Department of Biochemistry and Molecular Biology, Colorado State University, Fort Collins, CO 80525, U.S.A.
Essays Biochem. 2020 Sep 4;64(2):299-311. doi: 10.1042/EBC20190081.
The fidelity of chromosome segregation during mitosis is intimately linked to the function of kinetochores, which are large protein complexes assembled at sites of centromeric heterochromatin on mitotic chromosomes. These key "orchestrators" of mitosis physically connect chromosomes to spindle microtubules and transduce forces through these connections to congress chromosomes and silence the spindle assembly checkpoint. Kinetochore-microtubule attachments are highly regulated to ensure that incorrect attachments are not prematurely stabilized, but instead released and corrected. The kinase activity of the centromeric protein Aurora B is required for kinetochore-microtubule destabilization during mitosis, but how the kinase acts on outer kinetochore substrates to selectively destabilize immature and erroneous attachments remains debated. Here, we review recent literature that sheds light on how Aurora B kinase is recruited to both centromeres and kinetochores and discuss possible mechanisms for how kinase interactions with substrates at distinct regions of mitotic chromosomes are regulated.
有丝分裂过程中染色体分离的保真度与动粒的功能密切相关,动粒是在有丝分裂染色体着丝粒异染色质部位组装的大型蛋白质复合物。这些有丝分裂的关键“协调者”通过这些连接将染色体物理连接到纺锤体微管上,并传递力,使染色体聚集并沉默纺锤体组装检查点。动粒-微管附着受到高度调控,以确保不正确的附着不会过早稳定,而是释放并纠正。着丝粒蛋白 Aurora B 的激酶活性对于有丝分裂期间动粒-微管的去稳定化是必需的,但是激酶如何作用于外动粒底物以选择性地去稳定不成熟和错误的附着仍然存在争议。在这里,我们回顾了最近的文献,这些文献阐明了 Aurora B 激酶如何被招募到着丝粒和动粒上,并讨论了调节有丝分裂染色体不同区域的激酶与底物相互作用的可能机制。