Functional importance of the anaphase-promoting complex-Cdh1-mediated degradation of TMAP/CKAP2 in regulation of spindle function and cytokinesis
Functional importance of the anaphase-promoting complex-Cdh1-mediated degradation of TMAP/CKAP2 in regulation of spindle function and cytokinesis
复制标题
DOI：
10.1128/mcb.01386-06
复制
发表时间：
2007-05-01
影响因子：
5.3
通讯作者：
Park, Joobae
中科院分区：
文献类型：
--
作者：
Hong, Kyung Uk;Park, Young Soo;Park, Joobae
细胞凋亡相关蛋白2（CKAP 2），又称肿瘤相关微管相关蛋白（TMAP），是一种新的微管相关蛋白，在多种恶性肿瘤中表达上调。然而，其细胞功能仍然未知。先前的研究表明，其蛋白质水平在G（1）/S期间开始增加，并在G（2）/M达到峰值，之后突然下降。TMAP/CKAP 2的异位过表达诱导与增加微管稳定性相关的微管成束。TMAP/CKAP 2过表达也导致有丝分裂期间细胞周期停滞，这是由于中心体分离缺陷和随后单极纺锤体的形成。我们还表明，在有丝分裂退出TMAP/CKAP 2的降解介导的后期促进复合物绑定到Cdh 1和KEN盒基序附近的N端是必要的，其破坏。与野生型相比，TMAP/CKAP 2的非降解突变体的表达显著增加了纺锤体缺陷和胞质分裂失败的发生。这些结果表明，TMAP/CKAP 2在有丝分裂纺锤体的组装和维持中起作用，可能是通过调节微管动力学，并且在有丝分裂退出期间其破坏在胞质分裂的完成和在下一次有丝分裂中纺锤体双极性的维持中起重要作用。
Cytoskeleton-associated protein 2 (CKAP2), also known as tumor-associated microtubule-associated protein (TMAP), is a novel microtubule-associated protein that is frequently upregulated in various malignances. However, its cellular functions remain unknown. A previous study has shown that its protein level begins to increase during G(1)/S and peaks at G(2)/M, after which it decreases abruptly. Ectopic overexpression of TMAP/CKAP2 induced microtubule bundling related to increased microtubule stability. TMAP/CKAP2 overexpression also resulted in cell cycle arrest during mitosis due to a defect in centrosome separation and subsequent formation of a monopolar spindle. We also show that degradation of TMAP/CKAP2 during mitotic exit is mediated by the anaphase-promoting complex bound to Cdh1 and that the KEN box motif near the N terminus is necessary for its destruction. Compared to the wild type, expression of a nondegradable mutant of TMAP/CKAP2 significantly increased the occurrence of spindle defects and cytokinesis failure. These results suggest that TMAP/CKAP2 plays a role in the assembly and maintenance of mitotic spindles, presumably by regulating microtubule dynamics, and its destruction during mitotic exit serves an important role in the completion of cytokinesis and in the maintenance of spindle bipolarity in the next mitosis.