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Ordered proteolysis in anaphase inactivates Plk1 to contribute to proper mitotic exit in human cells
Open accessAbstract
We have found that key mitotic regulators show distinct patterns of degradation during exit from mitosis in human cells. Using a live-cell assay for proteolysis, we show that two of these regulators, polo-like kinase 1 (Plk1) and Aurora A, are degraded at different times after the anaphase-promoting complex/cyclosome (APC/C) switches from binding Cdc20 to Cdh1. Therefore, events in addition to the switch from Cdc20 to Cdh1 control the proteolysis of APC/CCdh1 substrates in vivo. We have identified a putative destruction box in Plk1 that is required for degradation of Plk1 in anaphase, and have examined the effect of nondegradable Plk1 on mitotic exit. Our results show that Plk1 proteolysis contributes to the inactivation of Plk1 in anaphase, and that this is required for the proper control of mitotic exit and cytokinesis. Our experiments reveal a role for APC/C-mediated proteolysis in exit from mitosis in human cells.
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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
The Cdc14B-Cdh1-Plk1 Axis Controls the G2 DNA-Damage-Response Checkpoint
Bassermann, F., Frescas, D., Guardavaccaro, D., Busino, L., Peschiaroli, A., & Pagano, M. (2008) · Cell · doi:10.1016/j.cell.2008.05.043 · Cited by 397
Frank, C. L., & Tsai, L.-H. (2009) · Neuron · doi:10.1016/j.neuron.2009.03.029 · Cited by 118
Spardy, N., Covella, K., Cha, E., Hoskins, E. E., Wells, S. I., Duensing, A., & Duensing, S. (2009) · Cancer Research · doi:10.1158/0008-5472.can-09-0925 · Cited by 91
Sequential replication-coupled destruction at G1/S ensures genome stability
Coleman, K. E., Grant, G. D., Haggerty, R. A., Brantley, K., Shibata, E., Workman, B. D., Dutta, A., Varma, D., Purvis, J. E., & Cook, J. G. (2015) · Genes & Development · doi:10.1101/gad.263731.115 · Cited by 51
Cullin 3, a cellular scripter of the non-proteolytic ubiquitin code
Jerabkova, K., & Sumara, I. (2019) · Seminars in Cell & Developmental Biology · doi:10.1016/j.semcdb.2018.12.007 · Cited by 33
Interaction of IRS2 with PLK1 protects cells from mitotic stress
Lee, J.-S., Bui, Q. T., Jo, M., Morgan, J. S., Nasa, I., Kettenbach, A. N., & Shaw, L. M. (2026) · Cell Death & Disease · doi:10.1038/s41419-026-08706-0 · Cited by 1
Metadata
- Authors
- Lindon, C., & Pines, J.
- Venue
- The Journal of Cell Biology
- Publisher
- Rockefeller University Press
- Published
- 2004-01-19
- Volume
- 164
- Issue
- 2
- Pages
- 233-241
- ISSN
- 0021-9525 (ISSN-L)
- 1540-8140
- OpenAlex
- W1969761431
- Cited by
- 356
- References
- 0
- FWCI
- 6.53
- Type
- journal article
- Language
- en
- Open access
- green
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