APCste9/srw1promotes degradation of mitotic cyclins in G1and is inhibited by cdc2 phosphorylation

Open Access
Publisher Website
Google Scholar
Abstract
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 APCste9/srw1 specifically promotes the degradation of mitotic cyclins cdc13 and cig1 but not the S‐phase cyclin cig2. APCste9/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 G1. Therefore, we propose that the main role of APCste9/srw1 is to promote degradation of mitotic cyclins when cells need to delay or arrest the cell cycle in G1. We also show that ste9/srw1 is negatively regulated by cdc2‐dependent protein phosphorylation. In G1, 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 G2 and early mitosis and to allow its inactivation in G1.