Disrupting the p53-mdm2 interaction as a potential therapeutic modality

P53 and mdm2 are linked to each other through a negative feedback loop. P53 transactivates mdm2, but mdm2, in turn, is a major opponent of p53. Mdm2 promotes p53 degradation through a ubiquitin-dependent pathway on 26S proteasomes and is thought to be largely responsible for the very low levels of p53 protein in unstressed cells. The rationale for targeting the p53-mdm2 interaction therapeutically lies in the ability to activate p53 in all those tumors that retain wild type p53. (C) 2000 Harcourt Publishers Ltd.