Signal-Induced Disassembly of the SCF Ubiquitin Ligase Complex by Cdc48/p97

• Published in: Molecular cell Vol. 48; no. 2; pp. 288 - 297
• Main Authors: Yen, James L., Flick, Karin, Papagiannis, Christie V., Mathur, Radhika, Tyrrell, An, Ouni, Ikram, Kaake, Robyn M., Huang, Lan, Kaiser, Peter
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 26.10.2012
• Subjects: Adenosine Triphosphatases - genetics; Adenosine Triphosphatases - metabolism; Adenosine Triphosphate - metabolism; adenosinetriphosphatase; cadmium; Cadmium - pharmacology; Cell Cycle Proteins - genetics; Cell Cycle Proteins - metabolism; dissociation; F-box proteins; F-Box Proteins - genetics; F-Box Proteins - metabolism; Hydrolysis - drug effects; Multiprotein Complexes - chemistry; Multiprotein Complexes - metabolism; Protein Binding; Saccharomyces cerevisiae - enzymology; Saccharomyces cerevisiae Proteins - metabolism; Signal Transduction; SKP Cullin F-Box Protein Ligases - genetics; SKP Cullin F-Box Protein Ligases - metabolism; Substrate Specificity; ubiquitin-protein ligase; Ubiquitination; Valosin Containing Protein; yeasts
• ISSN: 1097-2765; 1097-4164; 1097-4164
• DOI: 10.1016/j.molcel.2012.08.015

A large group of E3 ubiquitin ligases is formed by the multisubunit SCF complex, whose core complex (Rbx1/Cul1-Cdc53/Skp1) binds one of many substrate recruiting F-box proteins to form an array of SCF ligases with diverse substrate specificities. It has long been thought that ubiquitylation by SCF ligases is regulated at the level of substrate binding. Here we describe an alternative mechanism of SCF regulation by active dissociation of the F-box subunit. We show that cadmium stress induces selective recruitment of the AAA+ ATPase Cdc48/p97 to catalyze dissociation of the F-box subunit from the yeast SCFMet30 ligase to block substrate ubiquitylation and trigger downstream events. Our results not only provide an additional layer of ubiquitin ligase regulation but also suggest that targeted, signal-dependent dissociation of multisubunit enzyme complexes is an important mechanism in control of enzyme function. [Display omitted] ► Stress induced SCFMet30 autoubiquitylation is recruitment signal for Cdc48 ► Active disassembly of SCFMet30 by Cdc48 to inhibit ubiquitin ligase activity ► ATPase activity is required for F-box dissociation from the core SCF ► SCFMet30 disassembly is stress signal specific