Aurora kinase A-Targeting protein for Xklp2 complex (Aurora A-TPX2)

The Aurora kinase A-Targeting protein for Xklp2 (Aurora A-TPX2) complex is a functional unit, often described as an oncogenic holoenzyme, that is essential for the regulation of mitosis [4, 9]. Aurora kinase A (AURKA) is a serine/threonine kinase that controls centrosome maturation and spindle assembly, while TPX2 is a microtubule-associated protein that serves as its primary activator [3, 12]. Binding of TPX2 to the catalytic domain of Aurora A induces a conformational change that activates the kinase and protects it from dephosphorylation by protein phosphatase 1 (PP1) and proteasomal degradation [10, 13]. This interaction is highly specific to Aurora A, making it a distinct therapeutic target compared to the closely related Aurora B [3, 12]. In many human cancers, including pancreatic, breast, and ovarian cancers, both proteins are co-overexpressed, which promotes genomic instability, aneuploidy, and resistance to antimitotic drugs like taxanes [1, 11, 15]. Therapeutic strategies focus on small-molecule protein-protein interaction (PPI) inhibitors, such as CAM2602 and Aurkin A, which disrupt the complex to induce spindle defects and inhibit tumor growth with potentially higher selectivity than traditional ATP-competitive inhibitors [1, 2, 7].

Other names

AURKA-TPX2 complexAurora A-TPX2 interactionAurora A-TPX2 holoenzymeSTK15-TPX2 complexTargeting protein for Xklp2-Aurora kinase A complex

Disruption of the protein-protein interaction (PPI) between Aurora kinase A and TPX2, which prevents the allosteric activation of the kinase, its localization to the mitotic spindle, and its protection from dephosphorylation and proteasomal degradation [1, 3, 10].