The chromosomal passenger complex (CPC): from easy rider to the godfather of mitosis

Abstract

The chromosomal passenger complex (CPC) is a 'master controller' of cell division that is formed by a kinase module (Aurora B kinase) and a localization module (the scaffolding protein inner centromere protein (INCENP), survivin and borealin). Multiple post-translational modifications of CPC components contribute to the appropriate localization and regulation of Aurora B activity. Full activation of Aurora B kinase is a complex multistage process that is mediated by the other CPC components and other cell cycle kinases. In early mitosis, CPC recruitment to the inner centromere is mediated by post-translational modifications of two histones: phosphorylation of histone H3 (by haspin kinase) and of histone H2A (by Bub1 kinase). The baculovirus IAP repeat (BIR) domain of survivin recognizes H3 phosphorylated at Thr3. Further enrichment of the CPC at the inner centromere is mediated by Aurora B-dependent regulatory feedback loops. Roles of the CPC in early mitosis include the regulation of chromosome structure, kinetochore–microtubule attachments and the spindle assembly checkpoint. The CPC relocalizes to central spindle microtubules at the onset of anaphase in a highly regulated process that is mediated by a decrease of cyclin-dependent kinase 1 (Cdk1) activity, interaction with the kinesin mitotic kinesin-like protein 2 (Mklp2) and under the control of several phosphatases and Aurora B kinase itself. Functions of the CPC in late mitosis include the formation and stabilization of the spindle midzone in anaphase and the regulation of the contractile ring formation. The CPC has further roles later on in cytokinesis, in which it regulates furrow ingression and the abscission checkpoint.