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MDM2 promotes the proteasomal degradation of p73 through the interaction with Itch in HeLa cells

Natsumi Kubo1, Rintaro Okoshi, Kumiko Nakashima

  • 1Laboratory of Anti-tumor Research, Chiba Cancer Center Research Institute, Chiba 260-8717, Japan.

Biochemical and Biophysical Research Communications
|November 25, 2010
PubMed

Insights

MDM2 targets the tumor suppressor p73 for degradation indirectly via Itch. This interaction, observed in HeLa cells, reveals a novel mechanism controlling p73 stability during apoptosis and cancer research.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Cancer Research

Background:

  • MDM2 is known to inhibit p73's transcriptional and pro-apoptotic functions.
  • Previous understanding did not include MDM2's role in p73's proteasomal degradation.

Purpose of the Study:

  • To investigate the mechanism by which MDM2 affects p73 stability.
  • To explore the role of Itch in the MDM2-p73 interaction.

Main Methods:

  • Utilized HeLa and H1299 cell lines.
  • Employed siRNA-mediated knockdown of Itch.
  • Applied proteasome inhibitor MG-132.
  • Performed co-immunoprecipitation to assess protein interactions.

Main Results:

  • MDM2 indirectly induces p73 degradation through interaction with Itch in HeLa cells.
  • MDM2 and Itch levels decreased during adriamycin-induced apoptosis, correlating with p53 and p73 stabilization.
  • Knockdown of Itch attenuated MDM2's negative impact on p73.
  • MDM2 directly bound to Itch specifically in HeLa cells.

Conclusions:

  • MDM2 promotes Itch-mediated degradation of p73.
  • This interaction is cell-type specific and occurs in HeLa cells.
  • MDM2 influences p73 stability through a novel indirect pathway involving Itch.

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