BRCA1-Mediated Ubiquitination Inhibits Topoisomerase II α Activity in Response to Oxidative Stress

Abstract

Topoisomerase IIα is known to be critically involved in both cell proliferation and cell death. The mechanisms responsible for stress-dependent topoisomerase IIα alterations, however, remain unclear. This study focused on the behavior of topoisomerase IIα in response to oxidative stress induced by hydrogen peroxide (H₂O₂). The catalytic activity of topoisomerase IIα in MOLT-4 cells treated with H₂O₂ decreased in parallel with the alteration of topoisomerase IIα expression. The ubiquitination of topoisomerase IIα was dependent on oxidative stress. BRCA1, a tumor-suppressor gene, appeared to be involved in these alterations in topoisomerase IIα. Furthermore, the retinoblastoma protein (pRb) was required for the ubiquitination of topoisomerase IIα by BRCA1. We conclude that the functions of topoisomerase IIα are regulated by ubiquitination on exposure to oxidative stress.