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

First Author  Shimada M Year  2016
Journal  Nat Commun Volume  7
Pages  12059 PubMed ID  27389782
Mgi Jnum  J:240842 Mgi Id  MGI:5896497
Doi  10.1038/ncomms12059 Citation  Shimada M, et al. (2016) Essential role of autoactivation circuitry on Aurora B-mediated H2AX-pS121 in mitosis. Nat Commun 7:12059
abstractText  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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