Nur1 dephosphorylation confers positive feedback to mitotic exit phosphatase activation in budding yeast.

Substrate dephosphorylation by the cyclin-dependent kinase (Cdk)-opposing phosphatase, Cdc14, is vital for many events during budding yeast mitotic exit. Cdc14 is sequestered in the nucleolus through inhibitory binding to Net1, from which it is released in anaphase following Net1 phosphorylation. In...

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Main Authors: Molly Godfrey, Thomas Kuilman, Frank Uhlmann
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2015-01-01
Series:PLoS Genetics
Online Access:http://europepmc.org/articles/PMC4287440?pdf=render
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author Molly Godfrey
Thomas Kuilman
Frank Uhlmann
author_facet Molly Godfrey
Thomas Kuilman
Frank Uhlmann
author_sort Molly Godfrey
collection DOAJ
description Substrate dephosphorylation by the cyclin-dependent kinase (Cdk)-opposing phosphatase, Cdc14, is vital for many events during budding yeast mitotic exit. Cdc14 is sequestered in the nucleolus through inhibitory binding to Net1, from which it is released in anaphase following Net1 phosphorylation. Initial Net1 phosphorylation depends on Cdk itself, in conjunction with proteins of the Cdc14 Early Anaphase Release (FEAR) network. Later on, the Mitotic Exit Network (MEN) signaling cascade maintains Cdc14 release. An important unresolved question is how Cdc14 activity can increase in early anaphase, while Cdk activity, that is required for Net1 phosphorylation, decreases and the MEN is not yet active. Here we show that the nuclear rim protein Nur1 interacts with Net1 and, in its Cdk phosphorylated form, inhibits Cdc14 release. Nur1 is dephosphorylated by Cdc14 in early anaphase, relieving the inhibition and promoting further Cdc14 release. Nur1 dephosphorylation thus describes a positive feedback loop in Cdc14 phosphatase activation during mitotic exit, required for faithful chromosome segregation and completion of the cell division cycle.
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spelling doaj.art-f27567ce0fb44b77a61ebc06262b23ab2022-12-21T21:43:55ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042015-01-01111e100490710.1371/journal.pgen.1004907Nur1 dephosphorylation confers positive feedback to mitotic exit phosphatase activation in budding yeast.Molly GodfreyThomas KuilmanFrank UhlmannSubstrate dephosphorylation by the cyclin-dependent kinase (Cdk)-opposing phosphatase, Cdc14, is vital for many events during budding yeast mitotic exit. Cdc14 is sequestered in the nucleolus through inhibitory binding to Net1, from which it is released in anaphase following Net1 phosphorylation. Initial Net1 phosphorylation depends on Cdk itself, in conjunction with proteins of the Cdc14 Early Anaphase Release (FEAR) network. Later on, the Mitotic Exit Network (MEN) signaling cascade maintains Cdc14 release. An important unresolved question is how Cdc14 activity can increase in early anaphase, while Cdk activity, that is required for Net1 phosphorylation, decreases and the MEN is not yet active. Here we show that the nuclear rim protein Nur1 interacts with Net1 and, in its Cdk phosphorylated form, inhibits Cdc14 release. Nur1 is dephosphorylated by Cdc14 in early anaphase, relieving the inhibition and promoting further Cdc14 release. Nur1 dephosphorylation thus describes a positive feedback loop in Cdc14 phosphatase activation during mitotic exit, required for faithful chromosome segregation and completion of the cell division cycle.http://europepmc.org/articles/PMC4287440?pdf=render
spellingShingle Molly Godfrey
Thomas Kuilman
Frank Uhlmann
Nur1 dephosphorylation confers positive feedback to mitotic exit phosphatase activation in budding yeast.
PLoS Genetics
title Nur1 dephosphorylation confers positive feedback to mitotic exit phosphatase activation in budding yeast.
title_full Nur1 dephosphorylation confers positive feedback to mitotic exit phosphatase activation in budding yeast.
title_fullStr Nur1 dephosphorylation confers positive feedback to mitotic exit phosphatase activation in budding yeast.
title_full_unstemmed Nur1 dephosphorylation confers positive feedback to mitotic exit phosphatase activation in budding yeast.
title_short Nur1 dephosphorylation confers positive feedback to mitotic exit phosphatase activation in budding yeast.
title_sort nur1 dephosphorylation confers positive feedback to mitotic exit phosphatase activation in budding yeast
url http://europepmc.org/articles/PMC4287440?pdf=render
work_keys_str_mv AT mollygodfrey nur1dephosphorylationconferspositivefeedbacktomitoticexitphosphataseactivationinbuddingyeast
AT thomaskuilman nur1dephosphorylationconferspositivefeedbacktomitoticexitphosphataseactivationinbuddingyeast
AT frankuhlmann nur1dephosphorylationconferspositivefeedbacktomitoticexitphosphataseactivationinbuddingyeast