1. The Drosophila mitotic inhibitor Frühstart specifically binds to the hydrophobic patch of cyclins
- Author
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Catherine Goursot, Jörg Großhans, Steffen Lawo, Hans-Martin Herz, Rainer Nikolay, Yvonne Kußler‐Schneider, Thomas Ruppert, Matthias P. Mayer, Pawel Gawliński, and Bhagirath Chaurasia
- Subjects
animal structures ,Scientific Report ,Mitosis ,Cell Cycle Proteins ,Biochemistry ,S Phase ,Histone H1 ,Cyclin-dependent kinase ,Cyclins ,Genetics ,Animals ,Drosophila Proteins ,Molecular Biology ,Cyclin ,Cyclin-dependent kinase 1 ,biology ,Kinase ,Cell cycle ,Cyclin-Dependent Kinases ,Mitotic inhibitor ,Cell biology ,biology.protein ,Drosophila ,biological phenomena, cell phenomena, and immunity ,Hydrophobic and Hydrophilic Interactions - 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 Fruhstart (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.
- Published
- 2006