Haspin inhibitors reveal centromeric functions of Aurora B in chromosome segregation.
Haspin inhibitors reveal centromeric functions of Aurora B in chromosome segregation.
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DOI：
10.1083/jcb.201205106
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发表时间：
2012-10-15
期刊：
影响因子：
--
通讯作者：
Higgins JM
中科院分区：
文献类型：
--
作者：
Wang F;Ulyanova NP;Daum JR;Patnaik D;Kateneva AV;Gorbsky GJ;Higgins JM
Haspin抑制剂揭示了着丝粒处的Aurora B是中期染色体排列和纺锤体检查点信号传导所必需的。Haspin使组蛋白H3在苏氨酸-3（H3 T3 ph）处磷酸化，从而在着丝粒处为极光B复合物提供对接位点。Aurora B的功能是纠正不正确的着丝粒-微管附着，并提醒纺锤体检查点存在未对齐的染色体。我们发现，Haspin抑制剂降低H3 T3 ph，导致着丝粒极光B的损失和减少的磷酸化着丝粒和动粒极光B基板。因此，中期染色体排列和纺锤体检查点信号传导受到损害。通过显微注射抗-H3 T3 ph抗体来表型复制这些效应。将Aurora B重定向到着丝粒部分恢复了着丝粒和动粒处的检查点信号传导和Aurora B依赖性磷酸化，绕过了对Haspin活性的需要。Haspin抑制剂对染色体臂上Aurora B磷酸化组蛋白H3丝氨酸10位（H3 S10 ph）没有明显影响，但在Aurora B再活化试验中，H3 S10 ph的恢复被延迟。Haspin抑制剂并不阻断Aurora B在后期纺锤体中间区的定位或胞质分裂中Aurora B的功能。因此，Haspin抑制剂揭示了Aurora B在染色体运动和纺锤体检查点信号传导中的着丝粒作用。
Haspin inhibitors reveal that Aurora B at centromeres is required for metaphase chromosome alignment and spindle checkpoint signaling. Haspin phosphorylates histone H3 at threonine-3 (H3T3ph), providing a docking site for the Aurora B complex at centromeres. Aurora B functions to correct improper kinetochore–microtubule attachments and alert the spindle checkpoint to the presence of misaligned chromosomes. We show that Haspin inhibitors decreased H3T3ph, resulting in loss of centromeric Aurora B and reduced phosphorylation of centromere and kinetochore Aurora B substrates. Consequently, metaphase chromosome alignment and spindle checkpoint signaling were compromised. These effects were phenocopied by microinjection of anti-H3T3ph antibodies. Retargeting Aurora B to centromeres partially restored checkpoint signaling and Aurora B–dependent phosphorylation at centromeres and kinetochores, bypassing the need for Haspin activity. Haspin inhibitors did not obviously affect phosphorylation of histone H3 at serine-10 (H3S10ph) by Aurora B on chromosome arms but, in Aurora B reactivation assays, recovery of H3S10ph was delayed. Haspin inhibitors did not block Aurora B localization to the spindle midzone in anaphase or Aurora B function in cytokinesis. Thus, Haspin inhibitors reveal centromeric roles of Aurora B in chromosome movement and spindle checkpoint signaling.
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DOI：
10.1073/pnas.0708800104
发表时间：
2007-12-18
影响因子：
11.1
作者：
Fedorov, Oleg;Marsden, Brian;Knapp, Stefan
通讯作者：
Knapp, Stefan
小分子黄质蛋白揭示了Aurora B在校正动型微管附着和维持纺锤体组装检查点方面的作用。
DOI：
10.1083/jcb.200208092
发表时间：
2003-04-28
期刊：
The Journal of cell biology
影响因子：
--
作者：
Hauf S;Cole RW;LaTerra S;Zimmer C;Schnapp G;Walter R;Heckel A;van Meel J;Rieder CL;Peters JM
通讯作者：
Peters JM
DOI：
10.1083/jcb.200710019
发表时间：
2008-04-21
期刊：
The Journal of cell biology
影响因子：
--
作者：
Emanuele MJ;Lan W;Jwa M;Miller SA;Chan CS;Stukenberg PT
通讯作者：
Stukenberg PT
影响因子：
8
作者：
Huertas, D.;Soler, M.;Moreto, J.;Villanueva, A.;Martinez, A.;Vidal, A.;Charlton, M.;Moffat, D.;Patel, S.;McDermott, J.;Owen, J.;Brotherton, D.;Krige, D.;Cuthill, S.;Esteller, M.
通讯作者：
Esteller, M.
影响因子：
--
作者：
Brito, Daniela A.;Rieder, Conly L.
通讯作者：
Rieder, Conly L.