The Drosophila mitotic inhibitor Frühstart specifically binds to the hydrophobic patch of cyclins

Pawel Gawliński; Rainer Nikolay; Catherine Goursot; Steffen Lawo; Bhagirath Chaurasia; Hans-Martin Herz; Yvonne Kussler-Schneider; Thomas Ruppert; Matthias Mayer; Jörg Grosshans

doi:10.1038/sj.embor.7400948

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The Drosophila mitotic inhibitor Frühstart specifically binds to the hydrophobic patch of cyclins

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The Drosophila mitotic inhibitor Frühstart specifically binds to the hydrophobic patch of cyclins

Pawel Gawliński, Rainer Nikolay, Catherine Goursot, Steffen Lawo, Bhagirath Chaurasia, Hans-Martin Herz, Yvonne Kussler-Schneider, Thomas Ruppert, Matthias Mayer and Jörg Grosshans

EMBO reports, Vol.8(5), pp.490-496

05/2007

DOI: 10.1038/sj.embor.7400948

PMCID: PMC1866202

PMID: 17431409

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Abstract

The hydrophobic patch of cyclins interacts with cyclin-dependent kinase (Cdk) substrates and p27-type Cdk inhibitors. Although this interaction is assumed to contribute to the specificity of different Cdk-Cyclin complexes, its role in specific steps of the cell cycle has not been demonstrated. Here, we show that in Drosophila the mitotic inhibitor Frühstart (Frs) binds specifically and with high affinity to the hydrophobic patch of cyclins. In contrast to p27-type Cdk inhibitors, Frs does not form a stable interaction with the catalytic centre of Cdk and allows phosphorylation of generic model substrates, such as histone H1. Consistent with a 2.5 times stronger binding to CycA than to CycE in vitro, ectopic expression of frs induces endocycles, in a manner similar to that reported previously for downregulation of CycA or Cdk1. We propose that binding of Frs to cyclins blocks the hydrophobic patch to interfere with Cdk1 substrate recognition.

Mitosis

Animals

Cell Cycle Proteins - metabolism

Cyclin-Dependent Kinases - metabolism

Cyclins - chemistry

Cyclins - metabolism

Drosophila - cytology

Drosophila - metabolism

Drosophila Proteins - metabolism

Hydrophobic and Hydrophilic Interactions

S Phase

Details

Title: Subtitle: The Drosophila mitotic inhibitor Frühstart specifically binds to the hydrophobic patch of cyclins
Creators: Pawel Gawliński - Heidelberg University
Rainer Nikolay - Heidelberg University
Catherine Goursot - Heidelberg University
Steffen Lawo - Heidelberg University
Bhagirath Chaurasia - Heidelberg University
Hans-Martin Herz - Heidelberg University
Yvonne Kussler-Schneider - Heidelberg University
Thomas Ruppert - Heidelberg University
Matthias Mayer - Heidelberg University
Jörg Grosshans - Heidelberg University
Resource Type: Journal article
Publication Details: EMBO reports, Vol.8(5), pp.490-496
DOI: 10.1038/sj.embor.7400948
PMID: 17431409
PMCID: PMC1866202
NLM abbreviation: EMBO Rep
ISSN: 1469-221X
eISSN: 1469-3178
Language: English
Date published: 05/2007
Academic Unit: Fraternal Order of Eagles Diabetes Research Center; Endocrinology and Metabolism; Internal Medicine
Record Identifier: 9984359768902771

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