Oncoprotein MDM2 is a ubiquitin ligase E3 for tumor suppressor p53

Authors

  • Reiko Honda,

    1. School of Life Science, Tokyo University of Pharmacy and Life Science, Hachioji, 1432-1 Horinouchi, Tokyo 192-03, Japan
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  • Hirofumi Tanaka,

    1. School of Life Science, Tokyo University of Pharmacy and Life Science, Hachioji, 1432-1 Horinouchi, Tokyo 192-03, Japan
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  • Hideyo Yasuda

    Corresponding author
    1. School of Life Science, Tokyo University of Pharmacy and Life Science, Hachioji, 1432-1 Horinouchi, Tokyo 192-03, Japan
    • Corresponding author. Fax: +81 (426) 76-7249. E-mail: yasuda@ls.toyaku.ac.jp

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Abstract

The tumor suppressor p53 is degraded by the ubiquitin-proteasome system. p53 was polyubiquitinated in the presence of E1, UbcH5 as E2 and MDM2 oncoprotein. A ubiquitin molecule bound MDM2 through sulfhydroxy bond which is characteristic of ubiquitin ligase (E3)-ubiquitin binding. The cysteine residue in the carboxyl terminus of MDM2 was essential for the activity. These data suggest that the MDM2 protein, which is induced by p53, functions as a ubiquitin ligase, E3, in human papillomavirus-uninfected cells which do not have E6 protein.

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