title: Signal-induced disassembly of the SCF ubiquitin ligase complex by Cdc48/p97.
abstract: 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.
authors.affiliation: Department of Biological Chemistry, College of Medicine, University of California, Irvine, CA 92697-1700, USA.
authors.forename: James L
authors.initials: JL
authors.lastname: Yen
authors.forename: Karin
authors.initials: K
authors.lastname: Flick
authors.forename: Christie V
authors.initials: CV
authors.lastname: Papagiannis
authors.forename: Radhika
authors.initials: R
authors.lastname: Mathur
authors.forename: An
authors.initials: A
authors.lastname: Tyrrell
authors.forename: Ikram
authors.initials: I
authors.lastname: Ouni
authors.forename: Robyn M
authors.initials: RM
authors.lastname: Kaake
authors.forename: Lan
authors.initials: L
authors.lastname: Huang
authors.forename: Peter
authors.initials: P
authors.lastname: Kaiser
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D002104:Cadmium / Q000494:pharmacology; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D044783:F-Box Proteins / Q000235:genetics / Q000378:metabolism; D006868:Hydrolysis / Q000187:drug effects; D046912:Multiprotein Complexes / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D044843:SKP Cullin F-Box Protein Ligases / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000201:enzymology*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D015398:Signal Transduction; D013379:Substrate Specificity; D054875:Ubiquitination; D000074405:Valosin Containing Protein
chemical_list: D018797:Cell Cycle Proteins; D044783:F-Box Proteins; D046912:Multiprotein Complexes; D029701:Saccharomyces cerevisiae Proteins; D002104:Cadmium; D000255:Adenosine Triphosphate; D044843:SKP Cullin F-Box Protein Ligases; C120507:SKP1 protein, S cerevisiae; D000251:Adenosine Triphosphatases; C000614177:CDC48 protein, S cerevisiae; D000074405:Valosin Containing Protein