Oncogenic Mutation of AIMP2/p38 Inhibits Its Tumor-Suppressive Interaction with Smurf2

Dae Gyu Kim1, Jin Young Lee1, Ji-Hyun Lee1

  • 1Medicinal Bioconvergence Research Center, College of Pharmacy, Seoul National University, Seoul, Korea.

Cancer Research
|May 20, 2016
PubMed

Insights

A novel tumor suppressor interaction between AIMP2 and Smurf2 was discovered. Disruption of this interaction promotes cellular transformation and tumorigenesis, highlighting a new pathway in cancer development.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cellular Biology

Background:

  • AIMP2/p38 acts as a tumor suppressor by degrading FUSE-binding protein (FBP), a c-Myc activator.
  • The precise mechanism of AIMP2's tumor-suppressive function and its role in tumorigenesis remain unclear.

Purpose of the Study:

  • To elucidate the mechanism of AIMP2-mediated FBP degradation.
  • To investigate the interaction between AIMP2 and Smurf2 in tumor suppression.
  • To determine the significance of this interaction in tumorigenesis.

Main Methods:

  • Investigated the role of Smurf2 in AIMP2-mediated ubiquitination of FBP.
  • Analyzed the effect of AIMP2 mutations on cellular transformation and in vivo tumorigenesis.
  • Examined the impact of TGFβ treatment on AIMP2 phosphorylation and localization.
  • Studied the interaction between phosphorylated AIMP2 and Smurf2 in the nucleus.

Main Results:

  • Smurf2 mediates AIMP2-induced ubiquitination and degradation of FBP.
  • A mutation preventing AIMP2-Smurf2 nuclear interaction increased tumorigenesis.
  • TGFβ induced AIMP2 phosphorylation at S156, causing nuclear translocation and Smurf2 binding.
  • Phospho-AIMP2 enhanced FBP ubiquitination and inhibited Smurf2 nuclear export, sustaining TGFβ signaling.

Conclusions:

  • A novel tumor-suppressive pathway involving AIMP2 and Smurf2 has been identified.
  • The AIMP2-Smurf2 interaction is crucial for suppressing FBP-mediated oncogenic transformation.
  • Disruption of this interaction contributes to tumorigenesis, offering potential therapeutic targets.

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