Microtubules do not promote mitotic slippage when the spindle assembly checkpoint cannot be satisfied.

Microtubules do not promote mitotic slippage when the spindle assembly checkpoint cannot be satisfied.
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DOI:
10.1083/jcb.200805072
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发表时间:
2008-08-25
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
Rieder CL
Rieder CL
中科院分区:
其他
文献类型:
--
作者:
Brito DA;Yang Z;Rieder CL

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当不能满足纺锤体组装检查点(SAC)时,细胞通过有丝分裂滑移退出有丝分裂。在微管(MT)毒物中,滑移需要细胞周期蛋白B蛋白水解,并且似乎在允许一些MT组装的药物浓度下加速。为了确定MT是否加速滑移,我们跟踪了暴露于各种纺锤体毒物的人RPE-1细胞中的有丝分裂。在37°C下,抑制MT组装的诺考达唑、秋水仙胺或长春碱浓度下的有丝分裂持续时间从20小时到30小时不等,揭示了不同的MT毒物在滑移期间不同地抑制细胞周期蛋白B破坏速率。Eg 5抑制剂诱导单极纺锤体而不破坏MT动力学,其有丝分裂的持续时间与缺乏MT的细胞相同。因此,在存在许多未连接的动粒的情况下,MT不会加速滑动。最后,与缺乏MT的细胞相比,在允许MT组装的纺锤体毒素浓度范围内,有丝分裂的退出加速,因为SAC在异常纺锤体上变得满意,而不是因为滑移加速。
When the spindle assembly checkpoint (SAC) cannot be satisfied, cells exit mitosis via mitotic slippage. In microtubule (MT) poisons, slippage requires cyclin B proteolysis, and it appears to be accelerated in drug concentrations that allow some MT assembly. To determine if MTs accelerate slippage, we followed mitosis in human RPE-1 cells exposed to various spindle poisons. At 37°C, the duration of mitosis in nocodazole, colcemid, or vinblastine concentrations that inhibit MT assembly varied from 20 to 30 h, revealing that different MT poisons differentially depress the cyclin B destruction rate during slippage. The duration of mitosis in Eg5 inhibitors, which induce monopolar spindles without disrupting MT dynamics, was the same as in cells lacking MTs. Thus, in the presence of numerous unattached kinetochores, MTs do not accelerate slippage. Finally, compared with cells lacking MTs, exit from mitosis is accelerated over a range of spindle poison concentrations that allow MT assembly because the SAC becomes satisfied on abnormal spindles and not because slippage is accelerated.
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