The activity regulation of the mitotic centromere-associated kinesin by Polo-like kinase 1.

Andreas Ritter,Susanne Roth,Mourad Sanhaji,Juping Yuan,Kerstin Steinhäuser,Frank Louwen

doi:10.18632/oncotarget.2843

Andreas Ritter, Susanne Roth + Show 4 more

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https://doi.org/10.18632/oncotarget.2843

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Abstract

The mitotic centromere-associated kinesin (MCAK), a potent microtubule depolymerase, is involved in regulating microtubule dynamics. The activity and subcellular localization of MCAK are tightly regulated by key mitotic kinases, such as Polo-like kinase 1 (Plk1) by phosphorylating multiple residues in MCAK. Since Plk1 phosphorylates very often different residues of substrates at different stages, we have dissected individual phosphorylation of MCAK by Plk1 and characterized its function in more depth. We have recently shown that S621 in MCAK is the major phosphorylation site of Plk1, which is responsible for regulating MCAK's degradation by promoting the association of MCAK with APC/CCdc20. In the present study, we have addressed another two residues phosphorylated by Plk1, namely S632/S633 in the C-terminus of MCAK. Our data suggest that Plk1 phosphorylates S632/S633 and regulates its catalytic activity in mitosis. This phosphorylation is required for proper spindle assembly during early phases of mitosis. The subsequent dephosphorylation of S632/S633 might be necessary to timely align the chromosomes onto the metaphase plate. Therefore, our studies suggest new mechanisms by which Plk1 regulates MCAK: the degradation of MCAK is controlled by Plk1 phosphorylation on S621, whereas its activity is modulated by Plk1 phosphorylation on S632/S633 in mitosis.

Highlights

The kinesin-13 family members of microtubule (MT) depolymerizers play essential roles in controlling MT dynamics [1,2,3]
The activity as well as the subcellular localization of mitotic centromere-associated kinesin (MCAK) are precisely regulated by phosphorylation events that are executed by a number of important kinases, such as Aurora B, Aurora A, cyclindependent kinase 1 (Cdk1) and Polo-like kinase 1 (Plk1) in mitosis [7,8,9,10,11,12]
This finding shows that the S632/S633 residues are important phosphorylation sites for Plk1, beside the major phosphorylation site S621 in MCAK

Summary

Introduction

The kinesin-13 family members of microtubule (MT) depolymerizers play essential roles in controlling MT dynamics [1,2,3]. The members of the kinesin-13 family do not use the energy from ATP turnover to move directionally along MTs but, instead, depolymerize them by disassembling tubulin subunits from the polymer end [4,5]. This family is characterized by the localization of the conserved kinesin motor domain in the middle of the polypeptide [6]. Plk promotes the catalytic activity of MCAK by phosphorylating the five residues at its C-terminus, regulating MT-dynamics and improving the correction of kinetochore-MT error-attachments [12]. We have addressed another two residues phosphorylated by Plk, namely S632/S633 in the C-terminal domain of MCAK, and explored the function of the phosphorylation of these residues in mitosis

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