A rapid computational approach identifies SPICE1 as an Aurora kinase substrate

Jovana Deretic, Alastair Kerr, Julie P I Welburn

Research output: Contribution to journalArticlepeer-review

Abstract

Aurora kinases play a major role in mitosis by regulating diverse substrates. Defining their critical downstream targets is important to understand Aurora kinase function. Here we have developed an unbiased computational approach to identify new Aurora kinase substrates based on phosphorylation site clustering, protein localization, protein structure, and species conservation. We validate the microtubule-associated proteins Clasp2, Elys, TTLL4 and SPICE1 as Aurora A and B kinases substrates in vitro. We also demonstrate that SPICE1 localization is regulated by Aurora kinases during mitosis. In the absence of Aurora kinase activity, SPICE1 remains at centrioles but does not target to the spindle. Similarly a non-phosphorylatable SPICE1 mutant no longer localizes to the spindle. Finally, we show that misregulating SPICE1 phosphorylation results in abnormal centriole number, spindle multipolarity, and chromosome alignment defects. Overall, our work indicates that temporal and spatial Aurora kinase-mediated regulation of SPICE1 is important for correct chromosome segregation. In addition, our work provides a database-search tool that enables rapid identification of Aurora kinase substrates.

Original languageEnglish
Pages (from-to)312-323
Number of pages12
JournalMolecular Biology of the Cell
Volume30
Issue number3
Early online date28 Nov 2018
DOIs
Publication statusPublished - 31 Jan 2019

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