Guderian, Gernot. Control of centriole numbers by Plk4 autophosphorylation and Î²TrCP-mediated degradation. 2010, PhD Thesis, University of Basel, Faculty of Science.
Official URL: http://edoc.unibas.ch/diss/DissB_9277
Here, we show that human Plk4 is subject to beta-TrCP-dependent proteasomal degradation, indicating that this pathway is conserved from Drosophila to human (Cunha-Ferreira et al., 2009; Rogers et al., 2009). Unexpectedly, we found that stable overexpression of kinase-dead Plk4 leads to centriole overduplication. Our data indicate that this phenotype depends on the presence of endogenous wild-type Plk4 and that centriole overduplication results from disruption of Plk4 trans-autophosphorylation by kinase-dead Plk4, which then shields endogenous Plk4 from recognition by beta-TrCP. We conclude that active Plk4 promotes its own degradation by catalyzing beta-TrCP binding through trans-autophosphorylation within homodimers which has been independently confirmed by others (Holland et al., 2010). Additionally, we propose that Plk4 autophosphorylation is not sufficient for its degradation and that instead an additional kinase is required for this process.
|Advisors:||Nigg, Erich A.|
|Committee Members:||Spang, Anne and Hemmings, Brian A.|
|Faculties and Departments:||05 Faculty of Science > Departement Biozentrum > Growth & Development > Cell Biology (Nigg)|
|Bibsysno:||Link to catalogue|
|Number of Pages:||85 Bl.|
|Last Modified:||30 Jun 2016 10:41|
|Deposited On:||27 Dec 2010 10:35|
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