Tumour suppressor OTUD3 induces growth inhibition and apoptosis by directly deubiquitinating and stabilizing p53 in invasive breast carcinoma cells

Abstract

Background P53 pathway inactivation plays an important role in the process of breast cancer tumourigenesis. Post-translational protein modification abnormalities have been confirmed to be an important mechanism underlying the inactivation of p53. Numerous deubiquitinating enzymes are aberrantly expressed in breast cancer, and a few deubiquitination enzymes are capable of deubiquitinating and stabilizing p53. Here, we report that OTUD3 is a deubiquitylase of p53 in breast carcinoma.Methods The correlation between the mRNA expression of OTUD3, TP53 and PTEN and the prognosis of BC was assessed with the Kaplan-Meier Plotter tool. OTUD3 protein expression in breast carcinoma was examined by immunohistochemistry and western blotting. The relationship among OTUD3, p53, and p21 proteins was analysed. Half-life analysis and ubiquitylation assay were performed to elucidate the molecular mechanism by which OTUD3 stabilizes p53. The interaction between OTUD3 and p53 in BC cells was verified by a co-immunoprecipitation assay and GST pulldown experiments.MTS proliferation detection, an apoptosis detection kit and colony formation asssy were used to investigate the functional effects of OTUD3 on breast cancer cells.