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Mol Biol Cell 2017 Jun 01;2811:1444-1456. doi: 10.1091/mbc.E16-12-0860.
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Chromosomal passenger complex hydrodynamics suggests chaperoning of the inactive state by nucleoplasmin/nucleophosmin.

Hanley ML , Yoo TY , Sonnett M , Needleman DJ , Mitchison TJ .

The chromosomal passenger complex (CPC) is a conserved, essential regulator of cell division. As such, significant anti-cancer drug development efforts have been focused on targeting it, most notably by inhibiting its AURKB kinase subunit. The CPC is activated by AURKB-catalyzed autophosphorylation on multiple subunits, but how this regulates CPC interactions with other mitotic proteins remains unclear. We investigated the hydrodynamic behavior of the CPC in Xenopus laevis egg cytosol using sucrose gradient sedimentation and in HeLa cells using fluorescence correlation spectroscopy. We found that autophosphorylation of the CPC decreases its sedimentation coefficient in egg cytosol and increases its diffusion coefficient in live cells, indicating a decrease in mass. Using immunoprecipitation coupled with mass spectrometry and immunoblots, we discovered that inactive, unphosphorylated CPC interacts with nucleophosmin/nucleoplasmin proteins, which are known to oligomerize into pentamers and decamers. Autophosphorylation of the CPC causes it to dissociate from nucleophosmin/nucleoplasmin. We propose that nucleophosmin/nucleoplasmin complexes serve as chaperones that negatively regulate the CPC and/or stabilize its inactive form, preventing CPC autophosphorylation and recruitment to chromatin and microtubules in mitosis.

PubMed ID: 28404751
PMC ID: PMC5449145
Article link: Mol Biol Cell
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: aurka aurkb birc5 cdca8 cdca9 cdk1 h2ac21 incenp isyna1 npm1 npm2 pard3 psmd6 stmn1
Antibodies: Acta1 Ab7 Incenp Ab2 Tuba4b Ab3 aurka/b Ab1 birc5 Ab1 cdca9 Ab1 h2afz Ab1 mpm2 Ab1

Article Images: [+] show captions
References [+] :
Adams, INCENP binds the Aurora-related kinase AIRK2 and is required to target it to chromosomes, the central spindle and cleavage furrow. 2000, Pubmed, Xenbase