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

Midori Shimada, Takahiro Goshima, Hiromi Matsuo, Yoshikazu Johmura, Mayumi Haruta, Kazuhiro Murata, Hiromitsu Tanaka, Masahito Ikawa, Keiko Nakanishi, Makoto Nakanishi

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13 Citations (Scopus)

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.

Original languageEnglish
Article number12059
JournalNature communications
Volume7
DOIs
Publication statusPublished - 08-07-2016

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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    Shimada, M., Goshima, T., Matsuo, H., Johmura, Y., Haruta, M., Murata, K., Tanaka, H., Ikawa, M., Nakanishi, K., & Nakanishi, M. (2016). Essential role of autoactivation circuitry on Aurora B-mediated H2AX-pS121 in mitosis. Nature communications, 7, [12059]. https://doi.org/10.1038/ncomms12059