Bub1 is required for kinetochore localization of BubR1, Cenp-E, Cenp-F and Mad2, and chromosome congression
Bub1 is required for kinetochore localization of BubR1, Cenp-E, Cenp-F and Mad2, and chromosome congression
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DOI：
10.1242/jcs.01006
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发表时间：
2004-03-15
影响因子：
4
通讯作者：
Taylor, SS
中科院分区：
文献类型：
--
作者：
Johnson, VL;Scott, MIF;Taylor, SS
在有丝分裂过程中，纺锤体检查点相关蛋白以确定的顺序向着丝点聚集。蛋白激酶Bub1在有丝分裂早期定位于着丝点，其次是Cenp-F、BubR1、Cenp-E，最后是Mad2。利用RNA干扰，我们研究了这种结合顺序是否反映了人类体细胞的依赖程度。具体来说，我们表明Bub1在着丝点检查点蛋白的组装中起关键作用，这是随后定位Cenp-F、BubR1、Cenp-E和Mad2所必需的。与非洲爪蟾的研究相反，我们还表明Bub1不是着丝点定位所必需的。对Bub1的抑制增加了中期染色体滞后的细胞数量，表明Bub1在染色体聚集中起作用。然而，无论是在正常有丝分裂期间，还是在对纺锤体损伤的反应中，抑制Bub1似乎都不会损害纺锤体检查点的功能。这提出了在没有Bub1的情况下，其他机制参与纺锤体检查点功能的可能性。
During mitosis, the recruitment of spindle-checkpoint-associated proteins to the kinetochore occurs in a defined order. The protein kinase Bub1 localizes to the kinetochore very early during mitosis, followed by Cenp-F, BubR1, Cenp-E and finally Mad2. Using RNA interference, we have investigated whether this order of binding reflects a level of dependency in human somatic cells. Specifically, we show that Bub1 plays a key role in the assembly of checkpoint proteins at the kinetochore, being required for the subsequent localization of Cenp-F, BubR1, Cenp-E and Mad2. In contrast to studies in Xenopus, we also show that Bub1 is not required for kinetochore localization of Bub1. Repression of Bub1 increases the number of cells with lagging chromosomes at metaphase, suggesting that Bub1 plays a role in chromosome congression. However, repression of Bub1 does not appear to compromise spindle checkpoint function either during normal mitosis or in response to spindle damage. This raises the possibility that, in the absence of Bub1, other mechanisms contribute to spindle checkpoint function.