- Aurora B is a serine/threonine kinase and the catalytic core of the Chromosomal Passenger Complex (CPC), functioning together with INCENP, Borealin and Survivin. As the master regulator of chromosome segregation, tension sensing and cytokinesis, Aurora B ensures that mitosis proceeds with high fidelity. Its dynamic localisation—from chromosome arms to centromeres, then to the spindle midzone and midbody—allows it to supervise each stage of cell division.
- Aurora B’s activation depends on INCENP. The IN‑box domain of INCENP binds Aurora B, stabilising the kinase and promoting autophosphorylation of its activation loop. This creates a positive feedback loop: Aurora B phosphorylates INCENP, which further enhances Aurora B activity. Survivin and Borealin position the CPC at centromeres, enabling Aurora B to monitor kinetochore–microtubule attachments.
- Aurora B’s most critical role is error correction. During prometaphase and metaphase, Aurora B phosphorylates kinetochore substrates such as Ndc80, KNL1 and MCAK. These phosphorylation events destabilise incorrect microtubule attachments—syntelic, monotelic or merotelic—allowing the cell to re‑establish proper bi‑orientation. This tension‑sensing mechanism prevents chromosome mis‑segregation and aneuploidy.
- Aurora B also regulates the spindle assembly checkpoint (SAC). When kinetochores lack tension or proper attachment, Aurora B maintains SAC signalling, preventing premature anaphase onset. Once all chromosomes achieve bi‑orientation, Aurora B activity at centromeres decreases, allowing SAC silencing and progression to anaphase.
- During anaphase, Aurora B relocates to the central spindle. This relocation is essential for regulating spindle midzone formation, microtubule bundling and chromatid separation. INCENP’s long coiled‑coil domain facilitates this movement by interacting with microtubules and motor proteins.
- In cytokinesis, Aurora B accumulates at the midbody, where it phosphorylates proteins involved in contractile ring formation, membrane abscission and midbody stability. Disruption of Aurora B at this stage leads to cytokinesis failure, resulting in binucleated or polyploid cells.
- Aurora B is frequently overexpressed in cancer. Tumour cells exploit Aurora B to tolerate mitotic errors, maintain chromosomal instability and resist apoptosis. High Aurora B expression correlates with poor prognosis in colorectal, breast, lung and haematological malignancies. Several Aurora B inhibitors—including barasertib (AZD1152)—are under clinical investigation as anti‑mitotic cancer therapies.
- In summary, Aurora B is the catalytic engine of the CPC and a master regulator of mitotic fidelity. By correcting kinetochore–microtubule attachment errors, maintaining the spindle assembly checkpoint and coordinating cytokinesis, Aurora B preserves genomic stability. Its dysregulation in cancer makes it a major therapeutic target.
