Inner centromere protein (INCENP)

Inner centromere protein (INCENP) is a core scaffolding and regulatory protein of the chromosome passenger complex (CPC), which orchestrates crucial mitotic events including chromosome alignment, spindle assembly checkpoint control, and cytokinesis. INCENP functions by recruiting and activating Aurora B kinase through its conserved C-terminal IN box, forming a flexible linker between the centromere localization module and the kinase activation domain. The N-terminal region forms a three-helix bundle with Survivin and Borealin, anchoring CPC to the inner centromere, while the central region acts as a highly extensible single α-helix, allowing dynamic positioning of Aurora B for substrate phosphorylation. INCENP is essential for proper chromosome segregation, phosphorylation of histone H3, and cell division; its depletion or defective function leads to mitotic errors, cytokinesis failure, polyploidy, and developmental abnormalities. INCENP is under investigation as a mitotic machinery target in cancer therapy, primarily via drugs that target Aurora B kinase, though direct INCENP inhibitors remain experimental.

Other names

IncenpInner centromere protein INCENPChromosomal passenger proteinInner centromere protein antigens 135/155kDaFLJ31633Binds and activates Aurora-B and -CChromosomal passenger complex subunit INCENP

Inhibition of Aurora B kinase (disrupts INCENP-Aurora B interaction, blocks chromosome segregation and cytokinesis); Disruption of CPC assembly or function (potential future strategies); Indirect disruption of centromere/kinetochore function.