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Plk1- and β-TrCP–dependent degradation of Bora controls mitotic progression
Through a convergence of functional genomic and proteomic studies, we identify Bora as a previously unknown cell cycle protein that interacts with the Plk1 kinase and the SCF–β-TrCP ubiquitin ligase. We show that the Bora protein peaks in G2 and is degraded by proteasomes in mitosis. Proteolysis of...
Autores principales: | , , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2008
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2287288/ https://www.ncbi.nlm.nih.gov/pubmed/18378770 http://dx.doi.org/10.1083/jcb.200712027 |
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author | Seki, Akiko Coppinger, Judith A. Du, Haining Jang, Chang-Young Yates, John R. Fang, Guowei |
author_facet | Seki, Akiko Coppinger, Judith A. Du, Haining Jang, Chang-Young Yates, John R. Fang, Guowei |
author_sort | Seki, Akiko |
collection | PubMed |
description | Through a convergence of functional genomic and proteomic studies, we identify Bora as a previously unknown cell cycle protein that interacts with the Plk1 kinase and the SCF–β-TrCP ubiquitin ligase. We show that the Bora protein peaks in G2 and is degraded by proteasomes in mitosis. Proteolysis of Bora requires the Plk1 kinase activity and is mediated by SCF–β-TrCP. Plk1 phosphorylates a conserved DSGxxT degron in Bora and promotes its interaction with β-TrCP. Mutations in this degron stabilize Bora. Expression of a nondegradable Bora variant prolongs the metaphase and delays anaphase onset, indicating a physiological requirement of Bora degradation. Interestingly, the activity of Bora is also required for normal mitotic progression, as knockdown of Bora activates the spindle checkpoint and delays sister chromatid segregation. Mechanistically, Bora regulates spindle stability and microtubule polymerization and promotes tension across sister kinetochores during mitosis. We conclude that tight regulation of the Bora protein by its synthesis and degradation is critical for cell cycle progression. |
format | Text |
id | pubmed-2287288 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2008 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-22872882008-10-07 Plk1- and β-TrCP–dependent degradation of Bora controls mitotic progression Seki, Akiko Coppinger, Judith A. Du, Haining Jang, Chang-Young Yates, John R. Fang, Guowei J Cell Biol Research Articles Through a convergence of functional genomic and proteomic studies, we identify Bora as a previously unknown cell cycle protein that interacts with the Plk1 kinase and the SCF–β-TrCP ubiquitin ligase. We show that the Bora protein peaks in G2 and is degraded by proteasomes in mitosis. Proteolysis of Bora requires the Plk1 kinase activity and is mediated by SCF–β-TrCP. Plk1 phosphorylates a conserved DSGxxT degron in Bora and promotes its interaction with β-TrCP. Mutations in this degron stabilize Bora. Expression of a nondegradable Bora variant prolongs the metaphase and delays anaphase onset, indicating a physiological requirement of Bora degradation. Interestingly, the activity of Bora is also required for normal mitotic progression, as knockdown of Bora activates the spindle checkpoint and delays sister chromatid segregation. Mechanistically, Bora regulates spindle stability and microtubule polymerization and promotes tension across sister kinetochores during mitosis. We conclude that tight regulation of the Bora protein by its synthesis and degradation is critical for cell cycle progression. The Rockefeller University Press 2008-04-07 /pmc/articles/PMC2287288/ /pubmed/18378770 http://dx.doi.org/10.1083/jcb.200712027 Text en Copyright © 2008, The Rockefeller University Press 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 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Research Articles Seki, Akiko Coppinger, Judith A. Du, Haining Jang, Chang-Young Yates, John R. Fang, Guowei Plk1- and β-TrCP–dependent degradation of Bora controls mitotic progression |
title | Plk1- and β-TrCP–dependent degradation of Bora controls mitotic progression |
title_full | Plk1- and β-TrCP–dependent degradation of Bora controls mitotic progression |
title_fullStr | Plk1- and β-TrCP–dependent degradation of Bora controls mitotic progression |
title_full_unstemmed | Plk1- and β-TrCP–dependent degradation of Bora controls mitotic progression |
title_short | Plk1- and β-TrCP–dependent degradation of Bora controls mitotic progression |
title_sort | plk1- and β-trcp–dependent degradation of bora controls mitotic progression |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2287288/ https://www.ncbi.nlm.nih.gov/pubmed/18378770 http://dx.doi.org/10.1083/jcb.200712027 |
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