Aurora A-TPX2 protein–protein interface

The **Aurora A-TPX2 protein-protein interface** refers to the direct interaction site between Aurora kinase A, a serine/threonine kinase essential for mitosis, and TPX2 (Targeting Protein for XKLP2), a microtubule-associated protein. TPX2 binds to Aurora A via two short motifs within its N-terminal 43 amino acids, stabilizing the kinase in its active conformation, protecting it from dephosphorylation, and targeting it to mitotic spindle microtubules[1][3][5]. The Aurora A–TPX2 complex is essential for spindle assembly, chromosome segregation, and mitotic progression. Both proteins are frequently co-overexpressed in various tumors, making their interaction an attractive and increasingly validated anti-cancer target. Unlike ATP-competitive Aurora kinase inhibitors, which often lack selectivity, disruption of this interface with small molecules or peptides offers a route to achieve highly specific inhibition of Aurora A function with the potential to destabilize the kinase and lower its overall levels[2][4][8]. Interference at this interface impacts biomarkers such as phospho-Thr288 and phospho-histone H3, which are indicative of mitotic kinase activity and anti-tumor efficacy[4][8]. Novel PPI inhibitors, such as CAM2602, have demonstrated in vivo efficacy and promising biomarker modulation in preclinical tumor models, suggesting clinical potential for this therapeutic strategy[4][8].

Other names

Aurora-A–TPX2 interfaceAurora kinase A–TPX2 interactionAurora A/TPX2 complex

Disruption of the Aurora A–TPX2 interaction impairs Aurora A activation, localization, and stability, leading to dysfunction in mitotic spindle assembly; this represents a promising approach for anti-cancer therapy[2][4]. PPI inhibitors prevent TPX2-mediated Aurora A activation and protect Thr288 from dephosphorylation, resulting in loss of Aurora A function[1][2][4][8].