Dual recognition of chromatin and microtubules by INCENP is important for mitotic progression.
Dual recognition of chromatin and microtubules by INCENP is important for mitotic progression.
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DOI：
10.1083/jcb.201609061
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发表时间：
2017-04-03
期刊：
影响因子：
--
通讯作者：
Funabiki H
中科院分区：
文献类型：
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作者：
Wheelock MS;Wynne DJ;Tseng BS;Funabiki H
染色体乘客复合物有助于有丝分裂检查点的激活，由INCENP、Survivin、Borealin和激酶Aurora B组成。Wheelock等人定义了INCENP结构域结合染色质和微管在有丝分裂检查点中的作用。由内着丝粒蛋白（INCENP）、Survivin、Borealin和激酶Aurora B组成的染色体乘客复合物（CPC）有助于有丝分裂检查点的激活。对保护竞争委员会职能的管理仍不明确。在这里，我们发现，除了生存素和Borealin，单α-螺旋（SAH）结构域的INCENP支持CPC定位到染色质和有丝分裂检查点。INCENP SAH结构域还介导INCENP的微管结合，其由SAH结构域侧翼片段的细胞周期蛋白依赖性激酶介导的磷酸化负调控。SAH结构域的微管结合能力对于微管动力学受抑制的条件下的有丝分裂停滞是重要的，并且有丝分裂停滞的持续时间决定了细胞死亡的概率，但不是时间。尽管INCENP独立靶向微管或动粒/着丝粒促进有丝分裂检查点，但它不足以实现稳健的有丝分裂阻滞。总之，我们的研究结果表明，CPC对染色质和微管的双重识别对于有丝分裂中检查点的维持和细胞命运的确定是重要的。
The chromosomal passenger complex contributes to the activation of the mitotic checkpoint and is composed of INCENP, Survivin, Borealin, and the kinase Aurora B. Wheelock et al. define the role of the INCENP domains binding chromatin and microtubules in the mitotic checkpoint. The chromosomal passenger complex (CPC), composed of inner centromere protein (INCENP), Survivin, Borealin, and the kinase Aurora B, contributes to the activation of the mitotic checkpoint. The regulation of CPC function remains unclear. Here, we reveal that in addition to Survivin and Borealin, the single α-helix (SAH) domain of INCENP supports CPC localization to chromatin and the mitotic checkpoint. The INCENP SAH domain also mediates INCENP’s microtubule binding, which is negatively regulated by Cyclin-dependent kinase–mediated phosphorylation of segments flanking the SAH domain. The microtubule-binding capacity of the SAH domain is important for mitotic arrest in conditions of suppressed microtubule dynamics, and the duration of mitotic arrest dictates the probability, but not the timing, of cell death. Although independent targeting of INCENP to microtubules or the kinetochore/centromere promotes the mitotic checkpoint, it is insufficient for a robust mitotic arrest. Altogether, our results demonstrate that dual recognition of chromatin and microtubules by CPC is important for checkpoint maintenance and determination of cell fate in mitosis.