Yang, Y. et al. (2005) Small molecule inhibitors of HDM2 ubiquitin ligase activity stabilize and activate p53 in cells. Cancer Cell, 7(6), pp. 547-559. (doi: 10.1016/j.ccr.2005.04.029)
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Abstract
The p53 tumor suppressor protein is regulated by its interaction with Ill which serves as a ubiquitin ligase (E3) to target p53 for degradation. We have identified a family of small molecules (HL198) 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.
Item Type: | Articles |
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Status: | Published |
Refereed: | Yes |
Glasgow Author(s) Enlighten ID: | Vousden, Karen |
Authors: | Yang, Y., Ludwig, R., Jensen, J., Pierre, S., Medaglia, M., Davydov, I., Safiran, Y., Oberoi, P., Kenten, J., Phillips, A., Weissman, A., and Vousden, K. |
College/School: | College of Medical Veterinary and Life Sciences > School of Cancer Sciences |
Journal Name: | Cancer Cell |
ISSN: | 1535-6108 |
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