NAT10, a nucleolar protein, localizes to the midbody and regulates cytokinesis and acetylation of microtubules
NAT10, a nucleolar protein, localizes to the midbody and regulates cytokinesis and acetylation of microtubules
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DOI：
10.1016/j.yexcr.2009.03.007
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发表时间：
2009-06-10
影响因子：
3.7
通讯作者：
Zhang, Bo
中科院分区：
文献类型：
--
作者：
Shen, Qi;Zheng, Xingzheng;Zhang, Bo
中体是有丝分裂后期形成的结构细胞器，负责细胞质分裂的完成。虽然已经发现各种各样的蛋白质分布或迁移到这个细胞器，但它们的功能仍然没有完全弄清楚。在本研究中，我们证明了NAT10 （N-acetyltransferase 10, NAT10）不仅在间期主要分布在核仁中，而且在末期也集中在有丝分裂的中间体中。NAT10 n端549-834结构域特异性介导其亚细胞定位。基因毒性药物或辐照处理可增加核仁和中体的NAT10浓度。此外，DNA损伤诱导的中体NAT10的升高明显伴随着乙酰化α -微管蛋白水平的原位升高，提示其具有维持或增强α -微管蛋白稳定性的作用。NAT10的缺失导致核仁组装缺陷、细胞分裂和乙酰化α -微管蛋白减少，导致G2/M细胞周期停滞或有丝分裂退出延迟。此外，NAT10在多种软组织肉瘤中均存在过表达，且与肿瘤组织学分级相关。这些结果表明，NAT10可能通过促进细胞有丝分裂后期核仁和中间体的重组以及微管的稳定，在细胞分裂中发挥重要作用。(C) 2009爱思唯尔公司版权所有。
The midbody is a structural organelle formed in late phase mitosis which is responsible for completion of cytokinesis. Although various kinds of proteins have been found to distribute or immigrate to this organelle, their functions have still not been completely worked out. In this study, we demonstrated that NAT10 (N-acetyltransferase 10, NAT10) is not only predominantly distributed in the nucleolus in interphase, but is also concentrated in the mitotic midbody during telophase. The domain in N-terminal residues 549-834 of NAT10 specifically mediated its subcellular localization. Treatment with genotoxic agents or irradiation increased concentration of NAT10 in both the nucleolus and midbody. Moreover, DNA damage induced increase of NAT10 in the midbody apparently accompanied by in situ elevation of the level of acetylated alpha-tubulin, suggesting that it plays a role in maintaining or enhancing stability of alpha-tubulin. The depletion of NAT10 induced defects in nucleolar assembly, cytokinesis and decreased acetylated alpha-tubulin, leading to G2/M cell cycle arrest or delay of mitotic exit. In addition, over-expression of NAT10 was found in a variety of soft tissue sarcomas, and correlated with tumor histological grading. These results indicate that NAT10 may play an important role in cell division through facilitating reformation of the nucleolus and midbody in the late phase of cell mitosis, and stabilization of microtubules. (C) 2009 Elsevier Inc. All rights reserved.