Involvement of a centrosomal protein kendrin in the maintenance of centrosome cohesion by modulating Nek2A kinase activity.
Involvement of a centrosomal protein kendrin in the maintenance of centrosome cohesion by modulating Nek2A kinase activity.
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DOI：
10.1016/j.bbrc.2010.06.063
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发表时间：
2010-07
影响因子：
3.1
通讯作者：
K. Matsuo;Tamako Nishimura;Akihide Hayakawa;Y. Ono;Mikiko Takahashi
中科院分区：
文献类型：
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作者：
K. Matsuo;Tamako Nishimura;Akihide Hayakawa;Y. Ono;Mikiko Takahashi
中心体周期与染色体复制周期严格协调，以保证染色体的忠实分离。中心体复制发生在S期开始时，复制的中心体通过中心体内聚作用结合在一起，在间期作为单个微管组织中心发挥作用。在G2期晚期，中心体凝聚力被Nek2A激酶介导的磷酸化分解，因此，中心体分裂并构成有丝分裂中的纺锤体极。有报道称，中心体蛋白Kendrin（也称为pericentrin）的缺失会导致中心体在间期过早分裂，然而，Kendrin如何维持中心体的凝聚力仍不清楚。在这里，我们表明，肯德拉协会与Nek2A激酶，表现出相当低的活性。Nek2A激酶活性在体外通过以剂量依赖性方式添加Kendrin的Nek2A结合区域而被抑制。此外，同一区域的异位表达减少了G2期晚期中心体分裂的细胞数量。两者合计，这些结果表明，kendrin锚定Nek2A和抑制其激酶活性的中心体，因此，参与的机制，以防止过早的中心体分裂间期。
Centrosome cycle is strictly coordinated with chromosome duplication cycle to ensure the faithful segregation of chromosomes. Centrosome duplication occurs from the beginning of S phase, and the duplicated centrosomes are held together by centrosome cohesion to function as a single microtubule organizing center during interphase. At late G2 phase centrosome cohesion is disassembled by Nek2A kinase-mediated phosphorylation and, as a consequence, centrosomes are split and constitute spindle poles in mitosis. It has been reported that depletion of a centrosomal protein kendrin (also named pericentrin) induces premature centrosome splitting in interphase, however, it remains unknown how kendrin contributes to the maintenance of centrosome cohesion. Here we show that kendrin associates with Nek2A kinase, which exhibits considerably low activity. Nek2A kinase activity is inhibited in vitro by addition of the Nek2A-binding region of kendrin in a dose-dependent manner. Furthermore, ectopic expression of the same region decreases the number of the cells with split centrosomes at late G2 phase. Taken together, these results suggest that kendrin anchors Nek2A and suppresses its kinase activity at the centrosomes, and thus, is involved in the mechanism to prevent premature centrosome splitting during interphase.