Cdh1 controls the stability of TACC3
Cdh1 controls the stability of TACC3
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DOI：
10.4161/cc.8.21.9935
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发表时间：
2009-11-01
期刊：
影响因子：
4.3
通讯作者：
Shih, Hsiu-Ming
中科院分区：
文献类型：
--
作者：
Jeng, Jen-Chong;Lin, Ying-Mei;Shih, Hsiu-Ming
转化酸性卷曲螺旋蛋白3（TACC 3）被报道在调节有丝分裂纺锤体组装和染色体分离中起重要作用。虽然TACC 3的蛋白质水平在细胞周期进程中显示出改变，但控制TACC 3水平的分子机制尚不清楚。在这里，我们表明，TACC 3蛋白水平可以调节Cdh 1，一个众所周知的后期促进复合物/环体的激活剂。我们通过酵母阵列筛选确定Cdh 1为TACC 3的相互作用伴侣。体外和体内结合研究表明，TACC 3可以与Cdh 1形成复合物。内源性Cdh 1的耗尽延长了有丝分裂退出期间的TACC 3蛋白水平。异位过表达或siRNA敲低Cdh 1水平的改变分别与泛素化TACC 3的增加或减少密切相关。此外，TACC 3的结构域定位研究显示，多个结构域参与Cdh 1调节的TACC 3降解。总之，我们的研究结果表明，Cdh 1控制TACC 3蛋白的稳定性在有丝分裂退出。
Transforming acidic coiled-coil protein 3 (TACC3) was reported to be important for regulating mitotic spindle assembly and chromosome segregation. While the protein level of TACC3 was shown to be altered during cell cycle progression, the molecular mechanism in controlling TACC3 level is unclear. Here, we show that TACC3 protein level can be regulated by Cdh1, a well known activator of anaphase-promoting complex/cyclosome. We identified Cdh1 as an interacting partner of TACC3 by a yeast array screen. Both in vitro and in vivo binding studies indicated that TACC3 can form complexes with Cdh1. Depletion of endogenous Cdh1 prolonged TACC3 protein level during mitotic exit. Alteration of Cdh1 level by ectopic overexpression or siRNA knockdown correlated well with an increase or decrease of ubiquitinated TACC3, respectively. Furthermore, the domain mapping studies of TACC3 revealed that multiple domains are involved in Cdh1-regulated degradation of TACC3. Altogether, our findings suggest that Cdh1 controls TACC3 protein stability during mitotic exit.