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Polo-like kinase 1 regulates the stability of the mitotic centromere-associated kinesin in mitosis

Proper bi-orientation of chromosomes is critical for the accurate segregation of chromosomes in mitosis. A key regulator of this process is MCAK, the mitotic centromere-associated kinesin. During mitosis the activity and localization of MCAK are regulated by mitotic key kinases including Plk1 and Au...

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Autores principales: Sanhaji, Mourad, Ritter, Andreas, Belsham, Hannah R., Friel, Claire T., Roth, Susanne, Louwen, Frank, Yuan, Juping
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4102797/
https://www.ncbi.nlm.nih.gov/pubmed/24931513
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author Sanhaji, Mourad
Ritter, Andreas
Belsham, Hannah R.
Friel, Claire T.
Roth, Susanne
Louwen, Frank
Yuan, Juping
author_facet Sanhaji, Mourad
Ritter, Andreas
Belsham, Hannah R.
Friel, Claire T.
Roth, Susanne
Louwen, Frank
Yuan, Juping
author_sort Sanhaji, Mourad
collection PubMed
description Proper bi-orientation of chromosomes is critical for the accurate segregation of chromosomes in mitosis. A key regulator of this process is MCAK, the mitotic centromere-associated kinesin. During mitosis the activity and localization of MCAK are regulated by mitotic key kinases including Plk1 and Aurora B. We show here that S621 in the MCAK's C-terminal domain is the major phosphorylation site for Plk1. This phosphorylation regulates MCAK's stability and facilitates its recognition by the ubiquitin/proteasome dependent APC/C(Cdc20) pathway leading to its D-box dependent degradation in mitosis. While phosphorylation of S621 does not directly affect its microtubule depolymerising activity, loss of Plk1 phosphorylation on S621 indirectly enhances its depolymerization activity in vivo by stabilizing MCAK, leading to an increased level of protein. Interfering with phosphorylation at S621 causes spindle formation defects and chromosome misalignments. Therefore, this study suggests a new mechanism by which Plk1 regulates MCAK: by regulating its degradation and hence controlling its turnover in mitosis.
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spelling pubmed-41027972014-07-23 Polo-like kinase 1 regulates the stability of the mitotic centromere-associated kinesin in mitosis Sanhaji, Mourad Ritter, Andreas Belsham, Hannah R. Friel, Claire T. Roth, Susanne Louwen, Frank Yuan, Juping Oncotarget Research Paper Proper bi-orientation of chromosomes is critical for the accurate segregation of chromosomes in mitosis. A key regulator of this process is MCAK, the mitotic centromere-associated kinesin. During mitosis the activity and localization of MCAK are regulated by mitotic key kinases including Plk1 and Aurora B. We show here that S621 in the MCAK's C-terminal domain is the major phosphorylation site for Plk1. This phosphorylation regulates MCAK's stability and facilitates its recognition by the ubiquitin/proteasome dependent APC/C(Cdc20) pathway leading to its D-box dependent degradation in mitosis. While phosphorylation of S621 does not directly affect its microtubule depolymerising activity, loss of Plk1 phosphorylation on S621 indirectly enhances its depolymerization activity in vivo by stabilizing MCAK, leading to an increased level of protein. Interfering with phosphorylation at S621 causes spindle formation defects and chromosome misalignments. Therefore, this study suggests a new mechanism by which Plk1 regulates MCAK: by regulating its degradation and hence controlling its turnover in mitosis. Impact Journals LLC 2014-03-24 /pmc/articles/PMC4102797/ /pubmed/24931513 Text en Copyright: © 2014 Sanhaji et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Sanhaji, Mourad
Ritter, Andreas
Belsham, Hannah R.
Friel, Claire T.
Roth, Susanne
Louwen, Frank
Yuan, Juping
Polo-like kinase 1 regulates the stability of the mitotic centromere-associated kinesin in mitosis
title Polo-like kinase 1 regulates the stability of the mitotic centromere-associated kinesin in mitosis
title_full Polo-like kinase 1 regulates the stability of the mitotic centromere-associated kinesin in mitosis
title_fullStr Polo-like kinase 1 regulates the stability of the mitotic centromere-associated kinesin in mitosis
title_full_unstemmed Polo-like kinase 1 regulates the stability of the mitotic centromere-associated kinesin in mitosis
title_short Polo-like kinase 1 regulates the stability of the mitotic centromere-associated kinesin in mitosis
title_sort polo-like kinase 1 regulates the stability of the mitotic centromere-associated kinesin in mitosis
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4102797/
https://www.ncbi.nlm.nih.gov/pubmed/24931513
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