Mad2 promotes Cyclin B2 recruitment to the kinetochore for guiding accurate mitotic checkpoint
Mad2 promotes Cyclin B2 recruitment to the kinetochore for guiding accurate mitotic checkpoint
复制标题
Mad2 促进 Cyclin B2 募集至着丝粒，以指导准确的有丝分裂检查点
DOI：
10.15252/embr.202154171
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发表时间：
2022-04-05
期刊：
影响因子：
7.7
通讯作者：
Liu, Xing
中科院分区：
文献类型：
--
作者：
Liu, Sikai;Yuan, Xiao;Liu, Xing
准确的有丝分裂进程依赖于关键有丝分裂激酶对多种底物的动态磷酸化。细胞周期蛋白依赖性激酶1是协调有丝分裂进程的主激酶，需要其调节亚基细胞周期蛋白B来确保完全的激酶活性和底物特异性。细胞周期蛋白B2是细胞周期蛋白B1的一个密切相关的家族成员，其功能在很大程度上仍然是难以捉摸的。在这里，我们表明，Mad 2促进细胞周期蛋白B2的动粒定位，它们在动粒的相互作用指导准确的染色体分离。我们的生化分析的特点是Mad 2-细胞周期蛋白B2的相互作用，并描绘了一个新的Mad 2相互作用的基序（MIM）细胞周期蛋白B2。通过实时成像证实了细胞周期蛋白B2-Mad 2相互作用的功能重要性，其中MIM缺陷型突变细胞周期蛋白B2未能挽救染色体分离缺陷。两者合计，我们已经划定了一个以前未定义的功能，细胞周期蛋白B2在动粒，并已建立，在人类细胞中，一种机制的行动，Mad 2有助于纺锤体检查点。
Accurate mitotic progression relies on the dynamic phosphorylation of multiple substrates by key mitotic kinases. Cyclin-dependent kinase 1 is a master kinase that coordinates mitotic progression and requires its regulatory subunit Cyclin B to ensure full kinase activity and substrate specificity. The function of Cyclin B2, which is a closely related family member of Cyclin B1, remains largely elusive. Here, we show that Mad2 promotes the kinetochore localization of Cyclin B2 and that their interaction at the kinetochores guides accurate chromosome segregation. Our biochemical analyses have characterized the Mad2-Cyclin B2 interaction and delineated a novel Mad2-interacting motif (MIM) on Cyclin B2. The functional importance of the Cyclin B2-Mad2 interaction was demonstrated by real-time imaging in which MIM-deficient mutant Cyclin B2 failed to rescue the chromosomal segregation defects. Taken together, we have delineated a previously undefined function of Cyclin B2 at the kinetochore and have established, in human cells, a mechanism of action by which Mad2 contributes to the spindle checkpoint.