Tumour suppressor TRIM33 targets nuclear β-catenin degradation

Nat Commun. 2015 Feb 2;6:6156. doi: 10.1038/ncomms7156.


Aberrant activation of β-catenin in the nucleus has been implicated in a variety of human cancers, but the fate of nuclear β-catenin is unknown. Here we demonstrate that the tripartite motif-containing protein 33 (TRIM33), acting as an E3 ubiquitin ligase, reduces the abundance of nuclear β-catenin protein. TRIM33-mediated β-catenin is destabilized and is GSK-3β or β-TrCP independent. TRIM33 interacts with and ubiquitylates nuclear β-catenin. Moreover, protein kinase Cδ, which directly phosphorylates β-catenin at Ser715, is required for the TRIM33-β-catenin interaction. The function of TRIM33 in suppressing tumour cell proliferation and brain tumour development depends on TRIM33-promoted β-catenin degradation. In human glioblastoma specimens, endogenous TRIM33 levels are inversely correlated with β-catenin. In summary, our findings identify TRIM33 as a tumour suppressor that can abolish tumour cell proliferation and tumorigenesis by degrading nuclear β-catenin. This work suggests a new therapeutic strategy against human cancers caused by aberrant activation of β-catenin.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Line
  • Cell Line, Tumor
  • Cell Proliferation
  • Humans
  • Mice
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Ubiquitination
  • beta Catenin / genetics
  • beta Catenin / metabolism*


  • TRIM33 protein, human
  • Transcription Factors
  • beta Catenin