Tumour suppressor TRIM33 targets nuclear β-catenin degradation

Jianfei Xue, Yaohui Chen, Yamei Wu, Zhongyong Wang, Aidong Zhou, Sicong Zhang, Kangyu Lin, Kenneth Aldape, Sadhan Majumder, Zhimin Lu and Suyun Huang ()
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Jianfei Xue: The University of Texas MD Anderson Cancer Center
Yaohui Chen: The University of Texas MD Anderson Cancer Center
Yamei Wu: The University of Texas MD Anderson Cancer Center
Zhongyong Wang: The University of Texas MD Anderson Cancer Center
Aidong Zhou: The University of Texas MD Anderson Cancer Center
Sicong Zhang: The University of Texas MD Anderson Cancer Center
Kangyu Lin: The University of Texas MD Anderson Cancer Center
Kenneth Aldape: The University of Texas MD Anderson Cancer Center
Sadhan Majumder: Program in Cancer Biology, The University of Texas Graduate School of Biomedical Sciences at Houston
Zhimin Lu: Program in Cancer Biology, The University of Texas Graduate School of Biomedical Sciences at Houston
Suyun Huang: The University of Texas MD Anderson Cancer Center

Nature Communications, 2015, vol. 6, issue 1, 1-16

Abstract: Abstract 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.

Date: 2015
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DOI: 10.1038/ncomms7156

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