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Nat Commun. 2016 Oct 31;7:13227. doi: 10.1038/ncomms13227.

KAT2A/KAT2B-targeted acetylome reveals a role for PLK4 acetylation in preventing centrosome amplification.

Fournier M1,2,3,4,5, Orpinell M6, Grauffel C1,2,3,4, Scheer E1,2,3,4, Garnier JM1,2,3,4, Ye T1,2,3,4, Chavant V1,2,3,4, Joint M1,2,3,4, Esashi F5, Dejaegere A1,2,3,4, Gönczy P6, Tora L1,2,3,4.

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Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), 67404 Illkirch, France.
Centre National de la Recherche Scientifique, UMR7104, 67404 Illkirch, France.
Institut National de la Santé et de la Recherche Médicale, U964, 67404 Illkirch, France.
Université de Strasbourg, 67404 Illkirch, France.
Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK.
Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Swiss Federal Institute of Technology Lausanne (EPFL), CH-1015 Lausanne, Switzerland.


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.

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