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bioRxiv · 10.1101/2021.04.20.440650

Compartimentalized control of Cdk1 drives mitotic spindle assembly

Serpico, A. F.·Febbraro, F.·Pisauro, C.·Grieco, D.
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Abstract

During cell division, dramatic microtubular rearrangements driven by cyclin B-cdk1 (Cdk1) kinase activity mark mitosis onset leading to interphase cytoskeleton dissolution and mitotic spindle assembly. Once activated by Cdc25, that reverses inhibitory phosphorylation operated by Wee1/Myt1, Cdk1 clears the cytoplasm from microtubules by inhibiting microtubule associated proteins (MAPs) with microtubule growth-promoting properties. Nevertheless, some of these MAPs are required for spindle assembly, creating quite a conundrum. We show here that a Cdk1 fraction bound to spindle structures escaped Cdc25 action and remained inhibited by phosphorylation (i-Cdk1) in mitotic human cells. Loss or restoration of i-Cdk1 inhibited or promoted spindle assembly, respectively. Furthermore, polymerizing spindle microtubules fostered i-Cdk1 by aggregating with Wee1 and excluding Cdc25. Our data reveal that spindle assembly relies on compartmentalized control of Cdk1 activity.

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Serpico, A. F., Febbraro, F., Pisauro, C., Grieco, D.. 2021-04-20. Compartimentalized control of Cdk1 drives mitotic spindle assembly. https://doi.org/10.1101/2021.04.20.440650

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