CHARACTERIZATION OF P53 OLIGOMERIZATION DOMAIN MUTATIONS ISOLATED FROM LI-FRAUMENI AND LI-FRAUMENI LIKE FAMILY MEMBERS

p53 is a tumour suppressor gene which functions as a transcription fac tor to upregulate genes for growth arrest and apoptosis following DNA damage. p53 mutations are associated with Li-Fraumeni and Li-Fraumeni like syndromes. Recently mutations of the oligomerization domain have been isolated from an LFS and an LFL family affecting respectively cod on 344 (Leu to Pro) and 337 (Arg to Cys), The present study was design ed to determine the affect of these mutations on the function of pJ3 p rotein, p53 344 Leu to Pro existed only in a monomeric form and could not bind to DIVA. It was inactive at inducing apoptosis, transactivati ng luciferase from a bar promoter and inhibiting cell growth. In contr ast, p53 337 Arg to (Cys could form tetramers and could bind to DNA, H owever, p53 337 Arg to Cys was not fully active and could only induce apoptosis, transactivate luciferase from a bax promoter and inhibit ce ll growth with approximate to 60% of the ability of wild-type p53. Bot h mutant proteins had reduced ability to bind to MDM2, p53 337 Arg to Cys being more reduced than p53 344 Leu to Pro. These results indicate that point mutations in the oligomerization domain can disrupt p53 fu nction. In addition, the value of LFS and LFL families for the further understanding of the biological and biochemical properties of p53 is demonstrated.