Fig. 9
Summary model: spatial and temporal control of CENP-F by importin beta and MTs. Upper panel: in a normal mitosis, importin beta interacts with CENP-F along the spindle microtubules (MTs) and contributes to regulate the balance between pole- and kinetochore (KT)-associated CENP-F during spindle organisation (metaphase panel). In anaphase, when MTs reorganise in the central spindle and importin beta begins to relocalise at sites where the nuclear envelope (NE) will reform, CENP-F becomes accessible to the ubiquitin/proteasome system (rightmost panel, zoom) via recognition of the KEN box by APC/Ccdc20/cdh123. Bottom panel: importin beta overexpression disrupts the spatial control of CENP-F in metaphase, accumulating it at poles, and also causes its persistence in late mitosis. In anaphase, overexpressed importin beta molecules, in addition to localising at the reforming NE, continue in part to interact with CENP-F via the NLS, possibly hindering the recognition of the adjacent KEN box (rightmost panel, zoom) and inhibiting subsequent degradation. Importin beta may also stabilise CENP-F by displacing it at poles, away from sites where the APC/Ccdc20/cdh1 is active. Functional MTs provide physical tracks for importin beta and CENP-F interactions, and inhibiting their polymerisation or dynamics reverses the stabilising effect of importin beta (Created in BioRender).
