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.
Kominami
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K
Laboratory of Cell Regulation, Imperial Cancer Research Fund, London, UK.
Ochotorena
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Toda
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D000595:Amino Acid Sequence; D018797:Cell Cycle Proteins / Q000378:metabolism*; D044842:Cullin Proteins; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors; D004791:Enzyme Inhibitors / Q000378:metabolism; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D016681:Genome, Fungal; D008969:Molecular Sequence Data; D009154:Mutation; D018384:Oxidative Stress; D010453:Peptide Synthases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D012260:Ribonucleases; D012261:Ribonucleoproteins / Q000378:metabolism*; D016196:S Phase; D044843:SKP Cullin F-Box Protein Ligases; D029701:Saccharomyces cerevisiae Proteins; D012568:Schizosaccharomyces / Q000235:genetics / Q000378:metabolism*; D029702:Schizosaccharomyces pombe Proteins; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*