Overproduction of polypeptides corresponding to the amino terminus of the F-box proteins Cdc4p and Met30p inhibits ubiquitin ligase activities of their SCF complexes.

Ubiquitin ligases direct the transfer of ubiquitin onto substrate proteins and thus target the substrate for proteasome-dependent degradation. SCF complexes are a family of ubiquitin ligases composed of a common core of components and a variable component called an F-box protein that defines substrate specificity. Distinct SCF complexes, defined by ...
a particular F-box protein, target different substrate proteins for degradation. Although a few have been identified to be involved in important biological pathways, such as the cell division cycle and coordinating cellular responses to changes in environmental conditions, the role of the overwhelming majority of F-box proteins is not clear. Creating inhibitors that will block the in vivo activities of specific SCF ubiquitin ligases may provide identification of substrates of these uncharacterized F-box proteins. Using Saccharomyces cerevisiae as a model system, we demonstrate that overproduction of polypeptides corresponding to the amino terminus of the F-box proteins Cdc4p and Met30p results in specific inhibition of their SCF complexes. Analyses of mutant amino-terminal alleles demonstrate that the interaction of these polypeptides with their full-length counterparts is an important step in the inhibitory process. These results suggest a common means to inhibit specific SCF complexes in vivo.
Mesh Terms:
Base Sequence, Cell Cycle Proteins, Cysteine Endopeptidases, DNA Primers, Eukaryotic Cells, F-Box Proteins, Gene Expression Regulation, Enzymologic, Gene Expression Regulation, Fungal, Macromolecular Substances, Multienzyme Complexes, Mutation, Peptide Synthases, Peptides, Proteasome Endopeptidase Complex, Protein Structure, Tertiary, Repressor Proteins, SKP Cullin F-Box Protein Ligases, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Ubiquitin, Ubiquitin-Protein Ligase Complexes, Ubiquitin-Protein Ligases
Eukaryotic Cell
Date: Feb. 01, 2003
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