Alternariol induces DNA polymerase β expression through the PKA-CREB signaling pathway

  • Authors:
    • Jimin Zhao
    • Kangdong Liu
    • Jing Lu
    • Junfen Ma
    • Xiaoyan Zhang
    • Yanan Jiang
    • Hongyan Yang
    • Ge Jin
    • Guoqiang Zhao
    • Mingyao Zhao
    • Ziming Dong
  • View Affiliations

  • Published online on: March 8, 2012     https://doi.org/10.3892/ijo.2012.1398
  • Pages: 1923-1928
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Abstract

Alternariol (AOH) is a mycotoxin of Alternaria alternata and can cause DNA damage and gene mutations. Low-dose and long-term treatment with AOH has been linked with incidence of esophageal carcinoma. DNA polymerase β (polβ) is a key enzyme in DNA base excision repair (BER). When it is overexpressed or mutated in cells, DNA polβ can cause genetic instability. Elevated DNA polβ has also been reported in several human cancers. Here, we report that AOH at 2, 10, 20 µM induces DNA polβ expression. In the process, protein kinase A (PKA) catalytic subunit activation, nuclear translocation and cAMP response element binding protein (CREB) phosphorylation are involved. AOH also increased CREB binding to the cAMP response element (CRE) consensus motif, which is present in the DNA polβ gene promoter. The PKA inhibitor H89 was able to block AOH-induced PKA-CREB activation, CREB DNA binding activity and decrease DNA polβ expression. Our results suggest that AOH can upregulate DNA polβ expression through the PKA-CREB signal transduction pathway.

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June 2012
Volume 40 Issue 6

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Zhao J, Liu K, Lu J, Ma J, Zhang X, Jiang Y, Yang H, Jin G, Zhao G, Zhao M, Zhao M, et al: Alternariol induces DNA polymerase β expression through the PKA-CREB signaling pathway. Int J Oncol 40: 1923-1928, 2012.
APA
Zhao, J., Liu, K., Lu, J., Ma, J., Zhang, X., Jiang, Y. ... Dong, Z. (2012). Alternariol induces DNA polymerase β expression through the PKA-CREB signaling pathway. International Journal of Oncology, 40, 1923-1928. https://doi.org/10.3892/ijo.2012.1398
MLA
Zhao, J., Liu, K., Lu, J., Ma, J., Zhang, X., Jiang, Y., Yang, H., Jin, G., Zhao, G., Zhao, M., Dong, Z."Alternariol induces DNA polymerase β expression through the PKA-CREB signaling pathway". International Journal of Oncology 40.6 (2012): 1923-1928.
Chicago
Zhao, J., Liu, K., Lu, J., Ma, J., Zhang, X., Jiang, Y., Yang, H., Jin, G., Zhao, G., Zhao, M., Dong, Z."Alternariol induces DNA polymerase β expression through the PKA-CREB signaling pathway". International Journal of Oncology 40, no. 6 (2012): 1923-1928. https://doi.org/10.3892/ijo.2012.1398