Expanding complexity of p53

25 years after the initial discovery of p53, Dr. David Lane and colleagues at the University of Dundee have discovered multiple isoforms of the p53 tumor suppressor protein.

Their paper, which will be released online ahead of print in Genes & Development, establishes that, like the other p53 family members p63 and p73, p53 exists in human cells in at least six different isoforms. Dr. Lane and colleagues identified a heretofore unrecognized internal promoter and alternative splice exons in p53 mRNA.

While further research is needed to delineate how the various p53 isoforms affect p53 tumor suppressor activity, the scientists did establish that some p53 isoforms can modulate p53 transcriptional activity and p53-induced cell death. Interestingly, Prof. Lane and colleagues observed that p53 isoforms are abnormally expressed in breast tumors presenting no mutation of the p53 gene. David Lane and Jean-Christophe Bourdon, group leader in David Lane’s laboratory, consider the discovery of p53 isoforms to be “a major breakthrough in the understanding of cancer formation.

The determination of p53 isoforms expression in human cancers will help to identify patients at risk of developing aggressive cancer and to define their drug sensitivity in order to treat the patient with the most efficient drug.”