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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...

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Detalles Bibliográficos
Autores principales: Holland, Andrew J., Lan, Weijie, Niessen, Sherry, Hoover, Heather, Cleveland, Don W.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2010
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.
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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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