The gain of function of the p53 mutant Asp281Gly is dependent on its ability to form tetramers

The influence of tetramerisation on the properties of the p53 mutants is poorly understood. We describe here the influence of the tetramerisation on the properties of the oncogenic mutant Asp281Gly. We show that despite being both nuclear the tetrameric Asp281Gly and the monomeric Asp281GlyLeu344Pro proteins have different properties: only Asp281Gly stimulates the transcription of the multidrug resistance-1 gene promoter and induces cisplatin resistance in Saos-2 cells. Moreover, we identify a 130-kDa protein that specifically interacts with Asp281Gly but not with Asp281GlyLeu344Pro. This suggests that tetramerisation is important for the properties of the p53 mutants and that these properties might be mediated via protein-protein interactions.