Cdk1 promotes kinetochore bi-orientation and regulates Cdc20 expression during recovery from spindle checkpoint arrest
Cdk1 promotes kinetochore bi-orientation and regulates Cdc20 expression during recovery from spindle checkpoint arrest
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DOI：
10.1038/emboj.2011.385
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发表时间：
2012-01-18
期刊：
影响因子：
11.4
通讯作者：
Surana, Uttam
中科院分区：
文献类型：
--
作者：
Liang, Hongqing;Lim, Hong Hwa;Surana, Uttam
纺锤体组装检查点（SAC），一个进化上保守的监视途径，防止染色体分离的条件下，破坏着丝粒微管附着。检查点激活刺激的去除启动恢复，在此期间纺锤体完整性恢复，动粒变得双向，细胞启动后期。恢复是否在检查点刺激去除后被动地增强，或者需要特定效应物的介导仍然不确定。在这里，我们报告了两个未被识别的功能酵母Cdk 1需要从SAC诱导的逮捕有效恢复。我们发现，Cdk 1促进动粒双取向在恢复过程中，通过抑制过早的纺锤体伸长，从而熄灭SAC信号。此外，Cdk 1是维持Cdc 20的表达所必需的，Cdc 20是后期进展所需的后期促进复合物/环体（APC/C）的激活剂。我们提出了一个模型，其中Cdk 1活性促进恢复SAC诱导的有丝分裂阻滞通过调节双向和APC/C活性。我们的研究结果提供了新的见解有丝分裂的调节，并具有抗有丝分裂药物的治疗效果的影响。The EMBO Journal（2012）31，403-416. doi：10.1038/daj.2011.385; 2011年11月4日在线发布
The spindle assembly checkpoint (SAC), an evolutionarily conserved surveillance pathway, prevents chromosome segregation in response to conditions that disrupt the kinetochore-microtubule attachment. Removal of the checkpoint-activating stimulus initiates recovery during which spindle integrity is restored, kinetochores become bi-oriented, and cells initiate anaphase. Whether recovery ensues passively after the removal of checkpoint stimulus, or requires mediation by specific effectors remains uncertain. Here, we report two unrecognized functions of yeast Cdk1 required for efficient recovery from SAC-induced arrest. We show that Cdk1 promotes kinetochore bi-orientation during recovery by restraining premature spindle elongation thereby extinguishing SAC signalling. Moreover, Cdk1 is essential for sustaining the expression of Cdc20, an activator of the anaphase promoting complex/cyclosome (APC/C) required for anaphase progression. We suggest a model in which Cdk1 activity promotes recovery from SAC-induced mitotic arrest by regulating bi-orientation and APC/C activity. Our findings provide fresh insights into the regulation of mitosis and have implications for the therapeutic efficacy of anti-mitotic drugs. The EMBO Journal (2012) 31, 403-416. doi:10.1038/emboj.2011.385; Published online 4 November 2011