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A rapid computational approach identifies SPICE1 as an Aurora kinase substrate
Aurora kinases play a major role in mitosis by regulating diverse substrates. Defining their critical downstream targets is important in understanding Aurora kinase function. Here we have developed an unbiased computational approach to identify new Aurora kinase substrates based on phosphorylation s...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6589576/ https://www.ncbi.nlm.nih.gov/pubmed/30485161 http://dx.doi.org/10.1091/mbc.E18-08-0495 |
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author | Deretic, Jovana Kerr, Alastair Welburn, Julie P. I. |
author_facet | Deretic, Jovana Kerr, Alastair Welburn, Julie P. I. |
author_sort | Deretic, Jovana |
collection | PubMed |
description | Aurora kinases play a major role in mitosis by regulating diverse substrates. Defining their critical downstream targets is important in understanding 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, tubulin tyrosine ligase-like polyglutamylase residues 330–624 and spindle and centriole associated protein 1, residues 549–855 (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 nonphosphorylatable 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. |
format | Online Article Text |
id | pubmed-6589576 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-65895762019-06-28 A rapid computational approach identifies SPICE1 as an Aurora kinase substrate Deretic, Jovana Kerr, Alastair Welburn, Julie P. I. Mol Biol Cell Brief Reports Aurora kinases play a major role in mitosis by regulating diverse substrates. Defining their critical downstream targets is important in understanding 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, tubulin tyrosine ligase-like polyglutamylase residues 330–624 and spindle and centriole associated protein 1, residues 549–855 (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 nonphosphorylatable 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. The American Society for Cell Biology 2019-02-01 /pmc/articles/PMC6589576/ /pubmed/30485161 http://dx.doi.org/10.1091/mbc.E18-08-0495 Text en © 2019 Deretic et al. “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology. http://creativecommons.org/licenses/by-nc-sa/3.0 This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License. |
spellingShingle | Brief Reports Deretic, Jovana Kerr, Alastair Welburn, Julie P. I. A rapid computational approach identifies SPICE1 as an Aurora kinase substrate |
title | A rapid computational approach identifies SPICE1 as an Aurora kinase substrate |
title_full | A rapid computational approach identifies SPICE1 as an Aurora kinase substrate |
title_fullStr | A rapid computational approach identifies SPICE1 as an Aurora kinase substrate |
title_full_unstemmed | A rapid computational approach identifies SPICE1 as an Aurora kinase substrate |
title_short | A rapid computational approach identifies SPICE1 as an Aurora kinase substrate |
title_sort | rapid computational approach identifies spice1 as an aurora kinase substrate |
topic | Brief Reports |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6589576/ https://www.ncbi.nlm.nih.gov/pubmed/30485161 http://dx.doi.org/10.1091/mbc.E18-08-0495 |
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