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Polo-like kinase 4 kinase activity limits centrosome overduplication by autoregulating its own stability
Accurate control of the number of centrosomes, the major microtubule-organizing centers of animal cells, is critical for the maintenance of genome integrity. Abnormalities in centrosome number can promote errors in spindle formation that lead to subsequent chromosome missegregation, and extra centro...
Autores principales: | , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2010
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2813471/ https://www.ncbi.nlm.nih.gov/pubmed/20100909 http://dx.doi.org/10.1083/jcb.200911102 |
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author | Holland, Andrew J. Lan, Weijie Niessen, Sherry Hoover, Heather Cleveland, Don W. |
author_facet | Holland, Andrew J. Lan, Weijie Niessen, Sherry Hoover, Heather Cleveland, Don W. |
author_sort | Holland, Andrew J. |
collection | PubMed |
description | Accurate control of the number of centrosomes, the major microtubule-organizing centers of animal cells, is critical for the maintenance of genome integrity. Abnormalities in centrosome number can promote errors in spindle formation that lead to subsequent chromosome missegregation, and extra centrosomes are found in many cancers. Centrosomes are comprised of a pair of centrioles surrounded by amorphous pericentriolar material, and centrosome duplication is controlled by centriole replication. Polo-like kinase 4 (Plk4) plays a key role in initiating centriole duplication, and overexpression of Plk4 promotes centriole overduplication and the formation of extra centrosomes. Using chemical genetics, we show that kinase-active Plk4 is inherently unstable and targeted for degradation. Plk4 is shown to multiply self-phosphorylate within a 24–amino acid phosphodegron. Phosphorylation of multiple sites is required for Plk4 instability, indicating a requirement for a threshold level of Plk4 kinase activity to promote its own destruction. We propose that kinase-mediated, autoregulated instability of Plk4 self-limits Plk4 activity so as to prevent centrosome amplification. |
format | Text |
id | pubmed-2813471 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-28134712010-07-25 Polo-like kinase 4 kinase activity limits centrosome overduplication by autoregulating its own stability Holland, Andrew J. Lan, Weijie Niessen, Sherry Hoover, Heather Cleveland, Don W. J Cell Biol Research Articles Accurate control of the number of centrosomes, the major microtubule-organizing centers of animal cells, is critical for the maintenance of genome integrity. Abnormalities in centrosome number can promote errors in spindle formation that lead to subsequent chromosome missegregation, and extra centrosomes are found in many cancers. Centrosomes are comprised of a pair of centrioles surrounded by amorphous pericentriolar material, and centrosome duplication is controlled by centriole replication. Polo-like kinase 4 (Plk4) plays a key role in initiating centriole duplication, and overexpression of Plk4 promotes centriole overduplication and the formation of extra centrosomes. Using chemical genetics, we show that kinase-active Plk4 is inherently unstable and targeted for degradation. Plk4 is shown to multiply self-phosphorylate within a 24–amino acid phosphodegron. Phosphorylation of multiple sites is required for Plk4 instability, indicating a requirement for a threshold level of Plk4 kinase activity to promote its own destruction. We propose that kinase-mediated, autoregulated instability of Plk4 self-limits Plk4 activity so as to prevent centrosome amplification. The Rockefeller University Press 2010-01-25 /pmc/articles/PMC2813471/ /pubmed/20100909 http://dx.doi.org/10.1083/jcb.200911102 Text en © 2010 Holland et al. 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.jcb.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/). |
spellingShingle | Research Articles Holland, Andrew J. Lan, Weijie Niessen, Sherry Hoover, Heather Cleveland, Don W. Polo-like kinase 4 kinase activity limits centrosome overduplication by autoregulating its own stability |
title | Polo-like kinase 4 kinase activity limits centrosome overduplication by autoregulating its own stability |
title_full | Polo-like kinase 4 kinase activity limits centrosome overduplication by autoregulating its own stability |
title_fullStr | Polo-like kinase 4 kinase activity limits centrosome overduplication by autoregulating its own stability |
title_full_unstemmed | Polo-like kinase 4 kinase activity limits centrosome overduplication by autoregulating its own stability |
title_short | Polo-like kinase 4 kinase activity limits centrosome overduplication by autoregulating its own stability |
title_sort | polo-like kinase 4 kinase activity limits centrosome overduplication by autoregulating its own stability |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2813471/ https://www.ncbi.nlm.nih.gov/pubmed/20100909 http://dx.doi.org/10.1083/jcb.200911102 |
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