Characterisation of the BRCT/DBL Protein ECT2 in cell cycle regulation

Abstract

Ect2 is a member of the Dbl family of proto-oncogenes and exhibits exchange activity for Rho-GTPases. It is over-expressed in dividing cells and tumours such as gliomas, although its role in oncogenesis is not clear. Firstly in this study, we demonstrate that Ect2 has a role in cell cycle regulation in human glioma cells. Ect2 promotes G1/S transition by modulating the levels of CDK inhibitor p27Kip1 through mRNA stability and protein degradation, as well as Rb phosphorylation. This is achieved by the exchange activity of Ect2 on RhoA GTPase. Secondly, we show that suppression of Ect2 reduces viability of chemo- and radio-resistant human glioma cells in vitro. Taken together, these results validate the use of Ect2 as a biomarker for accurate glioma grading, as well as forming the basis for Ect2 as a candidate for targeted therapy in glioma treatment.