APC(ste9/srw1) promotes degradation of mitotic cyclins in G(1) and is inhibited by cdc2 phosphorylation.

Fission yeast ste9/srw1 is a WD-repeat protein highly homologous to budding yeast Hct1/Cdh1 and Drosophila Fizzy-related that are involved in activating APC/C (anaphase-promoting complex/cyclosome). We show that APC(ste9/srw1) specifically promotes the degradation of mitotic cyclins cdc13 and cig1 but not the S-phase cyclin cig2. APC(ste9/srw1) is not necessary for the proteolysis of cdc13 and cig1 that occurs at the metaphase-anaphase transition but it is absolutely required for their degradation in G(1). Therefore, we propose that the main role of APC(ste9/srw1) is to promote degradation of mitotic cyclins when cells need to delay or arrest the cell cycle in G(1). We also show that ste9/srw1 is negatively regulated by cdc2-dependent protein phosphorylation. In G(1), when cdc2-cyclin kinase activity is low, unphosphorylated ste9/srw1 interacts with APC/C. In the rest of the cell cycle, phosphorylation of ste9/srw1 by cdc2-cyclin complexes both triggers proteolysis of ste9/srw1 and causes its dissociation from the APC/C. This mechanism provides a molecular switch to prevent inactivation of cdc2 in G(2) and early mitosis and to allow its inactivation in G(1).