Essential role of autoactivation circuitry on Aurora B-mediated H2AX-pS121 in mitosis

Proper deposition and activation of Aurora B at the centromere is critical for faithful chromosome segregation in mammals. However, the mechanistic basis for abrupt Aurora B kinase activation at the centromere has not yet been fully understood. We demonstrate here that Aurora B-mediated phosphorylat...

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Autores principales: Shimada, Midori, Goshima, Takahiro, Matsuo, Hiromi, Johmura, Yoshikazu, Haruta, Mayumi, Murata, Kazuhiro, Tanaka, Hiromitsu, Ikawa, Masahito, Nakanishi, Keiko, Nakanishi, Makoto
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
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Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4941122/
https://www.ncbi.nlm.nih.gov/pubmed/27389782
http://dx.doi.org/10.1038/ncomms12059
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author Shimada, Midori
Goshima, Takahiro
Matsuo, Hiromi
Johmura, Yoshikazu
Haruta, Mayumi
Murata, Kazuhiro
Tanaka, Hiromitsu
Ikawa, Masahito
Nakanishi, Keiko
Nakanishi, Makoto
author_facet Shimada, Midori
Goshima, Takahiro
Matsuo, Hiromi
Johmura, Yoshikazu
Haruta, Mayumi
Murata, Kazuhiro
Tanaka, Hiromitsu
Ikawa, Masahito
Nakanishi, Keiko
Nakanishi, Makoto
author_sort Shimada, Midori
collection PubMed
description Proper deposition and activation of Aurora B at the centromere is critical for faithful chromosome segregation in mammals. However, the mechanistic basis for abrupt Aurora B kinase activation at the centromere has not yet been fully understood. We demonstrate here that Aurora B-mediated phosphorylation of histone H2AX at serine 121 (H2AX-pS121) promotes Aurora B autophosphorylation and is essential for proper chromosome segregation. Aurora B-mediated H2AX-pS121 is specifically detected at the centromere during mitosis. H2AX depletion results in a severe defect in activation and deposition of Aurora B at this locus. A phosphomimic mutant of H2AX at S121 interacts with activated Aurora B more efficiently than wild-type in vitro. Taken together, these results propose a model in which Aurora B-mediated H2AX-pS121 probably provide a platform for Aurora B autoactivation circuitry at centromeres and thus play a pivotal role in proper chromosome segregation.
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spelling pubmed-49411222016-09-06 Essential role of autoactivation circuitry on Aurora B-mediated H2AX-pS121 in mitosis Shimada, Midori Goshima, Takahiro Matsuo, Hiromi Johmura, Yoshikazu Haruta, Mayumi Murata, Kazuhiro Tanaka, Hiromitsu Ikawa, Masahito Nakanishi, Keiko Nakanishi, Makoto Nat Commun Article Proper deposition and activation of Aurora B at the centromere is critical for faithful chromosome segregation in mammals. However, the mechanistic basis for abrupt Aurora B kinase activation at the centromere has not yet been fully understood. We demonstrate here that Aurora B-mediated phosphorylation of histone H2AX at serine 121 (H2AX-pS121) promotes Aurora B autophosphorylation and is essential for proper chromosome segregation. Aurora B-mediated H2AX-pS121 is specifically detected at the centromere during mitosis. H2AX depletion results in a severe defect in activation and deposition of Aurora B at this locus. A phosphomimic mutant of H2AX at S121 interacts with activated Aurora B more efficiently than wild-type in vitro. Taken together, these results propose a model in which Aurora B-mediated H2AX-pS121 probably provide a platform for Aurora B autoactivation circuitry at centromeres and thus play a pivotal role in proper chromosome segregation. Nature Publishing Group 2016-07-08 /pmc/articles/PMC4941122/ /pubmed/27389782 http://dx.doi.org/10.1038/ncomms12059 Text en Copyright © 2016, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Shimada, Midori
Goshima, Takahiro
Matsuo, Hiromi
Johmura, Yoshikazu
Haruta, Mayumi
Murata, Kazuhiro
Tanaka, Hiromitsu
Ikawa, Masahito
Nakanishi, Keiko
Nakanishi, Makoto
Essential role of autoactivation circuitry on Aurora B-mediated H2AX-pS121 in mitosis
title Essential role of autoactivation circuitry on Aurora B-mediated H2AX-pS121 in mitosis
title_full Essential role of autoactivation circuitry on Aurora B-mediated H2AX-pS121 in mitosis
title_fullStr Essential role of autoactivation circuitry on Aurora B-mediated H2AX-pS121 in mitosis
title_full_unstemmed Essential role of autoactivation circuitry on Aurora B-mediated H2AX-pS121 in mitosis
title_short Essential role of autoactivation circuitry on Aurora B-mediated H2AX-pS121 in mitosis
title_sort essential role of autoactivation circuitry on aurora b-mediated h2ax-ps121 in mitosis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4941122/
https://www.ncbi.nlm.nih.gov/pubmed/27389782
http://dx.doi.org/10.1038/ncomms12059
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