A novel role for TPX2 as a scaffold and co-activator protein of the Chromosomal Passenger Complex.
A novel role for TPX2 as a scaffold and co-activator protein of the Chromosomal Passenger Complex.
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DOI：
10.1016/j.cellsig.2012.04.014
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发表时间：
2012-08
影响因子：
4.8
通讯作者：
Tsai MY
中科院分区：
文献类型：
--
作者：
Iyer J;Tsai MY
极光B激酶形成染色体乘客复合物（CPC）的酶核心，并且是有丝分裂的主要调节剂。了解Aurora B的调控对于阐明其在有丝分裂中的作用至关重要。INCENP、Survivin和Borealin都已知促进Aurora B活化。在这项研究中，我们已经确定了极光A激活蛋白TPX 2作为一种新的支架和共激活蛋白的CPC。利用M期非洲爪蟾卵提取物（XEE）的研究揭示，来自XEE的内源性TPX 2的免疫耗竭降低极光B-Survivin和极光B-INCENP相互作用，导致极光B活性的随之降低。此外，非洲爪蟾TPX 2（TPX 2 B）的残基138至328足以在体外增强极光B-存活蛋白缔合和极光B激酶活性。重要的是，胰腺癌细胞系的实验表明，TPX 2激活Aurora B的这种机制可能在人类细胞中是保守的。引人注目的是，人TPX 2 B在HeLa细胞中的过表达导致中期染色体比对和INCENP定位的缺陷。因此，除了已经确定的作为极光A激活剂的作用之外，我们的数据支持TPX 2作为极光激酶B的新型共激活剂的作用。
Aurora B kinase forms the enzymatic core of the Chromosomal Passenger Complex (CPC) and is a master regulator of mitosis. Understanding the regulation of Aurora B is critical to illuminate its role in mitosis. INCENP, Survivin and Borealin have all been known to promote Aurora B activation. In this study, we have identified the Aurora A activator protein TPX2 as a novel scaffold and co-activator protein of the CPC. Studies utilizing M-phase Xenopus egg extracts (XEE) revealed that the immunodepletion of endogenous TPX2 from XEE decreases Aurora B-Survivin and Aurora B-INCENP interactions, leading to a consequent reduction in Aurora B activity. Further, residues 138 to 328 of Xenopus TPX2 (TPX2 B) are sufficient to enhance Aurora B-Survivin association and Aurora B kinase activity in vitro. Importantly, experiments with pancreatic cancer cell lines suggest that this mechanism of Aurora B activation by TPX2 is likely to be conserved in human cells. Strikingly, the overexpression of human TPX2 B in HeLa cells causes defects in metaphase chromosome alignment and INCENP localization. Thus, in addition to its already established role as an Aurora A activator, our data support the role of TPX2 as a novel co-activator of Aurora kinase B.
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DOI：
10.1016/j.bbagrm.2010.09.004
发表时间：
2010-10
期刊：
Biochimica et biophysica acta
影响因子：
--
作者：
Katayama H;Sen S
通讯作者：
Sen S
影响因子：
7.5
作者：
Carmena M;Ruchaud S;Earnshaw WC
通讯作者：
Earnshaw WC
影响因子：
19
作者：
Adams, RR;Carmena, M;Earnshaw, WC
通讯作者：
Earnshaw, WC
影响因子：
4
作者：
Jacob NK;Cooley JV;Shirai K;Chakravarti A
通讯作者：
Chakravarti A
DOI：
10.1083/jcb.200404001
发表时间：
2004-07-19
期刊：
The Journal of cell biology
影响因子：
--
作者：
Gassmann R;Carvalho A;Henzing AJ;Ruchaud S;Hudson DF;Honda R;Nigg EA;Gerloff DL;Earnshaw WC
通讯作者：
Earnshaw WC