Program in Cancer and Stem Cell Biology, Graduate Medical School, Duke-National University of Singapore, 169857 Singapore.
J Cell Biol. 2010 Dec 13;191(6):1069-77. doi: 10.1083/jcb.201003095.
We identified the mitotic kinesin-like protein 2 (MKlp2), a kinesin required for chromosome passenger complex (CPC)-mediated cytokinesis, as a target of the mitotic checkpoint protein Mad2. MKlp2 possesses a consensus Mad2-binding motif required for Mad2 binding. Mad2 prevents MKlp2 from loading onto the mitotic spindle, a prerequisite step for its function as a mitotic kinesin. Furthermore, Mad2 inhibits the ability of MKlp2 to relocate the CPC from centromeres, an essential step to promote cytokinesis. An MKlp2 mutant that is refractory to Mad2-mediated inhibition prematurely translocates to the mitotic spindle and mislocalizes the CPC component Aurora B from the midbody of dividing cells. This correlates with an increased incidence of cytokinesis failure. Together, these findings reveal that MKlp2 is a novel mitotic target of Mad2 necessary for proper mitotic progression and cytokinesis.
我们鉴定出有丝分裂驱动蛋白样蛋白 2（MKlp2）是细胞分裂染色体乘客复合物（CPC）介导所必需的驱动蛋白，也是有丝分裂检查点蛋白 Mad2 的靶标。MKlp2 具有 Mad2 结合所需的共识 Mad2 结合基序。Mad2 防止 MKlp2 加载到有丝分裂纺锤体上，这是其作为有丝分裂驱动蛋白功能的先决条件步骤。此外，Mad2 抑制了 MKlp2 将 CPC 从着丝粒重新定位的能力，这是促进细胞分裂的必要步骤。对 Mad2 介导的抑制有抗性的 MKlp2 突变体过早地易位到有丝分裂纺锤体，并将 CPC 成分 Aurora B 从正在分裂的细胞的中体错误定位。这与胞质分裂失败的发生率增加相关。总之，这些发现表明 MKlp2 是 Mad2 的一种新的有丝分裂靶标，对于正确的有丝分裂进展和胞质分裂是必需的。
