Two F-box/WD-repeat proteins Pop1 and Pop2 form hetero- and homo-complexes together with cullin-1 in the fission yeast SCF (Skp1-Cullin-1-F-box) ubiquitin ligase

Background: In the ubiquitin-dependent proteolysis pathway, a ubiquitin ligase (E3) is responsible for substrate selectivity and timing of degradation. A novel E3, SCF (Skp1-Cullin-1/Cdc53-F-box) plays a pivotal role in cell cycle progression. In fission yeast, F-box/WD-repeat protein Pop1 regulates the level of the CDK (cyclin-dependent kinase) inhibitor Rum1 and the S phase regulator Cdc18, Results: We have cloned and characterized the pop2(+) gene which encodes the Pop1-related F-box/WD-repeat protein. Pop2 plays a role which overlaps with Pop1 in the degradation of Rum1 and Cdc18, However, these two proteins are not functional homologues, Pop1 and Pop2 form hetero- as well as homo-dimers in the cell. We have analysed two fission yeast cullin members and found that cullin-1 functions as a component of SCFPop1,2, whilst cullin-3 is involved in the distinct stress-response pathway. Conclusions: Fission yeast SCF is composed of Pop1 and Pop2, two structurally related but functionally independent F-box/WD-repeat proteins, By forming three distinct complexes, SCFPop1/Pop1, SCFPop1/Pop2 and SCFPop2/Pop2, SCF has evolved a sophisticated mechanism to control the level of Rum1 and Cdc18, Fission yeast SCF also contains cullin-1 as a universal scaffold and each cullin member plays a distinct biological role.