Linking kinetochore attachment to checkpoint control: the role of Aurora B in BubR1 acetylation.

We report that Aurora B kinase-mediated phosphorylation is essential for BubR1 acetylation at lysine 250 (K250), a modification required to preserve the mitotic checkpoint complex (MCC) and ensure accurate chromosome segregation. This Aurora B-BubR1 acetylation axis provides a mechanistic explanation for how kinetochore-microtubule attachment status is transduced to spindle assembly checkpoint (SAC) activity. Aurora B phosphorylates BubR1 at Serine 39 (and Ser16) in response to unattachment, and this phosphorylation is indispensable for subsequent K250 acetylation. Using a monoclonal anti-AcK250 antibody in structured illumination microscopy, we demonstrate that BubR1 acetylation sustains the fibrous corona, as shown by the crescent-shaped expansion of ZW10 and MAD2 surrounding kinetochores. Loss of either CENP-E or BubR1 acetylation abolishes fibrous corona, indicating that the interaction between acetylated BubR1 and CENP-E connects lateral attachment with the prevention of premature corona disassembly until proper end-on attachment is achieved. Disruption of Aurora B-mediated phosphorylation compromises K250 acetylation, fibrous corona maintenance, and MCC stability, whereas expression of a K250 acetylation-mimetic BubR1 rescues these defects in S16A/S39A phosphorylation-deficient mutants. Together, our findings establish a phosphorylation-acetylation cascade in BubR1 as a critical SAC signaling pathway and identify this axis as a promising therapeutic target in cancers driven by chromosomal instability.