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Plk1 Regulates Activation of the Anaphase Promoting Complex by Phosphorylating and Triggering SCF βTrCP -dependent Destruction of the APC Inhibitor Emi1
Open accessAbstract
Progression through mitosis requires activation of cyclin B/Cdk1 and its downstream targets, including Polo-like kinase and the anaphase-promoting complex (APC), the ubiquitin ligase directing degradation of cyclins A and B. Recent evidence shows that APC activation requires destruction of the APC inhibitor Emi1. In prophase, phosphorylation of Emi1 generates a D-pS-G-X-X-pS degron to recruit the SCF βTrCP ubiquitin ligase, causing Emi1 destruction and allowing progression beyond prometaphase, but the kinases directing this phosphorylation remain undefined. We show here that the polo-like kinase Plk1 is strictly required for Emi1 destruction and that overexpression of Plk1 is sufficient to trigger Emi1 destruction. Plk1 stimulates Emi1 phosphorylation, βTrCP binding, and ubiquitination in vitro and cyclin B/Cdk1 enhances these effects. Plk1 binds to Emi1 in mitosis and the two proteins colocalize on the mitotic spindle poles, suggesting that Plk1 may spatially control Emi1 destruction. These data support the hypothesis that Plk1 activates the APC by directing the SCF-dependent destruction of Emi1 in prophase.
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Citations
Cited by
The anaphase promoting complex/cyclosome: a machine designed to destroy
Peters, J.-M. (2006) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1988 · Cited by 1,315
A Genome-wide RNAi Screen Identifies Multiple Synthetic Lethal Interactions with the Ras Oncogene
Luo, J., Emanuele, M. J., Li, D., Creighton, C. J., Schlabach, M. R., Westbrook, T. F., Wong, K.-K., & Elledge, S. J. (2009) · Cell · doi:10.1016/j.cell.2009.05.006 · Cited by 1,017
Polo on the Rise—from Mitotic Entry to Cytokinesis with Plk1
Petronczki, M., Lénárt, P., & Peters, J.-M. (2008) · Developmental Cell · doi:10.1016/j.devcel.2008.04.014 · Cited by 485
The predator becomes the prey: regulating the ubiquitin system by ubiquitylation and degradation
Weissman, A. M., Shabek, N., & Ciechanover, A. (2011) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3173 · Cited by 317
Peschiaroli, A., Dorrello, N. V., Guardavaccaro, D., Venere, M., Halazonetis, T., Sherman, N. E., & Pagano, M. (2006) · Molecular Cell · doi:10.1016/j.molcel.2006.06.013 · Cited by 289
Metadata
- Authors
- Hansen, D. V., Loktev, A. V., Ban, K. H., & Jackson, P. K.
- Venue
- Molecular Biology of the Cell
- Published
- 2004-12
- Volume
- 15
- Issue
- 12
- Pages
- 5623-5634
- ISSN
- 1059-1524 (ISSN-L)
- 1939-4586
- OpenAlex
- W2151784069
- Cited by
- 208
- References
- 0
- FWCI
- 5.94
- Type
- journal article
- Language
- en
- Open access
- green
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- Hansen, D. V., Loktev, A. V., Ban, K. H., & Jackson, P. K. (2004). Plk1 Regulates Activation of the Anaphase Promoting Complex by Phosphorylating and Triggering SCF βTrCP -dependent Destruction of the APC Inhibitor Emi1. Molecular Biology of the Cell. https://doi.org/10.1091/mbc.e04-07-0598
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