Defects in chromosome congression and mitotic progression in KIF18A-deficient cells are partly mediated through impaired functions of CENP-E.
Defects in chromosome congression and mitotic progression in KIF18A-deficient cells are partly mediated through impaired functions of CENP-E.
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KIF18A 缺陷细胞中染色体会聚和有丝分裂进展的缺陷部分是通过 CENP-E 功能受损介导的。
DOI：
10.4161/cc.8.16.9366
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发表时间：
2009-08-15
期刊：
影响因子：
--
通讯作者：
Dai W
中科院分区：
文献类型：
--
作者：
Huang Y;Yao Y;Xu HZ;Wang ZG;Lu L;Dai W
KIF18A是一种分子马达，在脊椎动物细胞有丝分裂过程中，通过减弱中部的动粒振荡幅度来调节染色体的有序聚集。在此，我们报告了KIF18A缺失导致HeLa细胞有丝分裂停止，并伴随着染色体不对齐的存在。这类似于CENP-E功能受损所引起的表型，CENP-E也是有丝分裂纺锤体形成所必需的有丝分裂动素。我们进一步的分析表明，KIF18A的缺失导致了CENP-E的特异性下调。KIF18A沉默导致CENP-E的下调不是由于转录减少，而主要是由于蛋白质降解增强。免疫共沉淀显示KIF18A在有丝分裂过程中与CENP-E和BubR1发生物理相互作用。CENP-E野生型尾部结构域的异位表达，而不是相应的突变体，显著抑制了有丝分裂细胞中的染色体聚集缺陷。总之，我们的研究有力地表明，KIF18A缺失导致的染色体聚集缺陷至少部分是通过不稳定的动粒CENP-E介导的。
KIF18A, a molecular motor, is an essential component in the regulation of orderly chromosome congression by attenuation of the kinetochore oscillation amplitude at the midzone during mitosis in vertebrate cells. Here we report that KIF18A depletion resulted in mitotic arrest which was accompanied by the presence of unaligned chromosomes in HeLa cells. This resembles the phenotype induced by an impaired function of CENP-E, also a mitotic kinesin essential for the formation of the mitotic spindles. Our further analysis showed that KIF18A depletion caused specific downregulation of CENP-E. Downregulation of CENP-E as the result of KIF18A silencing was not due to reduced transcription but primarily due to the enhanced protein degradation. Co-immunoprecipitation revealed that KIF18A physically interacted with CENP-E and BubR1 during mitosis. Ectopic expression of the wild-type tail domain of CENP-E, but not a corresponding mutant, significantly suppressed chromosome congression defects in mitotic cells. Together, our studies strongly suggest that chromosome congression defects as the result of KIF18A depletion is at least in part mediated through destabilizing kinetochore CENP-E.
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共粒相关的蛋白质-E对于哺乳动物有丝分裂检查点至关重要，以防止由于单染色体损失而导致非整倍性。
影响因子：
7.8
作者：
Weaver, Beth A A;Bonday, Zahid Q;Putkey, Frances R;Kops, Geert J P L;Silk, Alain D;Cleveland, Don W
通讯作者：
Cleveland, Don W
影响因子：
64.5
作者：
Abrieu, A;Kahana, JA;Cleveland, DW
通讯作者：
Cleveland, DW
影响因子：
64.5
作者：
Mao, YH;Abrieu, A;Cleveland, DW
通讯作者：
Cleveland, DW
DOI：
10.1083/jcb.200802189
发表时间：
2008-05-05
期刊：
The Journal of cell biology
影响因子：
--
作者：
Kim Y;Heuser JE;Waterman CM;Cleveland DW
通讯作者：
Cleveland DW
影响因子：
3.3
作者：
Tanudji, M;Shoemaker, J;Schebye, XM
通讯作者：
Schebye, XM