BRCA1-mediated ubiquitination inhibits topoisomerase II alpha activity in response to oxidative stress.
BRCA1-mediated ubiquitination inhibits topoisomerase II alpha activity in response to oxidative stress.
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DOI：
10.1089/ars.2007.1851
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发表时间：
2008-02
影响因子：
6.6
通讯作者：
Hirokuni Shinagawa;Y. Miki;K. Yoshida
中科院分区：
文献类型：
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作者：
Hirokuni Shinagawa;Y. Miki;K. Yoshida
拓扑异构酶iα被认为在细胞增殖和细胞死亡中起关键作用。然而，导致压力依赖性拓扑异构酶ⅱα改变的机制尚不清楚。本研究的重点是拓扑异构酶iα在过氧化氢(H（2)O(2)）诱导的氧化应激中的行为。H(2)O(2)处理后的MOLT-4细胞拓扑异构酶iα的催化活性随着拓扑异构酶iα表达的改变而下降。拓扑异构酶ⅱα的泛素化依赖于氧化应激。BRCA1，一种肿瘤抑制基因，似乎参与了拓扑异构酶ii α的这些改变。此外，BRCA1的拓扑异构酶ii α泛素化需要视网膜母细胞瘤蛋白（pRb）。我们得出结论，拓扑异构酶ii α的功能受到氧化应激时泛素化的调节。
Topoisomerase IIalpha is known to be critically involved in both cell proliferation and cell death. The mechanisms responsible for stress-dependent topoisomerase IIalpha alterations, however, remain unclear. This study focused on the behavior of topoisomerase IIalpha in response to oxidative stress induced by hydrogen peroxide (H(2)O(2)). The catalytic activity of topoisomerase IIalpha in MOLT-4 cells treated with H(2)O(2) decreased in parallel with the alteration of topoisomerase IIalpha expression. The ubiquitination of topoisomerase IIalpha was dependent on oxidative stress. BRCA1, a tumor-suppressor gene, appeared to be involved in these alterations in topoisomerase IIalpha. Furthermore, the retinoblastoma protein (pRb) was required for the ubiquitination of topoisomerase IIalpha by BRCA1. We conclude that the functions of topoisomerase IIalpha are regulated by ubiquitination on exposure to oxidative stress.