The proteasome promotes cytokinetic abscission by relieving an Aurora B-dependent inhibition of ESCRT-III dynamics.

Cytokinesis finalizes cell division by physically separating the daughter cells. After furrow ingression, the intercellular bridge (ICB) connecting the dividing cells is cut via microtubule severing, followed by membrane scission, which requires dynamic ESCRT-III polymers. Proteasomal degradation is crucial for mitotic exit and the early steps of cytokinesis, but whether it plays a role in abscission is unknown. Here, we found that inhibiting the proteasome after furrow ingression in human cells led to increased Aurora B levels at the ICB and delayed both microtubule cutting and membrane scission. Overexpression of Aurora B phenocopied these cytokinetic defects, whereas inhibiting Aurora B activity fully rescued the defects caused by proteasome inhibition. Mechanistically, proteasome inhibition increased the levels of active Aurora B, enhanced the phosphorylation of its substrate CHMP4C, and reduced the amount of the ESCRT-III remodeling ATPase VPS4 at the ICB. Consequently, this led to a reduction in the dynamics of the ESCRT-III polymer at the ICB. Remarkably, proteasome inhibition did not delay abscission in cells expressing a mutant of CHMP4C that cannot be phosphorylated by Aurora B, thus demonstrating that the function of the proteasome in abscission is to degrade Aurora B and thereby limit CHMP4C phosphorylation. Our findings reveal a key role of the proteasome in the final step of cell division by decreasing Aurora B levels and activity to enable ESCRT-III function in abscission.