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

Abstract

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 SCF^Pop1,2, 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, SCF^Pop1/Pop1, SCF^Pop1/Pop2 and SCF^Pop2/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.