Autophosphorylation of Polo-like Kinase 4 and Its Role in Centriole Duplication
| Autor: | Thierry Grand-Perret, James E. Sillibourne, An Boeckx, Nele Vloemans, Frederik Tack, Frans C. S. Ramaekers, Michel Bornens, Sathiesan Thambirajah, Pascal Bonnet |
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| Přispěvatelé: | Moleculaire Celbiologie, Genetica & Celbiologie, RS: CARIM School for Cardiovascular Diseases, RS: GROW - School for Oncology and Reproduction |
| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
PLK4
Proteasome Endopeptidase Complex Centriole Recombinant Fusion Proteins Molecular Sequence Data Cell Cycle Proteins Protein Serine-Threonine Kinases Biology Cell Line Serine Animals Humans Centrosome duplication Amino Acid Sequence Phosphorylation RNA Small Interfering Kinase activity Molecular Biology Mitosis Centrioles Centrosome Cell Cycle Autophosphorylation Articles Cell Biology Molecular biology Mutagenesis Site-Directed Centriole assembly |
| Zdroj: | Molecular Biology of the Cell Molecular Biology of the Cell, 21(4), 547-561. American Society for Cell Biology |
| ISSN: | 1939-4586 1059-1524 |
| Popis: | PLK4 is a key regulator of centriole duplication. Here, we show that PLK4 is active beyond the initiation of centriole duplication with the abundance of active kinase increasing to a peak in mitosis. Importantly, we show that differences in PLK4 abundance exist between mother and daughter centrioles and that active PLK4 is restricted to the centrosome. 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. |
| Databáze: | OpenAIRE |
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