Interactions of the Hdm2/p53 and proteasome pathways may enhance the antitumor activity of bortezomib.
Title | Interactions of the Hdm2/p53 and proteasome pathways may enhance the antitumor activity of bortezomib. |
Publication Type | Journal Article |
Year of Publication | 2009 |
Authors | Ooi, M. G., Hayden P. J., Kotoula V., McMillin D. W., Charalambous E., Daskalaki E., Raje N. S., Munshi N. C., Chauhan D., Hideshima T., Buon L., Clynes M., O'Gorman P., Richardson P. G., Mitsiades C. S., Anderson K. C., & Mitsiades N. |
Journal | Clin Cancer Res |
Volume | 15 |
Issue | 23 |
Pagination | 7153-60 |
Date Published | 2009 Dec 01 |
ISSN | 1078-0432 |
Keywords | Antineoplastic Agents, Apoptosis, Boronic Acids, Bortezomib, Breast Neoplasms, Carcinoma, Cell Line, Tumor, Cell Survival, Humans, Imidazoles, Multiple Myeloma, Mutation, Missense, Neoplasms, Glandular and Epithelial, Piperazines, Proteasome Endopeptidase Complex, Proteasome Inhibitors, Proto-Oncogene Proteins c-mdm2, Pyrazines, Tumor Suppressor Protein p53 |
Abstract | PURPOSE: p53 is inactivated in many human malignancies through missense mutations or overexpression of the human homologue of Mdm2 (Hdm2), an E3 ubiquitin ligase that ubiquitinates p53, thereby promoting its proteasomal degradation. The cis-imidazoline nutlin-3 can disrupt the p53-Hdm2 interaction and activate p53, inducing apoptosis in vitro in many malignancies, including multiple myeloma (MM). |
DOI | 10.1158/1078-0432.CCR-09-1071 |
Alternate Journal | Clin Cancer Res |
PubMed ID | 19934289 |
PubMed Central ID | PMC3672410 |
Grant List | R01 CA050947 / CA / NCI NIH HHS / United States R01 CA050947-17A1 / CA / NCI NIH HHS / United States |