Kim Seul, Jang Chang-Young
Research Center for Cell Fate Control, College of Pharmacy, Sookmyung Women's University, Seoul 140-742, Republic of Korea.
Research Center for Cell Fate Control, College of Pharmacy, Sookmyung Women's University, Seoul 140-742, Republic of Korea.
Biochem Biophys Res Commun. 2016 Feb 12;470(3):484-491. doi: 10.1016/j.bbrc.2016.01.144. Epub 2016 Jan 25.
Spindle dynamics drives chromosome movement and mitotic progression during mitosis. Microtubule (MT)-associated proteins (MAPs) regulate MT stabilization/destabilization and MT polymerization/depolymerization for congression of sister chromatids at the mitotic equator and subsequent segregation toward the spindle poles. Here, we identified ANKRD53 as a novel DDA3-interacting protein through proteomic analysis. Based on expression profiles, ANKRD53 is phosphorylated by mitotic kinases during mitosis. In ANKRD53-depleted HeLa cells, the progression of mitosis was delayed and the number of unaligned chromosomes increased substantially. In addition, spindle MT polymerization decreased and the spindle assembly checkpoint (SAC) was concomitantly activated by the decreased spindle dynamics in ANKRD53-depleted cells. Although ANKRD53 is recruited to the mitotic spindle by DDA3, it counteracts the activity of DDA3 for spindle MT polymerization. Furthermore, ANKRD53 depletion increased the number of bi-nuclei and polylobed nuclei. Thus, ANKRD53 is recruited to the mitotic spindle by DDA3 and acts as a regulator of spindle dynamics and cytokinesis.
纺锤体动力学在有丝分裂过程中驱动染色体运动和有丝分裂进程。微管（MT）相关蛋白（MAPs）调节MT的稳定/不稳定以及MT的聚合/解聚，以使姐妹染色单体在有丝分裂赤道板处汇聚，并随后向纺锤体极分离。在此，我们通过蛋白质组学分析鉴定ANKRD53为一种新型的与DDA3相互作用的蛋白。基于表达谱，ANKRD53在有丝分裂期间被有丝分裂激酶磷酸化。在ANKRD53缺失的HeLa细胞中，有丝分裂进程延迟，未排列的染色体数量大幅增加。此外，纺锤体MT聚合减少，并且在ANKRD53缺失的细胞中，纺锤体动力学降低，纺锤体组装检查点（SAC）随之被激活。尽管ANKRD53通过DDA3被招募到有丝分裂纺锤体，但它会抵消DDA3对纺锤体MT聚合的活性。此外，ANKRD53缺失增加了双核和多叶核的数量。因此，ANKRD53通过DDA3被招募到有丝分裂纺锤体，并作为纺锤体动力学和胞质分裂的调节因子发挥作用。
