Human topoisomerase IIα and IIβ interact with the C-terminal region of p53

被引:54
作者
Cowell, IG
Okorokov, AL
Cutts, SA
Padget, K
Bell, M
Milner, J
Austin, CA [1 ]
机构
[1] Newcastle Univ, Sch Med, Sch Biochem & Genet, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England
[2] Univ York, Dept Biol, YCR p53 Res Grp, York YO1 5DD, N Yorkshire, England
关键词
topoisomerase; p53; DNA repair; tumor suppressor; DNA damage;
D O I
10.1006/excr.1999.4772
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The p53 tumor suppressor protein is a critical regulator of cell cycle progression and apoptosis following exposure of cells to DNA damaging agents such as ionizing radiation or anticancer drugs. An important group of anticancer drugs, including compounds such as etoposide and doxorubicin (Adriamycin), interacts with DNA topoisomerase II (topo II), causing the accumulation of enzyme-DNA adducts that ultimately lead to double-strand breaks and cell death via apoptosis. Human topo II beta has previously been shown to interact with p53, and we have extended this analysis to show that both topo II alpha and II beta interact with p53 in vivo and in vitro. Furthermore, we show that the regulatory C-terminal basic region of p53 (residues 364-393) is necessary and sufficient for interaction with DNA topo II. (C) 2000 Academic Press.
引用
收藏
页码:86 / 94
页数:9
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