Cormier A, Drubin DG, Barnes G

The Chromosomal Passenger Complex (CPC) is a key regulator of mitosis in eukaryotes. It is comprised of four essential and conserved proteins known in mammals/yeasts as Aurora B/Ipl1, INCENP/Sli15, Survivin/Bir1 and Borealin/Nbl1. These subunits act together in a highly controlled fashion. Regulation of Aurora B/Ipl1 kinase activity and localization are ...

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critical for CPC function. Although regulation of CPC localization and kinase activity in vivo have been investigated elsewhere, studies on the complete, 4-subunit CPC and its basic biochemical properties are only beginning. Here we describe the biochemical characterization of purified and complete S. cerevisiae 4 subunit CPC. We determined the affinity of the CPC for microtubules and demonstrated that the binding of CPC to microtubules is primarily electrostatic in nature and depends on the acidic C-terminal tail (E-hook) of tubulin. Moreover, phosphorylation of INCENP/Sli15 on its microtubule-binding (MTB) region also negatively regulates CPC affinity for microtubules. Furthermore, we show that phosphorylation of INCENP/Sli15 is required for activation of the kinase Aurora B/Ipl1 and can occur in trans. Although phosphorylation of INCENP/Sli15 is essential for activation, we determined that a version of the CPC lacking the INCENP/Sli15 MTB region (residues E91 to I631) is able to form an intact complex that retains microtubule-binding activity. Thus we conclude that this INCENP/Sli15 linker domain plays a largely regulatory function and is not essential for complex formation or microtubule binding.

Date: Jun. 27, 2013

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