APE1/Ref-1 enhances DNA binding activity of mutant p53 in a redox-dependent manner

  • Authors:
    • Yanping Cun
    • Nan Dai
    • Mengxia Li
    • Chengjie Xiong
    • Qinhong Zhang
    • Jiangdong Sui
    • Chengyuan Qian
    • Dong Wang
  • View Affiliations

  • Published online on: December 2, 2013     https://doi.org/10.3892/or.2013.2892
  • Pages: 901-909
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Abstract

Apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/Ref-1) is a dual function protein; in addition to its DNA repair activity, it can stimulate DNA binding activity of numerous transcription factors as a reduction-oxidation (redox) factor. APE1/Ref-1 has been found to be a potent activator of wild-type p53 (wtp53) DNA binding in vitro and in vivo. Although p53 is mutated in most types of human cancer including hepatocellular carcinoma (HCC), little is known about whether APE1/Ref-1 can regulate mutant p53 (mutp53). Herein, we reported the increased APE1/Ref-1 protein and accumulation of mutp53 in HCC by immunohistochemistry. Of note, it was observed that APE1/Ref-1 high-expression and mutp53 expression were associated with carcinogenesis and progression of HCC. To determine whether APE1/Ref-1 regulates DNA binding of mutp53, we performed electromobility shift assays (EMSAs) and quantitative chromatin immunoprecipitation (ChIP) assays in HCC cell lines. In contrast to sequence-specific and DNA structure-dependent binding of wtp53, reduced mutp53 efficiently bound to nonlinear DNA, but not to linear DNA. Notably, overexpression of APE1/Ref-1 resulted in increased DNA binding activity of mutp53, while downregulation of APE1/Ref-1 caused a marked decrease of mutp53 DNA binding. In addition, APE1/Ref-1 could not potentiate the accumulation of p21 mRNA and protein in mutp53 cells. These data indicate that APE1/Ref-1 can stimulate mutp53 DNA binding in a redox-dependent manner.
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2014-February
Volume 31 Issue 2

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Cun Y, Dai N, Li M, Xiong C, Zhang Q, Sui J, Qian C and Wang D: APE1/Ref-1 enhances DNA binding activity of mutant p53 in a redox-dependent manner. Oncol Rep 31: 901-909, 2014
APA
Cun, Y., Dai, N., Li, M., Xiong, C., Zhang, Q., Sui, J. ... Wang, D. (2014). APE1/Ref-1 enhances DNA binding activity of mutant p53 in a redox-dependent manner. Oncology Reports, 31, 901-909. https://doi.org/10.3892/or.2013.2892
MLA
Cun, Y., Dai, N., Li, M., Xiong, C., Zhang, Q., Sui, J., Qian, C., Wang, D."APE1/Ref-1 enhances DNA binding activity of mutant p53 in a redox-dependent manner". Oncology Reports 31.2 (2014): 901-909.
Chicago
Cun, Y., Dai, N., Li, M., Xiong, C., Zhang, Q., Sui, J., Qian, C., Wang, D."APE1/Ref-1 enhances DNA binding activity of mutant p53 in a redox-dependent manner". Oncology Reports 31, no. 2 (2014): 901-909. https://doi.org/10.3892/or.2013.2892