Oshimori Naoki, Ohsugi Miho, Yamamoto Tadashi
Division of Oncology, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
Nat Cell Biol. 2006 Oct;8(10):1095-101. doi: 10.1038/ncb1474. Epub 2006 Sep 17.
Formation of a bipolar spindle is essential for faithful chromosome segregation at mitosis. Because centrosomes define spindle poles, defects in centrosome number and structural organization can lead to a loss of bipolarity. In addition, microtubule-mediated pulling and pushing forces acting on centrosomes and chromosomes are also important for bipolar spindle formation. Polo-like kinase 1 (Plk1) is a highly conserved Ser/Thr kinase that has essential roles in the formation of a bipolar spindle with focused poles. However, the mechanism by which Plk1 regulates spindle-pole formation is poorly understood. Here, we identify a novel centrosomal substrate of Plk1, Kizuna (Kiz), depletion of which causes fragmentation and dissociation of the pericentriolar material from centrioles at prometaphase, resulting in multipolar spindles. We demonstrate that Kiz is critical for establishing a robust mitotic centrosome architecture that can endure the forces that converge on the centrosomes during spindle formation, and suggest that Plk1 maintains the integrity of the spindle poles by phosphorylating Kiz.
双极纺锤体的形成对于有丝分裂时染色体的准确分离至关重要。由于中心体决定纺锤体极，中心体数量和结构组织的缺陷会导致双极性的丧失。此外，作用于中心体和染色体的微管介导的拉力和推力对于双极纺锤体的形成也很重要。Polo样激酶1（Plk1）是一种高度保守的丝氨酸/苏氨酸激酶，在形成具有聚焦极的双极纺锤体中起重要作用。然而，Plk1调节纺锤体极形成的机制尚不清楚。在这里，我们鉴定出Plk1的一种新的中心体底物Kizuna（Kiz），其缺失会导致前中期中心粒周围物质从中心粒碎片化和解离，从而产生多极纺锤体。我们证明Kiz对于建立一个强大的有丝分裂中心体结构至关重要，该结构能够承受纺锤体形成过程中汇聚在中心体上的力，并表明Plk1通过磷酸化Kiz来维持纺锤体极的完整性。
