Plk1-dependent cell cycle-independent furrowing triggered by phosphomimetic mutations of the INCENP STD motif

Abstract

Timely and precise control of Aurora B kinase, the chromosomal passenger complex (CPC) catalytic subunit, is essential for accurate chromosome segregation and cytokinesis. Post-translational modifications of the CPC subunits are directly involved in controlling Aurora B activity. We have identified a highly conserved acidic STD-rich motif of INCENP phosphorylated during mitosis in vivo and by Plk1 in vitro that is involved in controlling Aurora B activity. Using an INCENP conditional-knockout cell line, we show that impairing phosphorylation status of this region disrupts chromosome congression and induces cytokinesis failure. In contrast, mimicking constitutive phosphorylation not only rescues cytokinesis but also induces ectopic furrows and contractile ring formation in a Plk1- and ROCK1- dependent manner independent of cell cycle and microtubule status. Our experiments identify the INCENP STD motif as a novel switch whose phospho-regulation is key for chromosome alignment and cytokinesis.