Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 104, Issue 50, Pages 19867-19872Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0709879104
Keywords
cell cycle; cyclins; protein phosphatase; knockout; wee1
Categories
Funding
- NCI NIH HHS [P01 CA073992, P01 CA73992] Funding Source: Medline
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available