title: Tumour suppressor TRIM33 targets nuclear β-catenin degradation.
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.
authors: Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors: Jianfei
authors: J
authors: Xue
authors: Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors: Yaohui
authors: Y
authors: Chen
authors: Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors: Yamei
authors: Y
authors: Wu
authors: Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors: Zhongyong
authors: Z
authors: Wang
authors: Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors: Aidong
authors: A
authors: Zhou
authors: 1] Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA [2] Program in Cancer Biology, The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, Texas 77030, USA.
authors: Sicong
authors: S
authors: Zhang
authors: Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors: Kangyu
authors: K
authors: Lin
authors: Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors: Kenneth
authors: K
authors: Aldape
authors: 1] Program in Cancer Biology, The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, Texas 77030, USA [2] Department of Genetics, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors: Sadhan
authors: S
authors: Majumder
authors: 1] Program in Cancer Biology, The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, Texas 77030, USA [2] Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors: Zhimin
authors: Z
authors: Lu
authors: 1] Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA [2] Program in Cancer Biology, The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, Texas 77030, USA.
authors: Suyun
authors: S
authors: Huang
mesh_terms: D000818:Animals; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D006801:Humans; D051379:Mice; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D054875:Ubiquitination; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
chemical_list: C511956:TRIM33 protein, human; D014157:Transcription Factors; D051176:beta Catenin
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