Chronophin activation is necessary in Doxorubicin-induced actin cytoskeleton alteration

Su Jin Lee, Jeen Woo Park, Beom Sik Kang, Dong Seok Lee, Hyun Shik Lee, Sooyoung Choi, Oh Shin Kwon

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

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 14-3-3ζ was detected in the absence of Dox treatment. We demonstrated that CIN activity is quite contrary to 14-3-3ζ 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. [BMB Reports 2017; 50(6): 335-340].

Original languageEnglish
Pages (from-to)335-340
Number of pages6
JournalBMB Reports
Volume50
Issue number6
DOIs
StatePublished - 2017

Keywords

  • 14-3-3ζ
  • Actin cytoskeleton
  • Chronophin
  • Cofilin
  • Doxorubicin
  • RhoA signaling

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