Nature Communications (Apr 2020)

Structural basis for DNA damage-induced phosphoregulation of MDM2 RING domain

  • Helge M. Magnussen,
  • Syed F. Ahmed,
  • Gary. J. Sibbet,
  • Ventzislava A. Hristova,
  • Koji Nomura,
  • Andreas K. Hock,
  • Lewis J. Archibald,
  • Andrew G. Jamieson,
  • David Fushman,
  • Karen H. Vousden,
  • Allan M. Weissman,
  • Danny T. Huang

DOI
https://doi.org/10.1038/s41467-020-15783-y
Journal volume & issue
Vol. 11, no. 1
pp. 1 – 15

Abstract

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p53 is an important tumor suppressor protein which is regulated by the E3 ubiquitin ligase MDM2. Here the authors reveal that DNA damage-induced Ser429 phosphorylation of MDM2 serve to boost the activity of MDM2 homodimer by stabilizing the active E2–ubiquitin complex and promote its self-destruction to enable rapid p53 stabilization.