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Updated: May 19, 2026

Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs
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Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs

Published on: May 15, 2019

TRIAD1 is negatively regulated by the MDM2 E3 ligase

Seunghee Bae1, Jin Hyuk Jung, In-Sook An

  • 1Molecular-Targeted Drug Research Center, Konkuk University, Gwangjin-gu, Seoul 143-701, Republic of Korea.

Oncology Reports
|September 4, 2012
PubMed

Insights

The protein TRIAD1, which promotes apoptosis and p53 activation, is degraded by MDM2. This MDM2-mediated degradation of TRIAD1 (Two RING fingers and DRIL1) suppresses cancer cell growth.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cellular Biology

Background:

  • Two RING fingers and DRIL1 (TRIAD1) is a proapoptotic protein.
  • TRIAD1 promotes p53 activation in various cancer cell lines.
  • Understanding TRIAD1 regulation is crucial for cancer therapy.

Purpose of the Study:

  • To investigate the regulatory mechanism of TRIAD1 protein.
  • To identify proteins that ubiquitinate TRIAD1.
  • To elucidate the role of TRIAD1 degradation in cancer cell growth.

Main Methods:

  • Co-immunoprecipitation to study protein interactions.
  • Western blotting to detect protein levels and ubiquitination.
  • RNA interference to deplete MDM2 levels.
  • Cell viability assays to assess cell growth.

Main Results:

  • TRIAD1 interacts with and is ubiquitinated by murine double minute 2 (MDM2).
  • MDM2 targets TRIAD1 for proteasome-dependent degradation.
  • Knockdown of MDM2 enhances the stability of endogenous TRIAD1 protein.
  • Degradation of TRIAD1 by MDM2 inhibits TRIAD1-mediated cell growth suppression.

Conclusions:

  • MDM2 acts as an E3 ligase, ubiquinating TRIAD1 for degradation.
  • This represents a novel negative regulatory pathway for TRIAD1.
  • MDM2-mediated TRIAD1 degradation plays a role in suppressing cancer cell proliferation.

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