Current Biology
Volume 23, Issue 12, 17 June 2013, Pages 1136-1143
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Aurora B Defines Its Own Chromosomal Targeting by Opposing the Recruitment of the Phosphatase Scaffold Repo-Man

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Highlights

  • Aurora B opposes the histone binding of Repo-Man by phosphorylation of S893

  • Repo-Man has distinct binding sites for PP1 and PP2A

  • PP2A promotes Repo-Man targeting to chromosomes by dephosphorylation of S893

  • PP2A-mediated Repo-Man chromosome targeting is essential to dephosphorylate H3T3ph

Summary

Aurora B is the catalytic subunit of the chromosomal passenger complex (CPC), which coordinates mitotic processes through phosphorylation of key regulatory proteins [1]. In prometaphase, the CPC is enriched at the centromeres to regulate the spindle checkpoint and kinetochore-microtubule interactions. Centromeric CPC binds to histone H3 that is phosphorylated at T3 (H3T3ph) by Aurora B-stimulated Haspin [2, 3, 4, 5]. PP1/Repo-Man acts antagonistically to Haspin and dephosphorylates H3T3ph at the chromosome arms but is somehow prevented from causing a net dephosphorylation of centromeric H3T3ph during prometaphase [6, 7]. Here, we show that Aurora B phosphorylates Repo-Man at S893, preventing its recruitment by histones. We also identify PP2A as a mitotic interactor of Repo-Man that dephosphorylates S893 and thereby promotes the targeting of Repo-Man to chromosomes and the dephosphorylation of H3T3ph by PP1. Thus, Repo-Man-associated PP1 and PP2A collaborate to oppose the chromosomal targeting of Aurora B. We propose that the reciprocal feedback regulation of Haspin and Repo-Man by Aurora B generates a robust bistable response that culminates in the centromeric targeting of the CPC during prometaphase.

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