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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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Chronophin activation is necessary in Doxorubicin-induced actin cytoskeleton alteration

  • Lee, Su Jin (School of Life Science, College of Natural Science, Kyungpook National University) ;
  • Park, Jeen Woo (School of Life Science, College of Natural Science, Kyungpook National University) ;
  • Kang, Beom Sik (School of Life Science, College of Natural Science, Kyungpook National University) ;
  • Lee, Dong-Seok (School of Life Science, College of Natural Science, Kyungpook National University) ;
  • Lee, Hyun-Shik (School of Life Science, College of Natural Science, Kyungpook National University) ;
  • Choi, Sooyoung (Department of Biomedical Sciences and Research Institute for Bioscience and Biotechnology, Hallym University) ;
  • Kwon, Oh-Shin (School of Life Science, College of Natural Science, Kyungpook National University)
  • Received : 2017.04.12
  • Accepted : 2017.05.10
  • Published : 2017.06.30
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Abstract

Although doxorubicin (Dox)-induced oxidative stress is known to be associated with cytotoxicity, the precise mechanism remains unclear. Genotoxic stress not only generates free radicals, but also affects actin cytoskeleton stability. We showed that Dox-induced RhoA signaling stimulated actin cytoskeleton alterations, resulting in central stress fiber disruption at early time points and cell periphery cortical actin formation at a later stage, in HeLa cells. Interestingly, activation of a cofilin phosphatase, chronophin (CIN), was initially evoked by Dox-induced RhoA signaling, resulting in a rapid phosphorylated cofilin turnover leading to actin cytoskeleton remodeling. In addition, a novel interaction between CIN and $14-3-3{\zeta}$ was detected in the absence of Dox treatment. We demonstrated that CIN activity is quite contrary to $14-3-3{\zeta}$ binding, and the interaction leads to enhanced phosphorylated cofilin levels. Therefore, initial CIN activation regulation could be critical in Dox-induced actin cytoskeleton remodeling through RhoA/cofilin signaling.

Keywords

References

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