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An engineered minimal chromosomal passenger complex reveals a role for INCENP/Sli15 spindle association in chromosome biorientation
The four-subunit chromosomal passenger complex (CPC), whose enzymatic subunit is Aurora B kinase, promotes chromosome biorientation by detaching incorrect kinetochore–microtubule attachments. In this study, we use a combination of truncations and artificial dimerization in budding yeast to define th...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5379952/ https://www.ncbi.nlm.nih.gov/pubmed/28314741 http://dx.doi.org/10.1083/jcb.201609123 |
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author | Fink, Sarah Turnbull, Kira Desai, Arshad Campbell, Christopher S. |
author_facet | Fink, Sarah Turnbull, Kira Desai, Arshad Campbell, Christopher S. |
author_sort | Fink, Sarah |
collection | PubMed |
description | The four-subunit chromosomal passenger complex (CPC), whose enzymatic subunit is Aurora B kinase, promotes chromosome biorientation by detaching incorrect kinetochore–microtubule attachments. In this study, we use a combination of truncations and artificial dimerization in budding yeast to define the minimal CPC elements essential for its biorientation function. We engineered a minimal CPC comprised of the dimerized last third of the kinase-activating Sli15/INCENP scaffold and the catalytic subunit Ipl1/Aurora B. Although native Sli15 is not oligomeric, artificial dimerization suppressed the biorientation defect and lethality associated with deletion of a majority of its microtubule-binding domain. Dimerization did not act through a physical clustering-based kinase activation mechanism but instead promoted spindle association, likely via a putative helical domain in Sli15 that is essential even when dimerized and is required to target kinetochore substrates. Based on the engineering and characterization of a minimal CPC, we suggest that spindle association is important for active Ipl1/Aurora B complexes to preferentially destabilize misattached kinetochores. |
format | Online Article Text |
id | pubmed-5379952 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-53799522017-10-03 An engineered minimal chromosomal passenger complex reveals a role for INCENP/Sli15 spindle association in chromosome biorientation Fink, Sarah Turnbull, Kira Desai, Arshad Campbell, Christopher S. J Cell Biol Research Articles The four-subunit chromosomal passenger complex (CPC), whose enzymatic subunit is Aurora B kinase, promotes chromosome biorientation by detaching incorrect kinetochore–microtubule attachments. In this study, we use a combination of truncations and artificial dimerization in budding yeast to define the minimal CPC elements essential for its biorientation function. We engineered a minimal CPC comprised of the dimerized last third of the kinase-activating Sli15/INCENP scaffold and the catalytic subunit Ipl1/Aurora B. Although native Sli15 is not oligomeric, artificial dimerization suppressed the biorientation defect and lethality associated with deletion of a majority of its microtubule-binding domain. Dimerization did not act through a physical clustering-based kinase activation mechanism but instead promoted spindle association, likely via a putative helical domain in Sli15 that is essential even when dimerized and is required to target kinetochore substrates. Based on the engineering and characterization of a minimal CPC, we suggest that spindle association is important for active Ipl1/Aurora B complexes to preferentially destabilize misattached kinetochores. The Rockefeller University Press 2017-04-03 /pmc/articles/PMC5379952/ /pubmed/28314741 http://dx.doi.org/10.1083/jcb.201609123 Text en © 2017 Fink et al. http://www.rupress.org/terms/https://creativecommons.org/licenses/by-nc-sa/4.0/This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Research Articles Fink, Sarah Turnbull, Kira Desai, Arshad Campbell, Christopher S. An engineered minimal chromosomal passenger complex reveals a role for INCENP/Sli15 spindle association in chromosome biorientation |
title | An engineered minimal chromosomal passenger complex reveals a role for INCENP/Sli15 spindle association in chromosome biorientation |
title_full | An engineered minimal chromosomal passenger complex reveals a role for INCENP/Sli15 spindle association in chromosome biorientation |
title_fullStr | An engineered minimal chromosomal passenger complex reveals a role for INCENP/Sli15 spindle association in chromosome biorientation |
title_full_unstemmed | An engineered minimal chromosomal passenger complex reveals a role for INCENP/Sli15 spindle association in chromosome biorientation |
title_short | An engineered minimal chromosomal passenger complex reveals a role for INCENP/Sli15 spindle association in chromosome biorientation |
title_sort | engineered minimal chromosomal passenger complex reveals a role for incenp/sli15 spindle association in chromosome biorientation |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5379952/ https://www.ncbi.nlm.nih.gov/pubmed/28314741 http://dx.doi.org/10.1083/jcb.201609123 |
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