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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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Autor principal: Saurin, Adrian T.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2018
Materias:
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.
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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
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