RACK1 通过调节 Aurora-A 影响 G2/M 的进程。
RACK1 affects the progress of G2/M by regulating Aurora-A.
机构信息
State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University , Shanghai , P. R. China.
Department Oncology, Hutchison Medi Pharma , Shanghai , China.
出版信息
Cell Cycle. 2019 Sep;18(18):2228-2238. doi: 10.1080/15384101.2019.1642065. Epub 2019 Jul 29.
Abstract
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.
摘要
极光激酶 A 是一种丝氨酸/苏氨酸激酶，在多种人类癌症中过度表达，在肿瘤发生和发展中发挥关键作用。在这项研究中，我们发现，激活的 C 激酶 1 受体（RACK1），一种重要的生物学功能调节剂，与极光激酶 A 相互作用，并与极光激酶 A 在中心体中共定位。此外，RACK1 诱导极光激酶 A 在体外和体内的自动磷酸化。RACK1 的耗竭会损害晚期 G2 期极光激酶 A 的激活，然后抑制有丝分裂进入，并导致多极、严重的染色体排列缺陷或中心体扩增。总之，这些结果表明，RACK1 是极光激酶 A 的一个新伴侣，在有丝分裂期间调节极光激酶 A 的活性中发挥关键作用，这可能为未来针对极光激酶 A 的抗癌研究提供基础。
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