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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Detalles Bibliográficos
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
Materias:
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
Descripción
Sumario: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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