- Aurora A kinase is a serine/threonine kinase that plays a central role in early mitotic events, particularly centrosome maturation, spindle assembly and chromosome alignment. Unlike Aurora B, which operates at centromeres and the spindle midzone as part of the Chromosomal Passenger Complex, Aurora A functions primarily at centrosomes and spindle poles. Its activity ensures that the mitotic spindle forms correctly and that chromosomes are positioned accurately before segregation. Because spindle architecture determines the fidelity of chromosome segregation, Aurora A is indispensable for maintaining genomic stability.
- Aurora A localises to centrosomes during late G2 and early mitosis, where it promotes centrosome maturation. This process involves the recruitment of pericentriolar material, expansion of microtubule‑nucleating capacity and activation of proteins such as TACC3, TPX2 and NEDD1. Aurora A phosphorylates several of these substrates, enhancing microtubule stability and organisation. Through TPX2 binding, Aurora A becomes activated and protected from degradation, forming a regulatory module that drives spindle formation. TPX2 not only activates Aurora A but also targets it to spindle microtubules, ensuring that Aurora A’s activity is spatially restricted to regions where spindle assembly is taking place.
- During prometaphase, Aurora A contributes to the establishment of a bipolar spindle by regulating microtubule dynamics and centrosome separation. It phosphorylates kinesin motor proteins, including Eg5, which generate outward forces that push centrosomes apart. Proper centrosome separation is essential for forming a bipolar spindle capable of capturing kinetochores efficiently. Aurora A also stabilises kinetochore‑associated microtubules, indirectly supporting chromosome congression to the metaphase plate. Although Aurora A does not directly participate in mitotic error correction, its role in spindle geometry ensures that kinetochores encounter microtubules in orientations conducive to correct bi‑orientation.
- Aurora A’s functions extend beyond spindle assembly. It contributes to mitotic entry by activating PLK1 and regulating cyclin B–Cdk1 localisation. It also participates in asymmetric cell division, particularly in stem cells, where Aurora A helps establish polarity cues. These non‑canonical roles highlight Aurora A’s importance in both proliferative and developmental contexts.
- Dysregulation of Aurora A is strongly associated with cancer. Aurora A is frequently amplified or overexpressed in colorectal, breast, ovarian, pancreatic and haematological malignancies. Overexpression leads to centrosome amplification, multipolar spindle formation and chromosomal instability (CIN), all of which promote tumour evolution. Aurora A also phosphorylates and stabilises oncogenic proteins such as MYC and N‑MYC, further contributing to malignant transformation. Because of these roles, Aurora A is a major therapeutic target. Several Aurora A inhibitors, including alisertib (MLN8237), have entered clinical trials and show promise in treating cancers characterised by high Aurora A activity.
- In summary, Aurora A kinase is the master regulator of centrosome maturation, spindle assembly and chromosome alignment. By controlling microtubule dynamics, centrosome separation and early mitotic progression, Aurora A ensures that the spindle apparatus forms correctly and that chromosomes are positioned for accurate segregation. Its dysregulation drives chromosomal instability and tumour progression, making Aurora A a key focus of mitotic research and cancer therapy development.
