Aurora kinase A–Targeting protein for Xklp2 (TPX2) protein–protein interaction interface (Aurora A–TPX2 PPI)

The Aurora kinase A–Targeting protein for Xklp2 (TPX2) protein–protein interaction (PPI) interface is a pivotal regulatory hub in the cell cycle, specifically during mitosis. Aurora kinase A (AURKA) is a serine/threonine kinase that plays a central role in centrosome maturation and the assembly of the bipolar mitotic spindle. Its activity is strictly regulated by the binding of TPX2, which induces an active conformation in the kinase domain and protects the activating phosphorylation on Threonine 288 from phosphatases [1][2]. This interaction also ensures the precise localization of Aurora A to the spindle microtubules. In many human cancers, both Aurora A and TPX2 are overexpressed, driving uncontrolled cell proliferation and chromosomal instability, which makes this interface an attractive therapeutic target [3][4]. While traditional inhibitors target the ATP-binding pocket of Aurora A, targeting the Aurora A–TPX2 PPI interface offers a mechanism for allosteric inhibition that can achieve greater specificity, particularly in distinguishing Aurora A from the closely related Aurora B [5]. Disrupting the Aurora A–TPX2 complex leads to spindle defects, mitotic arrest, and apoptosis, providing a potent strategy for treating various solid and hematological malignancies. Sources: [1] Bayliss et al. (2003) Mol Cell; [2] Kufer et al. (2002) J Cell Biol; [3] Neumayer et al. (2014) Cell Mol Life Sci; [4] Burgess et al. (2011) Expert Opin Ther Targets; [5] Koleutou et al. (2017) Expert Opin Ther Targets.

Other names

Aurora A–TPX2 complexAURKA–TPX2 interfaceAurora A–TPX2 binding siteAurora A–TPX2 interaction

Allosteric inhibition of Aurora kinase A by disrupting its interaction with the activator TPX2, which prevents kinase activation, protects the kinase from dephosphorylation, and inhibits proper spindle localization [1][5].