SCF ubiquitin protein ligases and phosphorylation-dependent proteolysis.
Many key activators and inhibitors of cell division are targeted for degradation by a recently described family of E3 ubiquitin protein ligases termed Skp1-Cdc53-F-box protein (SCF) complexes. SCF complexes physically link substrate proteins to the E2 ubiquitin-conjugating enzyme Cdc34, which catalyses substrate ubiquitination, leading to subsequent degradation by the 26S proteasome. SCF complexes contain a variable subunit called an F-box protein that confers substrate specificity on an invariant core complex composed of the subunits Cdc34, Skp1 and Cdc53. Here, we review the substrates and pathways regulated by the yeast F-box proteins Cdc4, Grr1 and Met30. The concepts of SCF ubiquitin ligase function are illustrated by analysis of the degradation pathway for the G1 cyclin Cln2. Through mass spectrometric analysis of Cdc53 associated proteins, we have identified three novel F-box proteins that appear to participate in SCF-like complexes. As many F-box proteins can be found in sequence databases, it appears that a host of cellular pathways will be regulated by SCF-dependent proteolysis.
Willems
A R
AR
Programme in Molecular Biology and Cancer, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Canada.
Goh
T
T
Taylor
L
L
Chernushevich
I
I
Shevchenko
A
A
Tyers
M
M
D000595:Amino Acid Sequence; D002352:Carrier Proteins; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000378:metabolism*; D044842:Cullin Proteins; D016213:Cyclins / Q000378:metabolism; D044783:F-Box Proteins; D005656:Fungal Proteins / Q000378:metabolism; D008969:Molecular Sequence Data; D010453:Peptide Synthases / Q000378:metabolism*; D010766:Phosphorylation; D044843:SKP Cullin F-Box Protein Ligases; D012441:Saccharomyces cerevisiae / Q000201:enzymology; D029701:Saccharomyces cerevisiae Proteins; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity; D044767:Ubiquitin-Protein Ligases
C082721:CLN2 protein, S cerevisiae; D002352:Carrier Proteins; C100988:Cdc53 protein, S cerevisiae; D018797:Cell Cycle Proteins; D044842:Cullin Proteins; D016213:Cyclins; D044783:F-Box Proteins; D005656:Fungal Proteins; D029701:Saccharomyces cerevisiae Proteins; C071032:GRR1 protein, S cerevisiae; D044843:SKP Cullin F-Box Protein Ligases; D044767:Ubiquitin-Protein Ligases; D010453:Peptide Synthases