Mdm2 and p53 are highly conserved from   placozoans to man.
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 1 billion years ago.
Lane
David P
DP
p53 Laboratory (A*STAR), 8A Biomedical Grove, Immunos, Singapore. dplane@p53Lab.a-star.edu.sg
Cheok
Chit Fang
CF
Brown
Christopher
C
Madhumalar
Arumugam
A
Ghadessy
Farid J
FJ
Verma
Chandra
C
D000595:Amino Acid Sequence; D000818:Animals; D017124:Conserved Sequence; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D054909:Placozoa / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D051736:Proto-Oncogene Proteins c-mdm2 / Q000737:chemistry*; D016415:Sequence Alignment; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry*
D016159:Tumor Suppressor Protein p53; D051736:Proto-Oncogene Proteins c-mdm2