Title: Control of mitotic exit by PP2A regulation of Cdc25C and Cdk1
Authors: Forester, Craig M
Maddox, Jessica
Louis, Justin Vijay
Goris, Jozef
Virshup, David M # ×
Issue Date: Dec-2007
Publisher: Natl acad sciences
Series Title: Proceedings of the National Academy of Sciences of the United States of America vol:104 issue:50 pages:19867-19872
Abstract: inactivation of maturation-promoting factor [(MPF) Cdk1/Cyclin B] is a key event in the exit from mitosis. Although degradation of Cyclin B is important for MPF inactivation, recent studies indicate that Cdk1 phosphorylation and inactivation occur before Cyclin B degradation and, therefore, also may be important steps in the exit from mitosis. Cdk1 activity is controlled by the Cdc25C phosphatase, which is turned on at the G(2)/M transition to catalyze Cdk1 activation. PP2A:B56 delta is a negative regulator of Cdc25C during interphase. We show here that PP2A:B56 delta also regulates Cdc25C at mitosis. Failure of MA:113566 to dephosphorylate Cdc25C at mitosis results in prolonged hyperphosphorylation and activation of Cdc25C, causing persistent dephosphorylation and, hence, activation of Cdk1. This constitutive activation of Cdc25C and Cdk1 leads to a delayed exit from mitosis. Consistent with Cdk1 as a major biological target of B56 delta, stable knockdown and germ-line mouse KO of B56 delta leads to compensatory transcriptional up-regulation of Wee1 kinase to oppose the Cdc25C activity and permit cell survival. These observations place PP2A:B56 delta as a key upstream regulator of Cdk1 activity upon exit from mitosis.
ISSN: 0027-8424
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Protein Phosphorylation and Proteomics
× corresponding author
# (joint) last author

Files in This Item:

There are no files associated with this item.

Request a copy


All items in Lirias are protected by copyright, with all rights reserved.

© Web of science