A positive feedback loop involving Haspin and Aurora B promotes CPC accumulation at centromeres in mitosis.
A positive feedback loop involving Haspin and Aurora B promotes CPC accumulation at centromeres in mitosis.
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DOI：
10.1016/j.cub.2011.05.016
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发表时间：
2011-06-21
期刊：
影响因子：
9.2
通讯作者：
Higgins, Jonathan M. G.
中科院分区：
文献类型：
--
作者：
Wang, Fangwei;Ulyanova, Natalia P.;van der Waal, Maike S.;Patnaik, Debasis;Lens, Susanne M. A.;Higgins, Jonathan M. G.
Haspin在有丝分裂期间磷酸化组蛋白H3的Thr-3（H3 T3 ph），为着丝粒处的染色体过客复合物（CPC）提供染色质结合位点，以调节染色体分离。H3 T3 ph在前中期越来越集中在内部着丝粒，但很少有人知道它的水平或位置以及随后的CPC染色体定位是如何调节的。此外，CPC与Shugoshin蛋白的结合有助于着丝粒极光B定位。将Shugoshins募集到着丝粒需要由动粒激酶Bub 1在T120（H2 AT 120 ph）处磷酸化组蛋白H2 A，但是该途径与H3 T3 ph协作的分子基础尚不清楚。在这里，我们表明，极光B磷酸化Haspin，以促进产生H3 T3 ph，极光B激酶活性是所需的正常染色体定位的CPC，表明极光B和Haspin之间的有丝分裂功能的密切联系。我们认为Aurora B活性触发CPC-Haspin-H3 T3 ph反馈环，促进染色质上H3 T3 ph的生成。我们还提供了Bub 1-Shugoshin-CPC途径提供的信号，促进了CPC-Haspin-H3 T3 ph反馈回路，特别是在着丝粒产生众所周知的CPC在这些区域的积累。
Haspin phosphorylates histone H3 at Thr-3 (H3T3ph) during mitosis, providing a chromatin binding site for the chromosomal passenger complex (CPC) at centromeres to regulate chromosome segregation. H3T3ph becomes increasingly focused at inner centromeres during prometaphase, but little is known about how its level or location and the consequent chromosomal localization of the CPC are regulated. In addition, CPC binding to Shugoshin proteins contributes to centromeric Aurora B localization. Recruitment of the Shugoshins to centromeres requires the phosphorylation of Histone H2A at T120 (H2AT120ph) by the kinetochore kinase Bub1, but the molecular basis for the collaboration of this pathway with H3T3ph has been unclear. Here, we show that Aurora B phosphorylates Haspin to promote generation of H3T3ph, and that Aurora B kinase activity is required for normal chromosomal localization of the CPC, indicating an intimate linkage between Aurora B and Haspin functions in mitosis. We propose that Aurora B activity triggers a CPC-Haspin-H3T3ph feedback loop that promotes generation of H3T3ph on chromatin. We also provide evidence that the Bub1-Shugoshin-CPC pathway supplies a signal that boosts the CPC-Haspin-H3T3ph feedback loop specifically at centromeres to produce the well-known accumulation of the CPC in these regions.
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影响因子：
3.3
作者：
Scrittori, L;Skoufias, DA;Margolis, RL
通讯作者：
Margolis, RL
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
影响因子：
4
作者：
Grewal, Shiv I. S.
通讯作者：
Grewal, Shiv I. S.
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：
56.9
作者：
Rosasco-Nitcher, Sara E.;Lan, Weijie;Stukenberg, P. Todd
通讯作者：
Stukenberg, P. Todd