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

Files in This Item:
File Description SizeFormat 
PP1 initiates the dephosphorylation of MASTL, triggering mitotic .. DFey.pdf4.81 MBAdobe PDFDownload
Title: PP1 initiates the dephosphorylation of MASTL, triggering mitotic exit and bistability in human cells
Authors: Rogers, Samuel
Fey, Dirk
McCloy, Rachael A.
et al.
Permanent link: http://hdl.handle.net/10197/9750
Date: 1-Apr-2016
Online since: 2019-04-01T08:32:05Z
Abstract: 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.
Type of material: Journal Article
Publisher: The Company of Biologists
Journal: Journal of Cell Science
Volume: 129
Issue: 7
Start page: 1340
End page: 1354
Copyright (published version): 2016 the Authors
Keywords: MASTLDephosphorylationPP1Cdk1Pp2APhosphatase activity
DOI: 10.1242/jcs.179754
Language: en
Status of Item: Peer reviewed
Appears in Collections:SBI Research Collection

Show full item record

Citations 20

Last Week
Last month
checked on May 17, 2019

Google ScholarTM



This item is available under the Attribution-NonCommercial-NoDerivs 3.0 Ireland. No item may be reproduced for commercial purposes. For other possible restrictions on use please refer to the publisher's URL where this is made available, or to notes contained in the item itself. Other terms may apply.