Division of Biomedical Cell Biology, Warwick Medical School, University of Warwick, Gibbet Hill, Coventry, UK.
Dev Cell. 2011 Jun 14;20(6):739-50. doi: 10.1016/j.devcel.2011.05.008.
The spindle checkpoint is the prime cell-cycle control mechanism that ensures sister chromatids are bioriented before anaphase takes place. Aurora B kinase, the catalytic subunit of the chromosome passenger complex, both destabilizes kinetochore attachments that do not generate tension and simultaneously maintains the spindle checkpoint signal. However, it is unclear how the checkpoint is silenced following chromosome biorientation. We demonstrate that association of type 1 phosphatase (PP1(Dis2)) with both the N terminus of Spc7 and the nonmotor domains of the Klp5-Klp6 (kinesin-8) complex is necessary to counteract Aurora B kinase to efficiently silence the spindle checkpoint. The role of Klp5 and Klp6 in checkpoint silencing is specific to this class of kinesin and independent of their motor activities. These data demonstrate that at least two distinct pools of PP1, one kinetochore associated and the other motor associated, are needed to silence the spindle checkpoint.
纺锤体检查点是一种主要的细胞周期调控机制，可确保姐妹染色单体在后期发生之前进行双定向。作为染色体乘客复合物的催化亚基，极光激酶（Aurora B kinase）可同时破坏未产生张力的动粒附着，并维持纺锤体检查点信号。然而，染色体双定向后检查点如何沉默尚不清楚。我们证明，类型 1 磷酸酶（PP1（Dis2））与 Spc7 的 N 端以及 Klp5-Klp6（驱动蛋白-8）复合物的非马达结构域的结合对于拮抗极光激酶以有效沉默纺锤体检查点是必需的。Klp5 和 Klp6 在检查点沉默中的作用是这种驱动蛋白特有的，并且不依赖于它们的运动活性。这些数据表明，至少有两种不同的 PP1 池，一种与动粒相关，另一种与马达相关，需要用于沉默纺锤体检查点。
