Background:

The transcription factor, p53, functions as a tumor suppressor protein. In response to stress signals, such as DNA damage, p53 protein induces cell cycle arrest and/or apoptosis. Over half of all human cancers display a reduction in p53 activity due to mutations in the p53 gene, and certain mutants display longevity and can abrogate normal p53 activity. As such, p53 has been a prime target for cancer therapy. To date however, no such small molecule exists and there is a clear need to identify such candidate molecules that restore wild-type activity to mutant p53 proteins. Consequently, new reagents could help to develop and identify new therapeutic compounds.

Technology Description:

The current technology describes a new reagent for the development and identification of novel p53 suppressors. Investigators have identified codon regions responsible for some the most common p53 cancer mutations and have constructed an alternative open reading frame (ORF) in the p53 protein using silent mutagenesis. Changes to specific codons in the constructed p53 ORF caused no amino acid changes from the wild-type p53 protein, but produced additional restriction sites to facilitate cloning with and expression of p53 nucleotide sequences. Additionally, these vectors exhibit better expression in host cell.

File Number: CL0122 

Other Information:

Publication: Proc Natl Acad Sci. 2004; 101:4930-5.