Functional analysis of separase and its novel substrate in the licensing of centrosome duplication

中心体在有丝分裂期间组装双极纺锤体，以确保复制染色体的平等分离。因此，假设许可机制严格调节中心体复制的起始，每个细胞周期只有一次，尽管精确的过程在很大程度上仍然未知。分离酶，一种触发姐妹染色单体分离的半胱氨酸蛋白酶，已知参与了这种许可，然而，其中心体底物仍未确定。在这项研究中，我们发现中心体蛋白kendrin在一个共识位点被分离酶切割。此外，不可切割的kendrin突变体的表达抑制中心体复制的开始。我们的发现提供了第一个证据，证明kendrin是中心体上参与中心体复制许可的分离酶的一种新的和关键的底物。

Centrosome assembles the bipolar spindle during mitosis to ensure the equal segregation of replicated chromosomes. It is thereby assumed that the licensing mechanism tightly regulates the initiation of centrosome duplication only once per cell cycle, though precise process remains largely unknown. Separase, a cysteine protease that triggers sister chromatid separation, is known to be involved in this licensing, however, its centrosomal substrate remains unidentified. In this study, we found that the centrosomal protein kendrin is cleaved by separase at a consensus site. Moreover, expression of a non-cleavable kendrin mutant suppresses the initiation of centrosome duplication. Our finding provides the first evidence that kendrin is a novel and crucial substrate for separase at the centrosome involved in the licensing of centrosome duplication.