Ubiquitination and Degradation of the Substrate Recognition Subunits of SCF Ubiquitin–Protein Ligases

• Published in: Molecular cell Vol. 2; no. 5; pp. 571 - 580
• Main Authors: Zhou, Pengbo, Howley, Peter M
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.11.1998
• Subjects: Anaphase-Promoting Complex-Cyclosome; Carrier Proteins; CDC28 Protein Kinase, S cerevisiae - genetics; CDC28 Protein Kinase, S cerevisiae - physiology; Cell Cycle - drug effects; Cell Cycle - genetics; Cell Cycle Proteins - genetics; Cell Cycle Proteins - metabolism; Cullin Proteins; Cyclins - metabolism; Cysteine Endopeptidases - genetics; Cysteine Endopeptidases - metabolism; F-Box Proteins; Fungal Proteins - genetics; Fungal Proteins - metabolism; Half-Life; Hydroxyurea - pharmacology; Ligases - genetics; Ligases - metabolism; Ligases - physiology; Lipoproteins - pharmacology; Multienzyme Complexes - genetics; Multienzyme Complexes - metabolism; Mutation; Nocodazole - pharmacology; Pheromones; Precipitin Tests; Proteasome Endopeptidase Complex; Recombinant Fusion Proteins - metabolism; S-Phase Kinase-Associated Proteins; Saccharomyces cerevisiae; Saccharomyces cerevisiae - drug effects; Saccharomyces cerevisiae - enzymology; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae - metabolism; Saccharomyces cerevisiae Proteins; Substrate Specificity; Ubiquitin-Protein Ligase Complexes; Ubiquitin-Protein Ligases; Ubiquitins - metabolism
• ISSN: 1097-2765; 1097-4164; 1097-4164
• DOI: 10.1016/S1097-2765(00)80156-2

The S. cerevisiae SCF Cdc4p ubiquitin–protein ligase complex promotes cell cycle transitions through degradation of cell cycle regulators. To investigate SCF Cdc4p regulation in vivo, we examined the stability of individual SCF Cdc4p components. Whereas Cdc53p and Skp1p were stable, Cdc4p, the F box–containing component responsible for substrate recognition, was short lived and subject to SCF-mediated ubiquitination. Grr1p, another F box component of SCF complexes, was also ubiquitinated. A stable truncated Cdc4p F-β-gal hybrid protein capable of binding Skp1p and entering into an SCF complex interfered with proteolysis of SCF targets and inhibited cell proliferation. The finding that the F box–containing SCF components are unstable suggests a mechanism of regulating SCF function through ubiquitination and proteolysis of F box components.