Identification of Cdk targets that control cytokinesis

The final event of the eukaryotic cell cycle is cytokinesis, when two new daughter cells are born. How the timing and execution of cytokinesis is controlled is poorly understood. Here, we show that downregulation of cyclin‐dependent kinase (Cdk) activity, together with upregulation of its counteract...

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Bibliographic Details
Published in:The EMBO journal 2015-01, Vol.34 (1), p.81-96
Main Authors: Kuilman, Thomas, Maiolica, Alessio, Godfrey, Molly, Scheidel, Noémie, Aebersold, Ruedi, Uhlmann, Frank
Format: Article
Language:English
Subjects:
Cdc14 phosphatase
Cell cycle
Cell Cycle Proteins - genetics
Cell Cycle Proteins - metabolism
Cyclin-dependent kinases
Cyclin-Dependent Kinases - genetics
Cyclin-Dependent Kinases - metabolism
Cytokines
cytokinesis
Cytokinesis - physiology
functional genomics
Microfilament Proteins - genetics
Microfilament Proteins - metabolism
mitosis
Phosphatase
phospho-proteomics
Phosphoproteins - genetics
Phosphoproteins - metabolism
Phosphorylation - physiology
Protein Tyrosine Phosphatases - genetics
Protein Tyrosine Phosphatases - metabolism
Proteome - genetics
Proteome - metabolism
Proteomics
Saccharomyces cerevisiae - genetics
Saccharomyces cerevisiae - metabolism
Saccharomyces cerevisiae Proteins - genetics
Saccharomyces cerevisiae Proteins - metabolism
Yeast
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Summary:The final event of the eukaryotic cell cycle is cytokinesis, when two new daughter cells are born. How the timing and execution of cytokinesis is controlled is poorly understood. Here, we show that downregulation of cyclin‐dependent kinase (Cdk) activity, together with upregulation of its counteracting phosphatase Cdc14, controls each of the sequential steps of cytokinesis, including furrow ingression, membrane resolution and cell separation in budding yeast. We use phosphoproteome analysis of mitotic exit to identify Cdk targets that are dephosphorylated at the time of cytokinesis. We then apply a new and widely applicable tool to generate conditionally phosphorylated proteins to identify those whose dephosphorylation is required for cytokinesis. This approach identifies Aip1, Ede1 and Inn1 as cytokinetic regulators. Our results suggest that cytokinesis is coordinately controlled by the master cell cycle regulator Cdk together with its counteracting phosphatase and that it is executed by concerted dephosphorylation of Cdk targets involved in several cell biological processes. Synopsis Cytokinesis and mitotic exit involves downregulation of cyclin‐dependent kinase (Cdk) activity and upregulation of counteracting phosphatases. Proteomic analyses of Cdk target phosphorylation during mitotic exit shows that Cdk and Cdc14 phosphatase coordinately control sequential steps of budding yeast cytokinesis. Cdk‐counteracting Cdc14 phosphatase controls cytokinetic processes such as furrow ingression, membrane resolution and cell separation. Phosphoproteome analysis reveals Cdk targets dephosphorylated at the time of cytokinesis. Constitutively phosphorylated proteins created via a conditional cyclin‐fusion strategy allows the study of targets whose dephosphorylation is required for cytokinesis. Aip1, Ede1 and Inn1 are identified and characterized as phospho‐regulated cytokinesis regulators through this approach. Phosphoproteomic analyses of mitotic exit reveals target proteins through which cyclin‐dependent kinase and its counteracting Cdc14 phosphatase control sequential steps of budding yeast cytokinesis.
ISSN:0261-4189
1460-2075
DOI:10.15252/embj.201488958