Abstract
The Aurora B chromosomal passenger complex (CPC) is a conserved regulator of mitosis. Its functions require localization first to the chromosome arms and then centromeres in mitosis and subsequently the central spindle in anaphase. Here, we analyze the requirements for core CPC subunits, survivin and INCENP, and the mitotic kinesin-like protein 2 (MKLP2) in targeting to these distinct localizations. Centromere recruitment of the CPC requires interaction of survivin with histone H3 phosphorylated at threonine 3, and we provide a complete structure of this assembly. Furthermore, we show that the INCENP RRKKRR-motif is required for both centromeric localization of the CPC in metaphase and MKLP2-dependent transport in anaphase. MKLP2 and DNA bind competitively to this motif, and INCENP T59 phosphorylation acts as a switch preventing MKLP2 binding in metaphase. In anaphase, CPC binding promotes the microtubule-dependent ATPase activity of MKLP2. These results explain how centromere targeting of the CPC in mitosis is coupled to its movement to the central spindle in anaphase.
Highlights
Aurora B is a crucial mitotic kinase that regulates chromosome condensation in prophase, microtubule attachment to kinetochores during prometaphase and metaphase, and anaphase spindle microtubule dynamics and cytokinesis (Carmena et al, 2012)
chromosomal passenger complex (CPC) targeting to centromeres and the central spindle requires the first 80 amino acids of INCENP The CPC makes multiple contacts with chromatin, and mitotic kinesin-like protein 2 (MKLP2) may compete for one or more of the interactions with phosphorylated histone H3 or nucleosomes
Moving toward a more complete understanding of CPC dynamics MKLP2 actively promotes the movement of the CPC from chromatin to the central spindle at the onset of anaphase
Summary
Aurora B is a crucial mitotic kinase that regulates chromosome condensation in prophase, microtubule attachment to kinetochores during prometaphase and metaphase, and anaphase spindle microtubule dynamics and cytokinesis (Carmena et al, 2012). These functions require localization to specific sites on chromosome arms, centromeres, and microtubules (Hindriksen et al, 2017). Aurora B localization and activation throughout mitosis and cytokinesis depend on three other proteins: INCENP, survivin, and borealin (Adams et al, 2000; 2001; Gassmann et al, 2004; Romano et al, 2003; Sampath et al, 2004; Vader et al, 2006; Wheatley et al, 2001) Together, these proteins form the tetrameric chromosomal passenger complex (CPC).
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