- INCENP (Inner Centromere Protein) is an essential mitotic regulator and the central scaffold of the Chromosomal Passenger Complex (CPC), which also includes Aurora B kinase, Survivin and Borealin. The CPC ensures accurate chromosome segregation, kinetochore–microtubule attachment correction and cytokinesis. INCENP’s modular architecture allows it to position Aurora B at the right place and time during mitosis, activate the kinase, and coordinate CPC relocation from centromeres to the spindle midzone and midbody.
- INCENP’s N‑terminal region forms a three‑helix bundle with Survivin and Borealin, which is essential for targeting the CPC to the inner centromere during early mitosis. This centromere localisation is independent of Aurora B activity and ensures that the CPC can monitor kinetochore–microtubule attachments.
- The C‑terminal IN‑box domain directly binds Aurora B (and Aurora C), stabilising the kinase and inducing its active conformation. This binding allosterically activates Aurora B by promoting T‑loop phosphorylation, creating a positive‑feedback loop in which Aurora B further phosphorylates INCENP to enhance its own activation.
- INCENP contains a long single‑alpha‑helix (SAH) domain that binds microtubules. This flexible “dog‑leash” spacer allows centromere‑anchored Aurora B to reach outer kinetochore substrates while maintaining CPC docking on chromatin. The SAH domain is crucial for CPC localisation and microtubule‑dependent substrate targeting.
- INCENP regulates multiple mitotic processes. At centromeres, it helps Aurora B destabilise incorrect kinetochore–microtubule attachments, promoting chromosome bi‑orientation. It also contributes to centromeric cohesion protection and spindle checkpoint maintenance. During anaphase, INCENP undergoes phosphoregulated relocation to the central spindle, enabling Aurora B to coordinate spindle midzone formation and cytokinesis.
- INCENP is highly conserved across eukaryotes. In vertebrates such as Xenopus laevis, INCENP performs similar functions, acting as a scaffold for CPC localisation, Aurora B activation and microtubule‑directed substrate targeting.
- In summary, INCENP is the structural and regulatory backbone of the CPC. Through its modular domains, INCENP positions Aurora B, activates the kinase, binds microtubules and orchestrates CPC movement across mitosis. Its functions are essential for chromosome alignment, segregation accuracy and successful cytokinesis.
