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

Author

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  • Midori Shimada

    (Graduate School of Medical Sciences, Nagoya City University)

  • Takahiro Goshima

    (Graduate School of Medical Sciences, Nagoya City University)

  • Hiromi Matsuo

    (Graduate School of Medical Sciences, Nagoya City University)

  • Yoshikazu Johmura

    (Graduate School of Medical Sciences, Nagoya City University)

  • Mayumi Haruta

    (Graduate School of Medical Sciences, Nagoya City University)

  • Kazuhiro Murata

    (Graduate School of Medical Sciences, Nagoya City University)

  • Hiromitsu Tanaka

    (Faculty of Pharmaceutical Sciences, Nagasaki International University, Sasebo)

  • Masahito Ikawa

    (Research Institute for Microbial Diseases, Osaka University, Suita)

  • Keiko Nakanishi

    (Institute for Developmental Research, Aichi Human Service Center)

  • Makoto Nakanishi

    (Graduate School of Medical Sciences, Nagoya City University
    Institute of Medical Science, The University of Tokyo)

Abstract

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.

Suggested Citation

  • Midori Shimada & Takahiro Goshima & Hiromi Matsuo & Yoshikazu Johmura & Mayumi Haruta & Kazuhiro Murata & Hiromitsu Tanaka & Masahito Ikawa & Keiko Nakanishi & Makoto Nakanishi, 2016. "Essential role of autoactivation circuitry on Aurora B-mediated H2AX-pS121 in mitosis," Nature Communications, Nature, vol. 7(1), pages 1-11, November.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms12059
    DOI: 10.1038/ncomms12059
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