Agency for Science, Technology and Research; Singapore

Chandra Verma

Agency for Science, Technology and Research; Singapore

This is an open-access article

 Download PDF

If the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.