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Kinase and Phosphatase Cross-Talk at the Kinetochore
Multiple kinases and phosphatases act on the kinetochore to control chromosome segregation: Aurora B, Mps1, Bub1, Plk1, Cdk1, PP1, and PP2A-B56, have all been shown to regulate both kinetochore-microtubule attachments and the spindle assembly checkpoint. Given that so many kinases and phosphatases c...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2018
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6018199/ https://www.ncbi.nlm.nih.gov/pubmed/29971233 http://dx.doi.org/10.3389/fcell.2018.00062 |
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author | Saurin, Adrian T. |
author_facet | Saurin, Adrian T. |
author_sort | Saurin, Adrian T. |
collection | PubMed |
description | Multiple kinases and phosphatases act on the kinetochore to control chromosome segregation: Aurora B, Mps1, Bub1, Plk1, Cdk1, PP1, and PP2A-B56, have all been shown to regulate both kinetochore-microtubule attachments and the spindle assembly checkpoint. Given that so many kinases and phosphatases converge onto two key mitotic processes, it is perhaps not surprising to learn that they are, quite literally, entangled in cross-talk. Inhibition of any one of these enzymes produces secondary effects on all the others, which results in a complicated picture that is very difficult to interpret. This review aims to clarify this picture by first collating the direct effects of each enzyme into one overarching schematic of regulation at the Knl1/Mis12/Ndc80 (KMN) network (a major signaling hub at the outer kinetochore). This schematic will then be used to discuss the implications of the cross-talk that connects these enzymes; both in terms of why it may be needed to produce the right type of kinetochore signals and why it nevertheless complicates our interpretations about which enzymes control what processes. Finally, some general experimental approaches will be discussed that could help to characterize kinetochore signaling by dissociating the direct from indirect effect of kinase or phosphatase inhibition in vivo. Together, this review should provide a framework to help understand how a network of kinases and phosphatases cooperate to regulate two key mitotic processes. |
format | Online Article Text |
id | pubmed-6018199 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-60181992018-07-03 Kinase and Phosphatase Cross-Talk at the Kinetochore Saurin, Adrian T. Front Cell Dev Biol Cell and Developmental Biology Multiple kinases and phosphatases act on the kinetochore to control chromosome segregation: Aurora B, Mps1, Bub1, Plk1, Cdk1, PP1, and PP2A-B56, have all been shown to regulate both kinetochore-microtubule attachments and the spindle assembly checkpoint. Given that so many kinases and phosphatases converge onto two key mitotic processes, it is perhaps not surprising to learn that they are, quite literally, entangled in cross-talk. Inhibition of any one of these enzymes produces secondary effects on all the others, which results in a complicated picture that is very difficult to interpret. This review aims to clarify this picture by first collating the direct effects of each enzyme into one overarching schematic of regulation at the Knl1/Mis12/Ndc80 (KMN) network (a major signaling hub at the outer kinetochore). This schematic will then be used to discuss the implications of the cross-talk that connects these enzymes; both in terms of why it may be needed to produce the right type of kinetochore signals and why it nevertheless complicates our interpretations about which enzymes control what processes. Finally, some general experimental approaches will be discussed that could help to characterize kinetochore signaling by dissociating the direct from indirect effect of kinase or phosphatase inhibition in vivo. Together, this review should provide a framework to help understand how a network of kinases and phosphatases cooperate to regulate two key mitotic processes. Frontiers Media S.A. 2018-06-19 /pmc/articles/PMC6018199/ /pubmed/29971233 http://dx.doi.org/10.3389/fcell.2018.00062 Text en Copyright © 2018 Saurin. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Cell and Developmental Biology Saurin, Adrian T. Kinase and Phosphatase Cross-Talk at the Kinetochore |
title | Kinase and Phosphatase Cross-Talk at the Kinetochore |
title_full | Kinase and Phosphatase Cross-Talk at the Kinetochore |
title_fullStr | Kinase and Phosphatase Cross-Talk at the Kinetochore |
title_full_unstemmed | Kinase and Phosphatase Cross-Talk at the Kinetochore |
title_short | Kinase and Phosphatase Cross-Talk at the Kinetochore |
title_sort | kinase and phosphatase cross-talk at the kinetochore |
topic | Cell and Developmental Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6018199/ https://www.ncbi.nlm.nih.gov/pubmed/29971233 http://dx.doi.org/10.3389/fcell.2018.00062 |
work_keys_str_mv | AT saurinadriant kinaseandphosphatasecrosstalkatthekinetochore |