The Drosophila mitotic inhibitor Frühstart specifically binds to the hydrophobic patch of cyclins.
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.
Gawliński
Pawel
P
ZMBH, Im Neuenheimer Feld 282, Heidelberg 69120, Germany.
Nikolay
Rainer
R
Goursot
Catherine
C
Lawo
Steffen
S
Chaurasia
Bhagirath
B
Herz
Hans-Martin
HM
Kussler-Schneider
Yvonne
Y
Ruppert
Thomas
T
Mayer
Matthias
M
Grosshans
Jörg
J
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
D018797:Cell Cycle Proteins; D016213:Cyclins; D029721:Drosophila Proteins; C477649:Z600 protein, Drosophila; D018844:Cyclin-Dependent Kinases