title: Essential role of autoactivation circuitry on Aurora B-mediated H2AX-pS121 in mitosis.
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.
authors.affiliation: Department of Cell Biology, Graduate School of Medical Sciences, Nagoya City University, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan.
authors.forename: Midori
authors.initials: M
authors.lastname: Shimada
authors.affiliation: Department of Cell Biology, Graduate School of Medical Sciences, Nagoya City University, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Goshima
authors.affiliation: Department of Cell Biology, Graduate School of Medical Sciences, Nagoya City University, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Matsuo
authors.affiliation: Department of Cell Biology, Graduate School of Medical Sciences, Nagoya City University, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan.
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Johmura
authors.affiliation: Department of Cell Biology, Graduate School of Medical Sciences, Nagoya City University, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan.
authors.forename: Mayumi
authors.initials: M
authors.lastname: Haruta
authors.affiliation: Department of Cell Biology, Graduate School of Medical Sciences, Nagoya City University, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Murata
authors.affiliation: Faculty of Pharmaceutical Sciences, Nagasaki International University, Sasebo, Nagasaki 859-3298, Japan.
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Tanaka
authors.affiliation: Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan.
authors.forename: Masahito
authors.identifier: 0000-0001-9859-6217
authors.initials: M
authors.lastname: Ikawa
authors.affiliation: Department of Perinatology, Institute for Developmental Research, Aichi Human Service Center, 713-8 Kamiya-cho, Kasugai, Aichi 489-0392, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Nakanishi
authors.affiliation: Department of Cell Biology, Graduate School of Medical Sciences, Nagoya City University, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan.|Division of Cancer Cell Biology, Department of Cancer Biology, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Nakanishi
mesh_terms: D000818:Animals; D064107:Aurora Kinase B / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D020090:Chromosome Segregation; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D006367:HeLa Cells; D006657:Histones / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D018386:Kinetochores / Q000378:metabolism / Q000648:ultrastructure; D051379:Mice; D018345:Mice, Knockout; D008938:Mitosis; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D012694:Serine / Q000378:metabolism*; D008941:Spindle Apparatus / Q000378:metabolism / Q000648:ultrastructure
chemical_list: C468783:H2AX protein, human; C530657:Haspin protein, mouse; D006657:Histones; D047908:Intracellular Signaling Peptides and Proteins; D034741:RNA, Small Interfering; D012694:Serine; C576921:AURKB protein, human; D064107:Aurora Kinase B; D017346:Protein Serine-Threonine Kinases