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 p
romotes p53 degradation through a ubiquitin-dependent pathway on 26S protea
somes and is thought to be largely responsible for the very low levels of p
53 protein in unstressed cells. The rationale for targeting the p53-mdm2 in
teraction therapeutically lies in the ability to activate p53 in all those
tumors that retain wild type p53. (C) 2900 Harcourt Publishers Ltd.