Alberto Inga (NIEHS)
Michael Resnick (NIEHS)
- The FIP53 system provides a convenient genetic system for categorizing human mutations. It can also be used to assay potential drug impacts on p53 and for design of such drugs. It can also be used to identify p53 alleles with increased transcriptional capability for various p53 target genes or mutations with different DNA sequence selectivity. Such p53 alleles may be good candidates for p53 based cancer gene therapy.
Mutations in the p53 gene are associated with 50% of all cancers and nearly 80% of the p53 mutations are missense changes. We have developed genetic assays based in yeast that can functionally categorize expressed p53 mutant proteins. The combined assays are referred to as the FIP53 system. Because human p53 cDNA can be conveniently cloned in yeast, the FIP53 system provides a rapid and sophisticated system for the functional analysis of p53 mutants. Four categories of mutations have already been identified. The FIP53 system provides the first in vivo battery for tests that can subdivide many p53 mutations that can occur in humans. In particular, the FIP53 system may allow the identification of rare or new alleles that may function better than the wild type.