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PP1 initiates the dephosphorylation of MASTL, triggering mitotic exit and bistability in human cells

Rogers, Samuel; Fey, Dirk; McCloy, Rachael A.; Parker, Benjamin L.; Mitchell, Nicholas J.; Payne, Richard J.; Daly, Roger J.; James, David E.; Caldon, C. Elizabeth; Watkins, D. Neil; Croucher, David R.; Burgess, Andrew


Samuel Rogers

Dirk Fey

Rachael A. McCloy

Benjamin L. Parker

Richard J. Payne

Roger J. Daly

David E. James

C. Elizabeth Caldon

D. Neil Watkins

David R. Croucher

Andrew Burgess


Entry into mitosis is driven by the phosphorylation of thousands of substrates, under the master control of Cdk1. During entry into mitosis, Cdk1, in collaboration with MASTL kinase, represses the activity of the major mitotic protein phosphatases, PP1 and PP2A, thereby ensuring mitotic substrates remain phosphorylated. For cells to complete and exit mitosis, these phosphorylation events must be removed, and hence, phosphatase activity must be reactivated. This reactivation of phosphatase activity presumably requires the inhibition of MASTL; however, it is not currently understood what deactivates MASTL and how this is achieved. In this study, we identified that PP1 is associated with, and capable of partially dephosphorylating and deactivating, MASTL during mitotic exit. Using mathematical modelling, we were able to confirm that deactivation of MASTL is essential for mitotic exit. Furthermore, small decreases in Cdk1 activity during metaphase are sufficient to initiate the reactivation of PP1, which in turn partially deactivates MASTL to release inhibition of PP2A and, hence, create a feedback loop. This feedback loop drives complete deactivation of MASTL, ensuring a strong switch-like activation of phosphatase activity during mitotic exit.


Rogers, S., Fey, D., McCloy, R. A., Parker, B. L., Mitchell, N. J., Payne, R. J., …Burgess, A. (2016). PP1 initiates the dephosphorylation of MASTL, triggering mitotic exit and bistability in human cells. Journal of Cell Science, 129(7), 1340-1354.

Journal Article Type Article
Acceptance Date Feb 8, 2016
Online Publication Date Feb 12, 2016
Publication Date Apr 1, 2016
Deposit Date Nov 20, 2018
Publicly Available Date Jan 22, 2019
Journal Journal of Cell Science
Print ISSN 0021-9533
Electronic ISSN 1477-9137
Publisher Company of Biologists
Peer Reviewed Peer Reviewed
Volume 129
Issue 7
Pages 1340-1354
Keywords Cell Biology
Public URL
Publisher URL


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