Human Topoisomerase IIα and IIβ Interact with the C-Terminal Region of p53

Ian G. Cowell, Andrei L. Okorokov, Sarah A. Cutts, Kay Padget, Margaret Bell, Jo Milner, Caroline A. Austin

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    57 Citations (Scopus)

    Abstract

    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 IIβ has previously been shown to interact with p53, and we have extended this analysis to show that both topo IIα and IIβ 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.
    Original languageEnglish
    Pages (from-to)86-94
    JournalExperimental Cell Research
    Volume255
    Issue number1
    DOIs
    Publication statusPublished - 25 Feb 2000

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