The meiosis-specific protein kinase Ime2 triggers Cdh1
phosphorylation and inactivation of the anaphase-promoting
complex.
Melanie Bolte, Patrick Steigemann, Patrick
Dieckhoff, Gerhard H. Braus, Stefan Irniger
Dept. of Mol.
Microbiology, Inst of Microbiology& Genetics, Grisebachstr. 8,
Göttingen, D-37077, Germany
The anaphase-promoting complex/cyclosome
(APC/C) is a multisubunit ubiquitin ligase essential for mitotic and
meiotic cell divisions. APC/C activity is tightly controlled during the
cell cycle. In a screening for regulators of APC/C, we have identified
the meiosis-specific protein kinase Ime2. We found that ectopic
expression of IME2 in mitotic cells results in the inhibition of
APC-mediated proteolysis. IME2 expressed in G1 arrested cells
prevented degradation of mitotic cyclins and partially stabilised
securin Pds1 and polo kinase Cdc5, two other APC substrates. IME2
expression in G1 cells resulted in the phosphorylation of Cdh1. These
data suggest that Ime2 and cyclin-dependent kinase Cdk1 regulate APC-Cdh1 in a similar manner, by Cdh1 phosphorylation, thereby causing its
dissociation from APC/C and inactivation of the ubiquitin ligase. Our
findings support the model suggesting that Ime2 replaces the G1-specific
Cdk1, Cdk1/Cln, during meiosis. However, Ime2 is unable to take over all
the functions of Cdk1/Cln in triggering the initiation of DNA
replication and in contrast to Cdk1/Cln, Ime2 inhibits budding. The
expression of Ime2 caused cells to arrest as unbudded cells containing
replicated DNA and elongated spindles. Ime2 is itself an unstable
protein which was not stabilised in mutants of the APC and SCF
ubiquitin-ligases. In our current projects we focus on the mechanisms of
Ime2 proteolysis and on the relevance of Ime2 instability during the
meiotic cell cycle.
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