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Aurora B kinase and protein phosphatase 1 have opposing roles in modulating kinetochore assembly

The outer kinetochore binds microtubules to control chromosome movement. Outer kinetochore assembly is restricted to mitosis, whereas the inner kinetochore remains tethered to centromeres throughout the cell cycle. The cues that regulate this transient assembly are unknown. We find that inhibition o...

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Autores principales: Emanuele, Michael J., Lan, Weijie, Jwa, Miri, Miller, Stephanie A., Chan, Clarence S.M., Stukenberg, P. Todd
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2315672/
https://www.ncbi.nlm.nih.gov/pubmed/18426974
http://dx.doi.org/10.1083/jcb.200710019
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author Emanuele, Michael J.
Lan, Weijie
Jwa, Miri
Miller, Stephanie A.
Chan, Clarence S.M.
Stukenberg, P. Todd
author_facet Emanuele, Michael J.
Lan, Weijie
Jwa, Miri
Miller, Stephanie A.
Chan, Clarence S.M.
Stukenberg, P. Todd
author_sort Emanuele, Michael J.
collection PubMed
description The outer kinetochore binds microtubules to control chromosome movement. Outer kinetochore assembly is restricted to mitosis, whereas the inner kinetochore remains tethered to centromeres throughout the cell cycle. The cues that regulate this transient assembly are unknown. We find that inhibition of Aurora B kinase significantly reduces outer kinetochore assembly in Xenopus laevis and human tissue culture cells, frog egg extracts, and budding yeast. In X. leavis M phase extracts, preassembled kinetochores disassemble after inhibiting Aurora B activity with either drugs or antibodies. Kinetochore disassembly, induced by Aurora B inhibition, is rescued by restraining protein phosphatase 1 (PP1) activity. PP1 is necessary for kinetochores to disassemble at the exit from M phase, and purified enzyme is sufficient to cause disassembly on isolated mitotic nuclei. These data demonstrate that Aurora B activity is required for kinetochore maintenance and that PP1 is necessary and sufficient to disassemble kinetochores. We suggest that Aurora B and PP1 coordinate cell cycle–dependent changes in kinetochore assembly though phosphorylation of kinetochore substrates.
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spelling pubmed-23156722008-10-21 Aurora B kinase and protein phosphatase 1 have opposing roles in modulating kinetochore assembly Emanuele, Michael J. Lan, Weijie Jwa, Miri Miller, Stephanie A. Chan, Clarence S.M. Stukenberg, P. Todd J Cell Biol Research Articles The outer kinetochore binds microtubules to control chromosome movement. Outer kinetochore assembly is restricted to mitosis, whereas the inner kinetochore remains tethered to centromeres throughout the cell cycle. The cues that regulate this transient assembly are unknown. We find that inhibition of Aurora B kinase significantly reduces outer kinetochore assembly in Xenopus laevis and human tissue culture cells, frog egg extracts, and budding yeast. In X. leavis M phase extracts, preassembled kinetochores disassemble after inhibiting Aurora B activity with either drugs or antibodies. Kinetochore disassembly, induced by Aurora B inhibition, is rescued by restraining protein phosphatase 1 (PP1) activity. PP1 is necessary for kinetochores to disassemble at the exit from M phase, and purified enzyme is sufficient to cause disassembly on isolated mitotic nuclei. These data demonstrate that Aurora B activity is required for kinetochore maintenance and that PP1 is necessary and sufficient to disassemble kinetochores. We suggest that Aurora B and PP1 coordinate cell cycle–dependent changes in kinetochore assembly though phosphorylation of kinetochore substrates. The Rockefeller University Press 2008-04-21 /pmc/articles/PMC2315672/ /pubmed/18426974 http://dx.doi.org/10.1083/jcb.200710019 Text en Copyright © 2008, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Research Articles
Emanuele, Michael J.
Lan, Weijie
Jwa, Miri
Miller, Stephanie A.
Chan, Clarence S.M.
Stukenberg, P. Todd
Aurora B kinase and protein phosphatase 1 have opposing roles in modulating kinetochore assembly
title Aurora B kinase and protein phosphatase 1 have opposing roles in modulating kinetochore assembly
title_full Aurora B kinase and protein phosphatase 1 have opposing roles in modulating kinetochore assembly
title_fullStr Aurora B kinase and protein phosphatase 1 have opposing roles in modulating kinetochore assembly
title_full_unstemmed Aurora B kinase and protein phosphatase 1 have opposing roles in modulating kinetochore assembly
title_short Aurora B kinase and protein phosphatase 1 have opposing roles in modulating kinetochore assembly
title_sort aurora b kinase and protein phosphatase 1 have opposing roles in modulating kinetochore assembly
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2315672/
https://www.ncbi.nlm.nih.gov/pubmed/18426974
http://dx.doi.org/10.1083/jcb.200710019
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