BubR1 recruitment to the kinetochore via Bub1 enhances spindle assembly checkpoint signaling.
BubR1 recruitment to the kinetochore via Bub1 enhances spindle assembly checkpoint signaling.
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DOI：
10.1091/mbc.e22-03-0085
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发表时间：
2022-09-01
影响因子：
3.3
通讯作者：
Joglekar, Ajit P.
中科院分区：
文献类型：
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作者：
Banerjee, Anand;Chen, Chu;Humphrey, Lauren;Tyson, John J.;Joglekar, Ajit P.
在有丝分裂过程中，分裂细胞中未连接的动粒激活纺锤体组装检查点（SAC），并通过产生后期抑制性有丝分裂检查点复合物（MCC）来延迟后期开始。这些动粒通过募集其组成蛋白（包括BubR1）来产生MCC。原则上，BubR1的招聘信号激动素应增加其局部浓度，促进MCC的形成。然而，在人类细胞中，BubR1主要被认为使SAC对沉默敏感。BubR1自身定位于信号转导着丝粒是否增强SAC信号转导仍然未知。因此，我们使用异位SAC激活（eSAC）系统分离两个分子，招募BubR1的动粒，检查点蛋白Bub1和KI和MELT基序的动粒蛋白KNL1，并观察他们的贡献eSAC信号。我们的定量分析和数学建模表明，Bub1介导的BubR1招聘到人类动粒促进SAC信号传导，并突出BubR1的双重作用，直接加强SAC和沉默它间接。
During mitosis, unattached kinetochores in a dividing cell activate the spindle assembly checkpoint (SAC) and delay anaphase onset by generating the anaphase-inhibitory mitotic checkpoint complex (MCC). These kinetochores generate the MCC by recruiting its constituent proteins, including BubR1. In principle, BubR1 recruitment to signaling kinetochores should increase its local concentration and promote MCC formation. However, in human cells BubR1 is mainly thought to sensitize the SAC to silencing. Whether BubR1 localization to signaling kinetochores by itself enhances SAC signaling remains unknown. Therefore, we used ectopic SAC activation (eSAC) systems to isolate two molecules that recruit BubR1 to the kinetochore, the checkpoint protein Bub1 and the KI and MELT motifs in the kinetochore protein KNL1, and observed their contribution to eSAC signaling. Our quantitative analyses and mathematical modeling show that Bub1-mediated BubR1 recruitment to the human kinetochore promotes SAC signaling and highlight BubR1’s dual role of strengthening the SAC directly and silencing it indirectly.