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KAT2A/KAT2B-targeted acetylome reveals a role for PLK4 acetylation in preventing centrosome amplification
Lysine acetylation is a widespread post-translational modification regulating various biological processes. To characterize cellular functions of the human lysine acetyltransferases KAT2A (GCN5) and KAT2B (PCAF), we determined their acetylome by shotgun proteomics. One of the newly identified KAT2A/...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5095585/ https://www.ncbi.nlm.nih.gov/pubmed/27796307 http://dx.doi.org/10.1038/ncomms13227 |
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author | Fournier, Marjorie Orpinell, Meritxell Grauffel, Cédric Scheer, Elisabeth Garnier, Jean-Marie Ye, Tao Chavant, Virginie Joint, Mathilde Esashi, Fumiko Dejaegere, Annick Gönczy, Pierre Tora, László |
author_facet | Fournier, Marjorie Orpinell, Meritxell Grauffel, Cédric Scheer, Elisabeth Garnier, Jean-Marie Ye, Tao Chavant, Virginie Joint, Mathilde Esashi, Fumiko Dejaegere, Annick Gönczy, Pierre Tora, László |
author_sort | Fournier, Marjorie |
collection | PubMed |
description | Lysine acetylation is a widespread post-translational modification regulating various biological processes. To characterize cellular functions of the human lysine acetyltransferases KAT2A (GCN5) and KAT2B (PCAF), we determined their acetylome by shotgun proteomics. One of the newly identified KAT2A/2B substrate is polo-like kinase 4 (PLK4), a key regulator of centrosome duplication. We demonstrate that KAT2A/2B acetylate the PLK4 kinase domain on residues K45 and K46. Molecular dynamics modelling suggests that K45/K46 acetylation impairs kinase activity by shifting the kinase to an inactive conformation. Accordingly, PLK4 activity is reduced upon in vitro acetylation of its kinase domain. Moreover, the overexpression of the PLK4 K45R/K46R mutant in cells does not lead to centrosome overamplification, as observed with wild-type PLK4. We also find that impairing KAT2A/2B-acetyltransferase activity results in diminished phosphorylation of PLK4 and in excess centrosome numbers in cells. Overall, our study identifies the global human KAT2A/2B acetylome and uncovers that KAT2A/2B acetylation of PLK4 prevents centrosome amplification. |
format | Online Article Text |
id | pubmed-5095585 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-50955852016-11-18 KAT2A/KAT2B-targeted acetylome reveals a role for PLK4 acetylation in preventing centrosome amplification Fournier, Marjorie Orpinell, Meritxell Grauffel, Cédric Scheer, Elisabeth Garnier, Jean-Marie Ye, Tao Chavant, Virginie Joint, Mathilde Esashi, Fumiko Dejaegere, Annick Gönczy, Pierre Tora, László Nat Commun Article Lysine acetylation is a widespread post-translational modification regulating various biological processes. To characterize cellular functions of the human lysine acetyltransferases KAT2A (GCN5) and KAT2B (PCAF), we determined their acetylome by shotgun proteomics. One of the newly identified KAT2A/2B substrate is polo-like kinase 4 (PLK4), a key regulator of centrosome duplication. We demonstrate that KAT2A/2B acetylate the PLK4 kinase domain on residues K45 and K46. Molecular dynamics modelling suggests that K45/K46 acetylation impairs kinase activity by shifting the kinase to an inactive conformation. Accordingly, PLK4 activity is reduced upon in vitro acetylation of its kinase domain. Moreover, the overexpression of the PLK4 K45R/K46R mutant in cells does not lead to centrosome overamplification, as observed with wild-type PLK4. We also find that impairing KAT2A/2B-acetyltransferase activity results in diminished phosphorylation of PLK4 and in excess centrosome numbers in cells. Overall, our study identifies the global human KAT2A/2B acetylome and uncovers that KAT2A/2B acetylation of PLK4 prevents centrosome amplification. Nature Publishing Group 2016-10-31 /pmc/articles/PMC5095585/ /pubmed/27796307 http://dx.doi.org/10.1038/ncomms13227 Text en Copyright © 2016, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Fournier, Marjorie Orpinell, Meritxell Grauffel, Cédric Scheer, Elisabeth Garnier, Jean-Marie Ye, Tao Chavant, Virginie Joint, Mathilde Esashi, Fumiko Dejaegere, Annick Gönczy, Pierre Tora, László KAT2A/KAT2B-targeted acetylome reveals a role for PLK4 acetylation in preventing centrosome amplification |
title | KAT2A/KAT2B-targeted acetylome reveals a role for PLK4 acetylation in preventing centrosome amplification |
title_full | KAT2A/KAT2B-targeted acetylome reveals a role for PLK4 acetylation in preventing centrosome amplification |
title_fullStr | KAT2A/KAT2B-targeted acetylome reveals a role for PLK4 acetylation in preventing centrosome amplification |
title_full_unstemmed | KAT2A/KAT2B-targeted acetylome reveals a role for PLK4 acetylation in preventing centrosome amplification |
title_short | KAT2A/KAT2B-targeted acetylome reveals a role for PLK4 acetylation in preventing centrosome amplification |
title_sort | kat2a/kat2b-targeted acetylome reveals a role for plk4 acetylation in preventing centrosome amplification |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5095585/ https://www.ncbi.nlm.nih.gov/pubmed/27796307 http://dx.doi.org/10.1038/ncomms13227 |
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