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Journal Articles Cell Cycle Year : 2015

Kizuna is a novel mitotic substrate for CDC25B phosphatase

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Abstract

CDC25 dual-specificity phosphatases play a central role in cell cycle control through the activation of Cyclin-Dependent Kinases (CDKs). Expression during mitosis of a stabilized CDC25B mutant (CDC25B-DDA), which cannot interact with the F-box protein βTrCP for proteasome-dependent degradation, causes mitotic defects and chromosome segregation errors in mammalian cells. We found, using the same CDC25B mutant, that stabilization and failure to degrade CDC25B during mitosis lead to the appearance of multipolar spindle cells resulting from a fragmentation of pericentriolar material (PCM) and abolish mitotic Plk1-dependent phosphorylation of Kizuna (Kiz), which is essential for the function of Kiz in maintaining spindle pole integrity. Thus, in mitosis Kiz is a new substrate of CDC25B whose dephosphorylation following CDC25B stabilization leads to the formation of multipolar spindles. Furthermore, endogenous Kiz and CDC25B interact only in mitosis, suggesting that Kiz phosphorylation depends on a balance between CDC25B and Plk1 activities. Our data identify a novel mitotic substrate of CDC25B phosphatase that plays a key role in mitosis control.

Dates and versions

hal-02353356 , version 1 (07-11-2019)

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Yann Thomas, Marion Peter, Francisca Méchali, Jean-Marie Blanchard, Olivier Coux, et al.. Kizuna is a novel mitotic substrate for CDC25B phosphatase. Cell Cycle, 2015, 13 (24), pp.3867-3877. ⟨10.4161/15384101.2014.972882⟩. ⟨hal-02353356⟩
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