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Mdmx enhances p53 ubiquitination by altering the substrate preference of the Mdm2 ubiquitin ligase |
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| Authors: | Koji Okamoto Yoichi Taya Hitoshi Nakagama |
| Institution: | a National Cancer Center Research Institute, Early Oncogenesis Research Project, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan b National Cancer Center Research Institute, Radiobiology Division, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan c SORST, Japan Science and Technology Corporation, Japan |
| Abstract: | mdm2 and mdmx oncogenes play essential yet non-redundant roles in synergistic inactivation of the tumor suppressor, p53. While Mdm2 inhibits p53 activity mainly by augmenting its ubiquitination, the functional role of Mdmx on p53 ubiquitination remains obscure. In transfected H1299 cells, Mdmx augmented Mdm2-mediated ubiquitination of p53. In in vitro ubiquitination assays, the Mdmx/Mdm2 heteromeric complex, in comparison to the Mdm2 homomer, showed enhanced ubiquitinase activity toward p53 and the reduced auto-ubiquitination of Mdm2. Alteration of the substrate specificity via binding to Mdmx may contribute to efficient ubiquitination and inactivation of p53 by Mdm2.Structured summaryMINT-7219995: P53 (uniprotkb:P04637) physically interacts (MI:0914) with Ubiquitin (uniprotkb:P62988) by anti bait coimmunoprecipitation (MI:0006)MINT-7220023: Ubiquitin (uniprotkb:P62988) physically interacts (MI:0914) with P53 (uniprotkb:P04637) by pull down (MI:0096) |
| Keywords: | Mdmx Mdm2 p53 Ubiquitination |
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