BRCA1-mediated ubiquitination inhibits topoisomerase IIα activity in response to oxidative stress

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