- The Chromosomal Passenger Complex (CPC) is an essential multi‑protein complex that orchestrates the major events of mitosis, ensuring accurate chromosome segregation and successful cytokinesis. It consists of four core components: Aurora B kinase, INCENP, Borealin, and Survivin. Together, these proteins act as “passengers” that dynamically relocate to different cellular structures throughout mitosis, enabling the CPC to monitor and correct errors in chromosome alignment, spindle attachment and cell division.
- The CPC’s catalytic engine is Aurora B kinase, a serine/threonine kinase that phosphorylates multiple substrates involved in kinetochore–microtubule attachment, chromatin structure and cytokinesis. Aurora B activity is tightly regulated by its association with INCENP, which acts as a scaffold and activator. Borealin stabilises the complex and mediates interactions with chromatin, while Survivin contributes to CPC localisation and ensures proper targeting to centromeres during early mitosis.
- During prophase and prometaphase, the CPC localises to chromosome arms and then concentrates at centromeres. At this stage, Aurora B monitors kinetochore–microtubule attachments, correcting improper connections such as syntelic or merotelic attachments. This error‑correction mechanism is essential for preventing aneuploidy and maintaining genomic stability. Survivin’s BIR domain plays a key role in centromere targeting, linking CPC function to cell survival pathways.
- As cells progress to anaphase, the CPC relocates from centromeres to the central spindle. This dramatic movement—one of the defining features of the complex—allows Aurora B to regulate spindle midzone formation and ensure proper separation of sister chromatids. INCENP’s long coiled‑coil domain facilitates this relocation by interacting with microtubules and motor proteins.
- During cytokinesis, the CPC accumulates at the midbody, where it coordinates the final steps of cell division. Aurora B phosphorylates proteins involved in contractile ring formation, membrane abscission and midbody stability. Disruption of CPC function at this stage leads to cytokinesis failure, resulting in binucleated or polyploid cells.
- The CPC is also a key guardian of genomic integrity. By correcting attachment errors and regulating the spindle assembly checkpoint, it prevents chromosome mis‑segregation and mitotic catastrophe. Mutations or misregulation of CPC components—especially Aurora B and Survivin—are strongly associated with cancer. Tumour cells often overexpress Survivin and Aurora B to support rapid proliferation and resist apoptosis, making CPC components attractive therapeutic targets.
- Pharmacological inhibitors of Aurora B kinase, Survivin antagonists and CPC‑disrupting molecules are under active investigation in oncology. These therapies aim to destabilise mitosis in tumour cells, induce lethal chromosomal mis‑segregation and enhance sensitivity to chemotherapy and radiotherapy.
- In summary, the Chromosomal Passenger Complex is a dynamic, multifunctional regulator of mitosis that ensures accurate chromosome segregation and successful cytokinesis. Through coordinated actions of Aurora B, INCENP, Borealin and Survivin, the CPC maintains genomic stability and supports cell division. Its central role in cancer biology makes it a major focus of therapeutic development.
