FEBS Letters
Volume 583, Issue 17 , Pages 2710-2714, 3 September 2009

Mdmx enhances p53 ubiquitination by altering the substrate preference of the Mdm2 ubiquitin ligase

Edited by Noboru Mizushima

  • Koji Okamoto

      Affiliations

    • National Cancer Center Research Institute, Early Oncogenesis Research Project, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan
    • National Cancer Center Research Institute, Radiobiology Division, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan
    • SORST, Japan Science and Technology Corporation, Japan
    • ,
  • Yoichi Taya

      Affiliations

    • National Cancer Center Research Institute, Radiobiology Division, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan
    • SORST, Japan Science and Technology Corporation, Japan
    • Present address: Cancer Science Institute of Singapore, National University of Singapore, Singapore 117456, Singapore.
    • ,
  • Hitoshi Nakagama

      Affiliations

    • National Cancer Center Research Institute, Early Oncogenesis Research Project, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan
    • Corresponding Author InformationCorresponding author.

Received 11 May 2009; received in revised form 26 June 2009; accepted 13 July 2009. published online 20 July 2009.

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 summary

MINT-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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PII: S0014-5793(09)00551-1

doi:10.1016/j.febslet.2009.07.021

FEBS Letters
Volume 583, Issue 17 , Pages 2710-2714, 3 September 2009

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