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Tumour suppressor TRIM33 targets nuclear β-catenin degradation

Jianfei Xue1, Yaohui Chen1, Yamei Wu1

  • 1Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.

Nature Communications
|February 3, 2015
PubMed

Insights

Tripartite motif-containing protein 33 (TRIM33) degrades nuclear beta-catenin, suppressing cancer cell proliferation. This discovery offers a new therapeutic strategy for beta-catenin-driven cancers.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Aberrant nuclear beta-catenin activation is a hallmark of many human cancers.
  • The mechanisms regulating nuclear beta-catenin stability and degradation remain largely unknown.

Purpose of the Study:

  • To investigate the role of tripartite motif-containing protein 33 (TRIM33) in regulating nuclear beta-catenin.
  • To elucidate the mechanism by which TRIM33 affects beta-catenin stability and its implications in cancer.

Main Methods:

  • Investigated TRIM33's function as an E3 ubiquitin ligase targeting nuclear beta-catenin.
  • Utilized co-immunoprecipitation and ubiquitination assays to study TRIM33-beta-catenin interaction.
  • Examined the role of protein kinase Cδ in the TRIM33-beta-catenin interaction.
  • Assessed TRIM33's effect on tumor cell proliferation and glioblastoma development.
  • Correlated TRIM33 and beta-catenin levels in human glioblastoma specimens.

Main Results:

  • TRIM33 reduces nuclear beta-catenin abundance by acting as an E3 ubiquitin ligase.
  • TRIM33-mediated beta-catenin degradation is independent of GSK-3β or β-TrCP.
  • Protein kinase Cδ phosphorylation of beta-catenin at Ser715 is crucial for TRIM33 interaction.
  • TRIM33 suppresses tumor cell proliferation and brain tumor development by promoting beta-catenin degradation.
  • Endogenous TRIM33 levels are inversely correlated with beta-catenin in human glioblastoma.

Conclusions:

  • TRIM33 functions as a tumor suppressor by degrading nuclear beta-catenin.
  • TRIM33 inhibits tumor cell proliferation and tumorigenesis.
  • TRIM33 represents a potential therapeutic target for beta-catenin-driven cancers.

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