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PMID: 25371407 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Identification of Cdk targets that control cytokinesis.

The EMBO journal ·Vol. 34 ·No. 1 ·2015-01-02 ·Pages 81-96

Kuilman T, Maiolica A, Godfrey M, Scheidel N, Aebersold R, Uhlmann F

Abstract

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.

Keywords
Cdc14 phosphatase cytokinesis functional genomics mitosis phospho‐proteomics
MeSH Terms
Cell Cycle Proteins/genetics,metabolism Cyclin-Dependent Kinases/genetics,metabolism Cytokinesis/physiology Microfilament Proteins/genetics,metabolism Phosphoproteins/genetics,metabolism Phosphorylation/physiology Protein Tyrosine Phosphatases/genetics,metabolism Proteome/genetics,metabolism Saccharomyces cerevisiae/genetics,metabolism Saccharomyces cerevisiae Proteins/genetics,metabolism
Chemicals
CDC14 protein, S cerevisiae Cell Cycle Proteins Ede1 protein, S cerevisiae Inn1 protein, S cerevisiae Microfilament Proteins Phosphoproteins Proteome Saccharomyces cerevisiae Proteins actin interacting protein 1 Cyclin-Dependent Kinases Protein Tyrosine Phosphatases
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Kuilman Thomas
Chromosome Segregation Laboratory, Cancer Research UK London Research Institute Lincoln's Inn Fields Laboratories, London, UK [email protected] [email protected].
Maiolica Alessio
Department of Biology, Institute of Molecular Systems Biology, Eidgenössische Technische Hochschule (ETH) Zürich, Zurich, Switzerland.
Godfrey Molly
Chromosome Segregation Laboratory, Cancer Research UK London Research Institute Lincoln's Inn Fields Laboratories, London, UK.
Scheidel Noémie
Chromosome Segregation Laboratory, Cancer Research UK London Research Institute Lincoln's Inn Fields Laboratories, London, UK.
Aebersold Ruedi
Department of Biology, Institute of Molecular Systems Biology, Eidgenössische Technische Hochschule (ETH) Zürich, Zurich, Switzerland Faculty of Science, University of Zurich, Zurich, Switzerland.
Uhlmann Frank
Chromosome Segregation Laboratory, Cancer Research UK London Research Institute Lincoln's Inn Fields Laboratories, London, UK [email protected] [email protected].
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
1460-2075
DOI
10.15252/embj.201488958
Email
[email protected]
[email protected]
Published
2015-01-02
Epub
2014-00-04
Pages
81-96
Language
English
Region
England
NLM ID
8208664
PMCID
PMC4291482
Subset
IM
External Links
PubMed source DOI: 10.15252/embj.201488958 PMC Full Text View journal details
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