title: Nur1 dephosphorylation confers positive feedback to mitotic exit phosphatase activation in budding yeast.
abstract: 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.
authors.affiliation: Chromosome Segregation Laboratory, Cancer Research UK London Research Institute, London, United Kingdom.
authors.forename: Molly
authors.initials: M
authors.lastname: Godfrey
authors.affiliation: Chromosome Segregation Laboratory, Cancer Research UK London Research Institute, London, United Kingdom.
authors.forename: Thomas
authors.initials: T
authors.lastname: Kuilman
authors.affiliation: Chromosome Segregation Laboratory, Cancer Research UK London Research Institute, London, United Kingdom.
authors.forename: Frank
authors.initials: F
authors.lastname: Uhlmann
mesh_terms: D000705:Anaphase; D002453:Cell Cycle / Q000235:genetics; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D020090:Chromosome Segregation / Q000235:genetics*; D025461:Feedback, Physiological; D008565:Membrane Proteins / Q000235:genetics*; D008938:Mitosis / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D010766:Phosphorylation / Q000235:genetics; D017027:Protein Tyrosine Phosphatases / Q000235:genetics* / Q000378:metabolism; D012441:Saccharomyces cerevisiae; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics
chemical_list: C074860:CDC14 protein, S cerevisiae; D018797:Cell Cycle Proteins; D008565:Membrane Proteins; C119300:Net1 protein, S cerevisiae; D009687:Nuclear Proteins; C000599015:Nur1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D017027:Protein Tyrosine Phosphatases