• Journal of Life Science
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• v.18 no.4
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• pp.585-589
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• 2008

Chronophin is a phosphatase responsible for the dephosphorylation of cofilin, which regulates the rearrangement of actin cytoskeleton. It is also known as a phosphatase for pyrodoxal 5'-phosphate (PLP), an active form of vitamin $B_6$, and maintains the level of PLP in the cytoplasm. Since this phosphatase belongs to a HAD subfamily containing a cap domain, it is expected to undergo a conformational change for the binding of a substrate. However, the crystal structure of chronophin has a disulfide bridge between the cap and core domains preventing a movement of the cap domain against the core domain. It is possible that the disulfide bond between C91 and C221 was formed by an oxidation during the crystallization. Here, we obtained chronophin crystals under a reduced condition and determined the crystal structure. This reduced chronophin does not contain a disulfide bridge and shows a closed conformation like the oxidized form. It implies that an active chronophin binds its substrate under the closed conformation without the disulfide bond and shows a high substrate specificity in the cell.

• BMB Reports
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• v.50 no.6
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• pp.335-340
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• 2017

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.