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. Copyright 2000 Harcourt Publishers Ltd.
Moll
Ute M.
UM
Department of Pathology, State University of New York at Stony Brook, Stony Brook, NY, 11794-8691, USA
Zaika
Alex
A