Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Cancer Cell. 2005 Jun;7(6):547-59.

Small molecule inhibitors of HDM2 ubiquitin ligase activity stabilize and activate p53 in cells.

Author information

  • 1Laboratory of Protein Dynamics and Signaling, Center for Cancer Research, National Cancer Institute at Frederick, NIH, 1050 Boyles Street, Frederick, MD 21702, USA.

Abstract

The p53 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.

PMID:
15950904
[PubMed - indexed for MEDLINE]
Free full text

MeSH Terms, Substances

MeSH Terms

Substances

PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science
    Loading ...
    Write to the Help Desk