Drosophila Polo regulates the spindle assembly checkpoint through Mps1-dependent BubR1 phosphorylation
Drosophila Polo regulates the spindle assembly checkpoint through Mps1-dependent BubR1 phosphorylation
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DOI：
10.1038/emboj.2013.109
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发表时间：
2013-06-12
期刊：
影响因子：
11.4
通讯作者：
Sunkel, Claudio E.
中科院分区：
文献类型：
--
作者：
Conde, Carlos;Osswald, Mariana;Sunkel, Claudio E.
真核细胞分裂期间基因组稳定性的维持依赖于纺锤体组装检查点（SAC），其防止有丝分裂退出，直到所有染色体正确地附着到纺锤体。波罗是一种有丝分裂激酶，被认为参与SAC的功能，但其作用仍然是难以捉摸的。我们证明，波罗和极光B功能的相互依赖性包括一个积极的反馈回路，促进Mps 1动粒定位和活动。组成型活性波罗的表达恢复正常的Mps 1动粒水平，甚至在极光B抑制后，突出了波罗在Mps 1募集到极光B下游的未连接动粒中的作用。我们还表明，Mps 1动粒定位所需的BubR 1过度磷酸化和形成的3F 3/2磷酸化表位。这是必不可少的，以允许招聘Cdc 20到独立的着丝粒和装配后期促进复合物/环体抑制复合物的水平，确保长期的SAC活性。我们提出了一个模型，其中波罗控制Mps 1依赖性BubR 1磷酸化，以促进Cdc 20动粒募集和持续的SAC功能。
Maintenance of genomic stability during eukaryotic cell division relies on the spindle assembly checkpoint (SAC) that prevents mitotic exit until all chromosomes are properly attached to the spindle. Polo is a mitotic kinase proposed to be involved in SAC function, but its role has remained elusive. We demonstrate that Polo and Aurora B functional interdependency comprises a positive feedback loop that promotes Mps1 kinetochore localization and activity. Expression of constitutively active Polo restores normal Mps1 kinetochore levels even after Aurora B inhibition, highlighting a role for Polo in Mps1 recruitment to unattached kinetochores downstream of Aurora B. We also show that Mps1 kinetochore localization is required for BubR1 hyperphosphorylation and formation of the 3F3/2 phosphoepitope. This is essential to allow recruitment of Cdc20 to unattached kinetochores and the assembly of anaphase-promoting complex/cyclosome-inhibitory complexes to levels that ensure long-term SAC activity. We propose a model in which Polo controls Mps1-dependent BubR1 phosphorylation to promote Cdc20 kinetochore recruitment and sustained SAC function.