Autophosphorylation of Polo-like Kinase 4 and Its Role in Centriole Duplication

James E. Sillibourne, Frederik Tack, Nele Vloemans, An Boeckx, Sathiesan Thambirajah, Pascal Bonnet, Frans C. S. Ramaekers, Michel Bornens*, Thierry Grand-Perret

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Centrosome duplication occurs once every cell cycle in a strictly controlled manner. Polo-like kinase 4 (PLK4) is a key regulator of this process whose kinase activity is essential for centriole duplication. Here, we show that PLK4 autophosphorylation of serine S305 is a consequence of kinase activation and enables the active fraction to be identified in the cell. Active PLK4 is detectable on the replicating mother centriole in G1/S, with the proportion of active kinase increasing through interphase to reach a maximum in mitosis. Activation of PLK4 at the replicating daughter centriole is delayed until G2, but a level equivalent to the replicating mother centriole is achieved in M phase. Active PLK4 is regulated by the proteasome, because either proteasome inhibition or mutation of the degron motif of PLK4 results in the accumulation of S305-phosphorylated PLK4. Autophosphorylation probably plays a role in the process of centriole duplication, because mimicking S305 phosphorylation enhances the ability of overexpressed PLK4 to induce centriole amplification. Importantly, we show that S305-phosphorylated PLK4 is specifically sequestered at the centrosome contrary to the nonphosphorylated form. These data suggest that PLK4 activity is restricted to the centrosome to prevent aberrant centriole assembly and sustained kinase activity is required for centriole duplication.
Original languageEnglish
Pages (from-to)547-561
JournalMolecular Biology of the Cell
Volume21
Issue number4
DOIs
Publication statusPublished - 15 Feb 2010

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