Aurora kinase B-Inner centromere protein complex (Aurora B-INCENP)

Aurora kinase B (Aurora B) is a vital serine/threonine kinase that acts as the catalytic core of the Chromosomal Passenger Complex (CPC). Its function is intrinsically linked to the Inner Centromere Protein (INCENP), which serves as a scaffold and an essential allosteric activator; binding of the INCENP IN-box to Aurora B induces the active conformation of the kinase's T-loop [1, 2]. This complex is a master regulator of mitosis, ensuring accurate chromosome condensation, proper kinetochore-microtubule attachments, and the successful completion of cytokinesis [7, 12]. In many cancers, the Aurora B-INCENP complex is overexpressed, contributing to chromosomal instability, aneuploidy, and aggressive tumor progression [9, 10, 13]. As a result, it is a high-priority therapeutic target, with several small-molecule inhibitors designed to compete for the ATP-binding site of Aurora B, thereby inducing mitotic catastrophe and apoptosis in rapidly dividing cells [3, 10]. However, the clinical development of these inhibitors has been hampered by significant safety concerns, particularly dose-limiting neutropenia and the potential for off-target effects on normal cell division [10].

Other names

AURKB-INCENP complexChromosomal passenger complex (catalytic core)STK12-INCENPAurora kinase B-INCENP complex

ATP-competitive inhibition of the Aurora kinase B catalytic subunit within the Aurora B-INCENP complex, which prevents the phosphorylation of key mitotic substrates such as Histone H3 and MCAK, thereby disrupting chromosome alignment, spindle assembly checkpoint signaling, and cytokinesis [2, 10].