A novel role for TPX2 as a scaffold and co-activator protein of the Chromosomal Passenger Complex.

Cellular Signalling
Jyoti Iyer, Ming-Ying Tsai

Abstract

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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Citations

Sep 6, 2013·Journal of Experimental Botany·Beáta PetrovskáPavla Binarová
Feb 22, 2014·Cellular and Molecular Life Sciences : CMLS·Gernot NeumayerMinh Dang Nguyen
Jun 4, 2013·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Hong-Chun LiuChang-Lian Zhu
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Jul 18, 2019·American Journal of Physiology. Cell Physiology·Shao-Chih ChiuChang-Tze Ricky Yu
Mar 12, 2020·Cell Reports·Julia RohrbergAndrei Goga

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