Author/Authors :
Yang، نويسنده , , Yili and Ludwig، نويسنده , , Robert L. and Jensen، نويسنده , , Jane P. and Pierre، نويسنده , , Shervon A. and Medaglia، نويسنده , , Maxine V. and Davydov، نويسنده , , Ilia V. and Safiran، نويسنده , , Yassamin J. and Oberoi، نويسنده , , Pankaj and Kenten، نويسنده , , John H. and Phillips، نويسنده , , Andrew C. and Weissman، نويسنده , , Allan M. and Vousden، نويسنده , , Karen H.، نويسنده ,
Abstract :
Summary
3 tumor suppressor protein is regulated by its interaction with HDM2, which serves as a ubiquitin ligase (E3) to target p53 for degradation. We have identified a family of small molecules (HLI98) that inhibits HDM2’s E3 activity. These compounds show some specificity for HDM2 in vitro, although at higher concentrations effects on unrelated RING and HECT domain E3s are detectable, which could be due, at least in part, to effects on E2-ubiquitin thiol-ester levels. In cells, the compounds allow the stabilization of p53 and HDM2 and activation of p53-dependent transcription and apoptosis, although other p53-independent toxicity was also observed.
