Histone H3 Thr-3 phosphorylation by Haspin positions Aurora B at centromeres in mitosis.

Histone H3 Thr-3 phosphorylation by Haspin positions Aurora B at centromeres in mitosis.
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DOI:
10.1126/science.1189435
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发表时间:
2010-10-08
期刊:
Science (New York, N.Y.)
影响因子:
--
通讯作者:
Higgins JM
Higgins JM
中科院分区:
其他
文献类型:
--
作者:
Wang F;Dai J;Daum JR;Niedzialkowska E;Banerjee B;Stukenberg PT;Gorbsky GJ;Higgins JM

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Aurora-B是染色体乘客复合物(CPC)的一个组成部分,在染色体分离和胞质分裂过程中正确的纺锤体-动粒附着所需。然而,将CPC募集到着丝粒的染色质因子尚不清楚。在这里,我们表明,磷酸化组蛋白-H3 Thr-3(H3 T3 ph)的Haspin是必要的CPC在着丝粒的积累,和CPC亚基生存素直接结合到H3 T3 ph。非结合性Survivin-D 70 A/D 71 A突变体不支持着丝粒CPC浓度,并且Haspin缺失和Survivin-D 70 A/D 71 A突变都减少了MCAK的着丝粒定位和紫杉醇中的有丝分裂检查点信号传导。Survivin-D 70 A/D 71 A突变和H3 T3 ph特异性抗体的显微注射都损害了着丝粒Aurora-B功能,但不能阻止胞质分裂。因此,Haspin产生的H3 T3 ph将CPC定位在着丝粒上,以在有丝分裂期间调节Aurora-B的选定靶标。
Aurora-B is a component of the Chromosomal Passenger Complex (CPC) required for correct spindle-kinetochore attachments during chromosome segregation and for cytokinesis. The chromatin factors that recruit the CPC to centromeres are unknown, however. Here we show that phosphorylation of Histone-H3 Thr-3 (H3T3ph) by Haspin is necessary for CPC accumulation at centromeres, and that the CPC subunit Survivin binds directly to H3T3ph. A non-binding Survivin-D70A/D71A mutant does not support centromeric CPC concentration and both Haspin depletion and Survivin-D70A/D71A mutation diminish centromere localization of MCAK and mitotic checkpoint signaling in taxol. Survivin-D70A/D71A mutation and microinjection of H3T3ph-specific antibody both compromise centromeric Aurora-B functions but do not prevent cytokinesis. Therefore, H3T3ph generated by Haspin positions the CPC at centromeres to regulate selected targets of Aurora-B during mitosis.
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