title: The Mitotic Exit Network and Cdc14 phosphatase initiate cytokinesis by counteracting CDK phosphorylations and blocking polarised growth.
abstract: Polarisation of the actin cytoskeleton must cease during cytokinesis, to support efficient assembly and contraction of the actomyosin ring at the site of cell division, but the underlying mechanisms are still understood poorly in most species. In budding yeast, the Mitotic Exit Network (MEN) releases Cdc14 phosphatase from the nucleolus during anaphase, leading to the inactivation of mitotic forms of cyclin-dependent kinase (CDK) and the onset of septation, before G1-CDK can be reactivated and drive re-polarisation of the actin cytoskeleton to a new bud. Here, we show that premature inactivation of mitotic CDK, before release of Cdc14, allows G1-CDK to divert the actin cytoskeleton away from the actomyosin ring to a new site of polarised growth, thereby delaying progression through cytokinesis. Our data indicate that cells normally avoid this problem via the MEN-dependent release of Cdc14, which counteracts all classes of CDK-mediated phosphorylations during cytokinesis and blocks polarised growth. The dephosphorylation of CDK targets is therefore central to the mechanism by which the MEN and Cdc14 initiate cytokinesis and block polarised growth during late mitosis.
authors.affiliation: Paterson Institute for Cancer Research, University of Manchester, Manchester, UK.
authors.forename: Alberto
authors.initials: A
authors.lastname: Sanchez-Diaz
authors.forename: Pedro Junior
authors.initials: PJ
authors.lastname: Nkosi
authors.forename: Stephen
authors.initials: S
authors.lastname: Murray
authors.forename: Karim
authors.initials: K
authors.lastname: Labib
mesh_terms: D018797:Cell Cycle Proteins / Q000502:physiology*; D018844:Cyclin-Dependent Kinases / Q000502:physiology*; D048749:Cytokinesis; D005656:Fungal Proteins / Q000502:physiology*; D008938:Mitosis; D010766:Phosphorylation; D017027:Protein Tyrosine Phosphatases / Q000502:physiology*; D004718:Saccharomycetales / Q000502:physiology*
chemical_list: D018797:Cell Cycle Proteins; D005656:Fungal Proteins; D018844:Cyclin-Dependent Kinases; D017027:Protein Tyrosine Phosphatases