Aurora-C Interactions with Survivin and INCENP Reveal Shared and Distinct Features Compared with Aurora-B Chromosome Passenger Protein Complex.
Aurora-C Interactions with Survivin and INCENP Reveal Shared and Distinct Features Compared with Aurora-B Chromosome Passenger Protein Complex.
复制标题
与Aurora-B染色体载客蛋白复合物相比，Aurora-C与Survivin和Incenp的相互作用揭示了共享和独特的特征。
DOI：
10.1371/journal.pone.0157305
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Sen S
中科院分区：
文献类型：
--
作者：
Sasai K;Katayama H;Hawke DH;Sen S
Aurora-C是Aurora-B家族中的一员，在有丝分裂中可以补充Aurora-B的功能，在大多数成体组织中适度表达或抑制，但在早期胚胎发育中活跃，在多种人类癌症中高水平表达。据报道，Aurora-C的过度表达在肿瘤的发生转化中发挥了作用。我们参照已知的Aurora-B相互作用，对Aurora-C与染色体乘客复合体(CPC)、Survivin和内着丝粒蛋白(INCENP)成员的相互作用进行了详细的表征，以了解Aurora-C在人类癌细胞中过表达的功能意义。结果表明，单独沉默Aurora-C或-B并不影响另一种激酶的定位，这两种激酶在体内主要存在于独立的复合体中。Aurora-C和-B在不同大小的分子复合体中的存在，以及在INCENP过表达细胞中的重叠和共存，表明体内不同生理条件下三元复合体的齐聚。此外，Aurora-C和-B通过与IN box结构域的相互作用和磷酸化来稳定INCENP，而Aurora-C在Survivin丝氨酸20上的磷酸化后被激活。Aurora-C和-B对Survivin残基丝氨酸20的磷酸化似乎对适当的染色体分离很重要。综上所述，我们的研究表明，在体细胞中低水平表达的Aurora-C通过有丝分裂与Aurora-B一起作为CPC的催化成分发挥作用。癌细胞中Aurora-C的高表达改变了Aurora-B-CPC的结构和功能特征，导致染色体不稳定。
Aurora-C, a member of the Aurora kinase family that can complement Aurora-B function in mitosis is either moderately expressed or repressed in most adult somatic tissues but is active in early embryonic development and expressed at elevated levels in multiple human cancers. Aurora-C overexpression reportedly plays a role in tumorigenic transformation. We performed detailed characterization of Aurora-C interactions with members of the Chromosome Passenger Complex (CPC), Survivin and Inner Centromere Protein (INCENP) in reference to known Aurora-B interactions to understand the functional significance of Aurora-C overexpression in human cancer cells. The results revealed that silencing of Aurora-C or -B individually does not affect localization of the other kinase and the two kinases exist predominantly in independent complexes in vivo. Presence of Aurora-C and -B in molecular complexes of varying as well as overlapping sizes and co-existence in INCENP overexpressing cells indicated oligomerization of ternary complexes under different physiological conditions in vivo. Furthermore, Aurora-C and -B stabilized INCENP through interaction with and phosphorylation of the IN box domain while Aurora-C was activated following Survivin phosphorylation on Serine 20. Phosphorylation of Survivin residue Serine 20 by Aurora-C and –B appears important for proper chromosome segregation. Taken together, our study suggests that Aurora-C, expressed at low levels in somatic cells, functions as a catalytic component of the CPC together with Aurora-B through mitosis. Elevated expression of Aurora-C in cancer cells alters the structural and functional characteristics of the Aurora-B-CPC leading to chromosomal instability.