RACK1 affects the progress of G2/M by regulating Aurora-A
RACK1 affects the progress of G2/M by regulating Aurora-A
复制标题
RACK1通过调节Aurora-A影响G2/M的进程
DOI：
10.1080/15384101.2019.1642065
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发表时间：
2019-07-31
期刊：
影响因子：
4.3
通讯作者：
Bai, Meirong
中科院分区：
文献类型：
--
作者：
Shen, Suqin;Feng, Huan;Bai, Meirong
Aurora-A是一种丝氨酸/苏氨酸激酶，在多种人类癌症中过表达，在肿瘤发生和肿瘤发展中起关键作用。在本研究中，我们发现，活化的C-激酶1受体（RACK 1），一个重要的生物学功能的调节器，与Aurora-A相互作用，并与Aurora-A共定位在中心体。此外，RACK 1在体外和体内诱导Aurora-A的自磷酸化。RACK 1缺失可导致Aurora-A在G2晚期的激活减弱，进而抑制有丝分裂进入，导致多极化、严重的染色体排列缺陷或中心体扩增。综上所述，这些结果表明RACK 1是Aurora-A的新伴侣，在有丝分裂过程中调节Aurora-A的活性中发挥关键作用，这可能为未来针对Aurora-A的抗癌研究提供基础。
Aurora-A is a serine/threonine kinase, which is overexpressed in multiple human cancers and plays a key role in tumorigenesis and tumor development. In this study, we found that the receptor of activated C-kinase1 (RACK1), an important regulator of biological functions, interacted with Aurora-A and co-localized with Aurora-A at centrosomes. Moreover, RACK1 induces the auto-phosphorylation of Aurora-A in vitro and in vivo. Depletion of RACK1 impaired the activation of Aurora-A in late G2 phase, then inhibited the mitotic entry and leaded to multi-polarity, severe chromosome alignment defects, or centrosome amplification. Taken together, these results suggest that RACK1 is a new partner of Aurora-A and play a critical role in the regulation of the Aurora-A activity during mitosis, which may provide a basis for future anticancer studies targeting Aurora-A.