NuSAP is degraded by APC/C-Cdh1 and its overexpression results in mitotic arrest dependent of its microtubules' affinity
NuSAP is degraded by APC/C-Cdh1 and its overexpression results in mitotic arrest dependent of its microtubules' affinity
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NuSAP 被 APC/C-Cdh1 降解，其过度表达导致有丝分裂停滞，这取决于其微管的亲和力。
DOI：
10.1016/j.cellsig.2007.05.017
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发表时间：
2007-10-01
影响因子：
4.8
通讯作者：
He, Fuchu
中科院分区：
文献类型：
--
作者：
Li, Lu;Zhou, Ying;He, Fuchu
微管相关蛋白参与微管动力学的调节。它的突变和失调导致严重的后果，如有丝分裂阻滞和凋亡。NuSAP已被报道为微管相关蛋白，其通过RNAi的消耗导致纺锤体缺陷和胞质分裂失败。然而，其在细胞周期调控中的作用以及NuSAP蛋白在细胞周期进程中如何被控制仍不清楚。在这里，我们表明，NuSAP可以泛素化和APC/C-hCdh 1 E3连接酶降解。进化上保守的KEN盒作为NuSAP的降解决定子发挥作用。NuSAP的过表达诱导有丝分裂阻滞，并且微管相关结构域和核定位都是NuSAP诱导有丝分裂阻滞所需的。此外，NuSAP的过表达导致细胞积聚，微管成束和纺锤体缺陷。因此，我们的研究结果第一次证明，NuSAP蛋白水平是由APC/C泛素连接酶复合物和NuSAP诱导有丝分裂阻滞依赖于其微管亲和力的紧密调控。(c)2007年爱思唯尔公司All rights reserved.
Microtubule associated proteins are involved in regulation of microtubule dynamics. Its mutation and dysregulation result in severe consequences such as mitotic block and apoptosis. NuSAP has been reported as a microtubule associated protein, depletion of which by RNAi results in spindle deficiency and cytokinesis failure. However, its role in regulation of cell cycle and how NuSAP protein is controlled during cell cycle progression still remains unclear. Here we show that NuSAP can be ubiquitinated and degraded by APC/C-hCdh1 E3 ligase. Evolutionally conserved KEN box functions as the degron of NuSAP. Overexpression of NuSAP induces mitotic arrest and the microtubule associated domain and nuclear localization are both required for NuSAP to induce mitotic arrest. Furthermore, overexpression of NuSAP results in cells accumulation with microtubule bundling and spindle deficiency. Thus, our results give evidence for the first time that NuSAP protein level is tightly regulated by the APC/C ubiquitin ligase complex and NuSAP induces mitotic arrest dependent of its microtubule affinity. (c) 2007 Elsevier Inc. All rights reserved.