Aurora B KinaseEdit
Aurora B kinase is a central regulator of cell division in eukaryotes, acting as the catalytic core of a multi-protein complex that choreographs chromosome behavior from condensation through cytokinesis. In humans, it belongs to the Aurora kinase family and is encoded by the AURKB gene. The protein is best known for its role within the Chromosomal Passenger Complex, which also includes INCENP, Survivin (encoded by BIRC5), and Borealin (CDCA8). The CPC relocates within the cell as mitosis progresses, first concentrating at centromeres to monitor kinetochore–microtubule attachments, and later moving to the central spindle and midbody to coordinate the final stages of cell division. Through targeted phosphorylation of a broad set of substrates, Aurora B ensures accurate chromosome alignment, segregation, and successful abscission, while helping to prevent two daughter cells from inheriting unequal or damaged genetic material.
Aurora B functions as a key part of a surveillance-and-action system that couples mechanical cues at the kinetochore with biochemical responses. Its activity is tightly regulated by the assembly state of the CPC and by phosphorylation events that modulate its kinase activity. As chromosomes align, Aurora B phosphorylates substrates at centromeres to destabilize improper microtubule attachments, allowing correction before anaphase. Once correct attachments are established and tension across sister chromatids is achieved, the CPC’s activity is spatially constrained, enabling stable chromosome segregation. Additional roles extend into cytokinesis, where Aurora B helps orchestrate the ingression of the cleavage furrow and ensures that division proceeds only after chromosomes are properly partitioned.
From a molecular standpoint, Aurora B phosphorylates a variety of substrates that influence chromosome structure, kinetochore function, and microtubule dynamics. Notable targets include histone H3 on Ser10 (H3S10), a modification associated with chromosome condensation and mitotic progression, and components of the kinetochore–microtubule interface such as the NDC80 complex. The kinase also modulates microtubule depolymerization in the vicinity of centromeres via factors like MCAK, and it participates in regulating the spindle assembly checkpoint to prevent premature progression into anaphase. The CPC’s localization is coordinated by interactions among its components and by post-translational modifications of chromatin, including histone marks that recruit the complex to centromeric regions.
Clinical relevance and research into Aurora B have grown from a basic-science focus to an exploration of targeted cancer therapies. Overexpression or dysregulated activity of AURKB has been observed in various cancers, linking the kinase to tumorigenesis through promotion of chromosomal instability (CIN) and abnormal mitosis. This has spurred interest in small-molecule inhibitors that selectively dampen Aurora B activity. Several inhibitors have entered preclinical and clinical evaluation, including Barasertib (AZD1152), a relatively selective Aurora B inhibitor, and other broad-spectrum ATP-competitive compounds such as Tozasertib (VX-680) and Danusertib. These agents have demonstrated anti-tumor activity in some models, particularly when used in combination with DNA-damaging therapies or microtubule-targeting agents. However, their clinical application faces challenges common to mitotic kinase inhibitors: toxicity to normal proliferating tissues, a narrow therapeutic window, and the emergence of resistance mechanisms. Ongoing work seeks to identify predictive biomarkers of sensitivity, optimize dosing regimens, and define the patient populations most likely to benefit. For example, p53 status, baseline CIN, and the specific cancer context can influence responsiveness to Aurora B–targeted strategies. Related inhibitors and research tools also probe the broader roles of the CPC and its isoforms in mitosis and meiosis across different organisms, including yeast Ipl1 and higher eukaryotes.
Controversies and debates around Aurora B research and therapeutics center on several scientific and clinical issues. The essential nature of Aurora B for accurate chromosome segregation raises questions about the therapeutic window for inhibitors: because normal dividing cells share the same fundamental mitotic machinery as cancer cells, systemic inhibition risks substantial collateral damage to healthy tissues such as bone marrow and epithelia. This has driven emphasis on isoform selectivity, dosing strategies, and combination therapies designed to maximize tumor effects while minimizing toxicity. There is also ongoing discussion about the degree to which cancer cells rely on Aurora B activity versus compensatory pathways, such as related kinases in the CPC or parallel mitotic regulators, which can influence resistance development. The specificity of inhibitors remains a practical concern; many compounds inhibit multiple aurora kinases to varying extents, complicating interpretation of results and the design of targeted regimens. Finally, while CIN is a hallmark of many cancers and a potential vulnerability, there is debate about whether further increasing CIN through Aurora B inhibition always yields therapeutic benefit or if it can instead promote adaptive tumor evolution in some contexts.
In the broader landscape of cell biology and cancer therapy, Aurora B sits at the intersection of fundamental mitosis research and translational science. Its study informs understanding of how cells monitor chromosome-microtubule attachments, how chromatin modifications coordinate division, and how disrupting these processes can be leveraged against cancer. The ongoing exploration of Aurora B biology continues to refine the comprehension of mitotic checkpoints, kinetochore function, and the precise choreography of the CPC during each stage of cell division.