Dataset Information


Tumour suppressor TRIM33 targets nuclear ?-catenin degradation.

ABSTRACT: Aberrant activation of ?-catenin in the nucleus has been implicated in a variety of human cancers, but the fate of nuclear ?-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 ?-catenin protein. TRIM33-mediated ?-catenin is destabilized and is GSK-3? or ?-TrCP independent. TRIM33 interacts with and ubiquitylates nuclear ?-catenin. Moreover, protein kinase C?, which directly phosphorylates ?-catenin at Ser715, is required for the TRIM33-?-catenin interaction. The function of TRIM33 in suppressing tumour cell proliferation and brain tumour development depends on TRIM33-promoted ?-catenin degradation. In human glioblastoma specimens, endogenous TRIM33 levels are inversely correlated with ?-catenin. In summary, our findings identify TRIM33 as a tumour suppressor that can abolish tumour cell proliferation and tumorigenesis by degrading nuclear ?-catenin. This work suggests a new therapeutic strategy against human cancers caused by aberrant activation of ?-catenin.


PROVIDER: S-EPMC4315364 | BioStudies | 2015-01-01

REPOSITORIES: biostudies

Similar Datasets

2008-01-01 | S-EPMC2830866 | BioStudies
2020-01-01 | S-EPMC7468622 | BioStudies
2017-01-01 | S-EPMC5524345 | BioStudies
2019-01-01 | S-EPMC6547372 | BioStudies
2017-01-01 | S-EPMC5650645 | BioStudies
2017-01-01 | S-EPMC5354896 | BioStudies
2019-01-01 | S-EPMC6721565 | BioStudies
2019-01-01 | S-EPMC6604767 | BioStudies
2019-01-01 | S-EPMC6594006 | BioStudies
2019-01-01 | S-EPMC6898130 | BioStudies