Centromere Targeting of the Chromosomal Passenger Complex Requires a Ternary Subcomplex of Borealin, Survivin, and the N-Terminal Domain of INCENP

Abstract

The chromosomal passenger complex (CPC), consisting of the serine/threonine kinase Aurora B, the inner centromere protein INCENP, Survivin, and Borealin/DasraB, has essential functions at the centromere in ensuring correct chromosome alignment and segregation. Despite observations that small interfering RNA-mediated knockdown of any one member of the CPC abolishes localization of the other subunits, it remains unclear how the complex is targeted to the centromere. We have now identified a ternary subcomplex of the CPC comprising Survivin, Borealin, and the N-terminal 58 amino acids of INCENP in vitro and in vivo. This subcomplex was found to be essential and sufficient for targeting to the centromere. Notably, Aurora B kinase, the enzymatic core of the CPC, was not required for centromere localization of the subcomplex. We demonstrate that CPC targeting to the centromere does not depend on CENP-A and hMis12, two core components for kinetochore/centromere assembly, and provide evidence that the CPC may be directed to centromeric DNA directly via the Borealin subunit. Our findings thus establish a functional module within the CPC that assembles on the N terminus of INCENP and controls centromere recruitment.

Histone deacetylase inhibitors induce mitotic slippage

“…These HDACi-induced mitotic defects are also observed with depletion of individual CPC proteins (Wheatley et al, 2001;Carvalho et al, 2003;Ditchfield et al, 2003;Hauf et al, 2003;Lens et al, 2003;Mollinari et al, 2003;Gassmann et al, 2004;Klein et al, 2006). Although HDACi treatment does not affect the levels of the CPC proteins, they fail to accumulate at the centromeres in prometaphase.…”

The Chromosomal Passenger Complex Is Required for Meiotic Acentrosomal Spindle Assembly and Chromosome Biorientation

“…of Incenp ( Figure S2) or the addition of the N-terminal tag because the N terminus contains sequences important for Incenp localization Mackay et al 1998;Klein et al 2006). In fact, myc-tagged Incenp localized throughout the spindle in 7/16 oocytes ( Figure 3G) while in 9/16 oocytes the protein was concentrated at the central spindle like wild-type Incenp ( Figure 3H).…”

Centromere localization of INCENP-Aurora B is sufficient to support spindle checkpoint function

“…In fact, Aurora B can bind to a C-terminal domain of INCENP (the so-called IN-box), which is then targeted as a to centromeres through its interaction with survivin. 12,[14][15][16][17] The stability of the CPC proteins, however, depend on the presence of all subunits, During mitosis, the chromosomal passenger complex (CpC) comprising the Aurora B kinase, INCeNp, survivin and borealin is essential for correcting non-bipolar chromosome attachments and for cytokinesis. In addition, the CpC might fullfil a role in the mitotic spindle assembly checkpoint (SAC), but this activity might be related to its role in correcting non-bipolar chromosome attachments.…”