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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...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2014
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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. |
format | Online Article Text |
id | pubmed-4102797 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
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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