Department of Biochemistry and Molecular Biology and Tulane Center for Aging, Tulane University Health Sciences Center, New Orleans, LA, 70112, USA.
Bioessays. 2018 Mar;40(3). doi: 10.1002/bies.201700176. Epub 2018 Jan 23.
The human spindle and kinetochore associated (Ska) complex is required for proper mitotic progression. Extensive studies have demonstrated its important functions in both stable kinetochore-microtubule interactions and spindle checkpoint silencing. We suggest a model to explain how various Ska functions might be fulfilled by distinct pools of Ska at kinetochores. The Ndc80-loop pool of Ska is recruited by the Ndc80 loop, or together with some of its flanking sequences, and the recruitment is also dependent on Cdk1-mediated Ska3 phosphorylation. This pool seems to play a more important role in silencing the spindle checkpoint than stabilizing kinetochore-microtubule interactions. In contrast, the Ndc80-N-terminus pool of Ska is recruited by the N-terminal domains of Ndc80 and appears to be more important for stabilizing kinetochore-microtubule interactions. Here, we review and discuss the evidence that supports this model and suggest further experiments to test the functioning mechanisms of the Ska complex.
人类纺锤体和着丝粒相关（Ska）复合物对于有丝分裂的正常进行是必需的。大量研究已经证明了它在稳定的着丝粒微管相互作用和纺锤体检查点沉默中的重要功能。我们提出了一个模型来解释不同的 Ska 功能如何通过不同的 Ska 池在着丝粒上得到满足。Ska 的 Ndc80 环池被 Ndc80 环募集，或者与它的一些侧翼序列一起被募集，募集也依赖于 Cdk1 介导的 Ska3 磷酸化。这个池似乎在沉默纺锤体检查点方面比稳定着丝粒微管相互作用更为重要。相比之下，Ska 的 Ndc80-N 端池被 Ndc80 的 N 端结构域募集，并且似乎在稳定着丝粒微管相互作用方面更为重要。在这里，我们回顾并讨论了支持这一模型的证据，并提出了进一步的实验来测试 Ska 复合物的作用机制。
