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

doi:10.1006/excr.1999.4772

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

Applied Sciences Department

Research output: Contribution to journal › Article › peer-review

55 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 language	English
Pages (from-to)	86-94
Journal	Experimental Cell Research
Volume	255
Issue number	1
DOIs	https://doi.org/10.1006/excr.1999.4772
Publication status	Published - 25 Feb 2000

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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.",

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AU - Cowell, Ian G.

AU - Okorokov, Andrei L.

AU - Cutts, Sarah A.

AU - Padget, Kay

AU - Bell, Margaret

AU - Milner, Jo

AU - Austin, Caroline A.

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AB - 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.

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DO - 10.1006/excr.1999.4772

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VL - 255

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JO - Experimental Cell Research

JF - Experimental Cell Research

IS - 1

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

Abstract

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