Signal-induced disassembly of the SCF ubiquitin ligase complex by Cdc48/p97.

James L Yen, Karin Flick, Christie V Papagiannis, Radhika Mathur, An Tyrrell, Ikram Ouni, Robyn M Kaake, Lan Huang, Peter Kaiser

Molecular cell 2012 Oct 26

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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 SCF(Met30) 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. Copyright © 2012 Elsevier Inc. All rights reserved.

Citation

James L Yen, Karin Flick, Christie V Papagiannis, Radhika Mathur, An Tyrrell, Ikram Ouni, Robyn M Kaake, Lan Huang, Peter Kaiser. Signal-induced disassembly of the SCF ubiquitin ligase complex by Cdc48/p97. Molecular cell. 2012 Oct 26;48(2):288-97