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PMID: 10582239 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

SCF ubiquitin protein ligases and phosphorylation-dependent proteolysis.

Willems AR, Goh T, Taylor L, Chernushevich I, Shevchenko A, Tyers M

Abstract

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.

MeSH Terms
Amino Acid Sequence Carrier Proteins Cell Cycle Cell Cycle Proteins/metabolism Cullin Proteins Cyclins/metabolism F-Box Proteins Fungal Proteins/metabolism Molecular Sequence Data Peptide Synthases/metabolism Phosphorylation SKP Cullin F-Box Protein Ligases Saccharomyces cerevisiae/enzymology Saccharomyces cerevisiae Proteins Sequence Homology, Amino Acid Substrate Specificity Ubiquitin-Protein Ligases
Chemicals
CLN2 protein, S cerevisiae Carrier Proteins Cdc53 protein, S cerevisiae Cell Cycle Proteins Cullin Proteins Cyclins F-Box Proteins Fungal Proteins Saccharomyces cerevisiae Proteins GRR1 protein, S cerevisiae SKP Cullin F-Box Protein Ligases Ubiquitin-Protein Ligases Peptide Synthases
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Willems A R
Programme in Molecular Biology and Cancer, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Canada.
Goh T
Taylor L
Chernushevich I
Shevchenko A
Tyers M
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Article Info
Journal
Philosophical transactions of the Royal Society of London. Series B, Biological sciences
Abbr.
Philos Trans R Soc Lond B Biol Sci
ISSN
0962-8436
Published
1999-09-29
Pages
1533-50
Language
English
Region
England
NLM ID
7503623
PMCID
PMC1692661
Subset
IM
Analysis Services
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