title: The Drosophila mitotic inhibitor Frühstart specifically binds to the hydrophobic patch of cyclins.
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.
authors: ZMBH, Im Neuenheimer Feld 282, Heidelberg 69120, Germany.
authors: Pawel
authors: P
authors: Gawliński
authors: Rainer
authors: R
authors: Nikolay
authors: Catherine
authors: C
authors: Goursot
authors: Steffen
authors: S
authors: Lawo
authors: Bhagirath
authors: B
authors: Chaurasia
authors: Hans-Martin
authors: HM
authors: Herz
authors: Yvonne
authors: Y
authors: Kussler-Schneider
authors: Thomas
authors: T
authors: Ruppert
authors: Matthias
authors: M
authors: Mayer
authors: Jörg
authors: J
authors: Grosshans
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins / Q000378:metabolism*; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D016213:Cyclins / Q000737:chemistry / Q000378:metabolism*; D004330:Drosophila / Q000166:cytology / Q000378:metabolism*; D029721:Drosophila Proteins / Q000378:metabolism*; D057927:Hydrophobic and Hydrophilic Interactions; D008938:Mitosis; D016196:S Phase
chemical_list: D018797:Cell Cycle Proteins; D016213:Cyclins; D029721:Drosophila Proteins; C477649:Z600 protein, Drosophila; D018844:Cyclin-Dependent Kinases