Graduate School of Science, Kobe University, 1-1 Rokkodai-cho, Nada-ku, Kobe 657-8501, Japan.
Biochem Biophys Res Commun. 2010 Jul 23;398(2):217-23. doi: 10.1016/j.bbrc.2010.06.063. Epub 2010 Jun 18.
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.
中心体周期与染色体复制周期严格协调，以确保染色体的准确分离。中心体复制始于 S 期开始，复制的中心体通过中心体黏合保持在一起，在间期作为单个微管组织中心发挥作用。在 G2 期晚期，中心体黏合通过 Nek2A 激酶介导的磷酸化而解聚，因此，中心体分裂并在有丝分裂中构成纺锤体极。据报道，中心体蛋白 kendrin（也称为中心粒蛋白）的耗竭会导致间期中心体过早分裂，然而，kendrin 如何有助于维持中心体黏合仍不清楚。在这里，我们表明 kendrin 与 Nek2A 激酶结合，后者表现出相当低的活性。Nek2A 激酶活性在体外被 kendrin 的 Nek2A 结合区域以剂量依赖性方式抑制。此外，相同区域的异位表达可减少晚期 G2 期具有分裂中心体的细胞数量。总之，这些结果表明，kendrin 锚定 Nek2A 并抑制其在中心体的激酶活性，从而参与防止间期过早中心体分裂的机制。
