Elsevier

Experimental Cell Research

Volume 255, Issue 1, 25 February 2000, Pages 86-94
Experimental Cell Research

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

https://doi.org/10.1006/excr.1999.4772Get rights and content

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.

References (56)

  • C.A. Austin et al.

    Expression, domain structure, and enzymatic properties of an active recombinant human DNA topoisomerase IIβ

    J. Biol. Chem.

    (1995)
  • S.E. Mirski et al.

    Bipartite nuclear localization signals in the C terminus of human topoisomerase IIα

    Exp. Cell Res.

    (1997)
  • J.C. Wang

    DNA topoisomerases

    Annu. Rev. Biochem.

    (1996)
  • P.R. Caron et al.
  • F.H. Drake et al.

    Biochemical and pharmacological properties of p170 and p180 forms of topoisomerase II

    Biochemistry (USA)

    (1989)
  • T.D.Y. Chung et al.

    Characterization and immunological identification of cDNA clones encoding two human DNA topoisomerase II isoenzymes

    Proc. Natl. Acad. Sci. USA

    (1989)
  • M. Tsai Pflugfelder et al.

    Cloning and sequencing of cDNA encoding human DNA topoisomerase II and localization of the gene to chromosome region 17q21–22

    Proc. Natl. Acad. Sci. USA

    (1988)
  • S.L. Davies et al.

    Human cells express two differentially spliced forms of topoisomerase IIβ mRNA

    Nucleic Acids Res.

    (1993)
  • J.R. Jenkins et al.

    Isolation of cDNA clones encoding the beta isozyme of human DNA topoisomerase II and localisation of the gene to chromosome 3p24

    Nucleic Acids Res.

    (1992)
  • E. Willmore et al.

    Etoposide targets topoisomerase IIα and IIβ in leukemic cells: Isoform-specific cleavable complexes visualized and quantified in situ by a novel immunofluorescence technique

    Mol. Pharmacol.

    (1998)
  • S.W. Lowe et al.

    p53 status and the efficacy of cancer therapy in vivo

    Science

    (1994)
  • L.J. Ko et al.

    p53: Puzzle and paradigm

    Genes Dev.

    (1996)
  • A.L. Okorokov et al.

    Proteolytic cleavage of p53: A model for the activation of p53 in response to DNA damage

    Oncol. Res.

    (1997)
  • L.C. Huang et al.

    Sensitivity and selectivity of the DNA damage sensor responsible for activating p53-dependent G(1) arrest

    Proc. Natl. Acad. Sci. USA

    (1996)
  • L. Wu et al.

    Alternatively spliced forms in the carboxy-terminal domain of p53 protein regulate its ability to promote annealing of complementary single strands of nucleic-acids

    Mol. Cell. Biol.

    (1995)
  • Y. Li et al.

    Cell cycle expression and p53 regulation of the cyclin-dependent kinase inhibitor p21

    Oncogene

    (1994)
  • A. Di Leonardo et al.

    DNA damage triggers a prolonged p53-dependent G1 arrest and long-term induction of Cip1 in normal human fibroblasts

    Genes Dev.

    (1994)
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    1

    Current address: Division of Integrative Biology, The Roslin Institute (Edinburgh), Roslin, Midlothian EH25 9PS.

    2

    To whom correspondence and reprint requests should be addressed at School of Biochemistry and Genetics, The Medical School, University of Newcastle, Newcastle upon Tyne NE2 4HH. Fax: 0191 222 7424. E-mail: [email protected].

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