title: CSN- and CAND1-dependent remodelling of the budding yeast SCF complex.
abstract: Cullin-RING ligases (CRLs) are ubiquitin E3 enzymes with variable substrate-adaptor and -receptor subunits. All CRLs are activated by modification of the cullin subunit with the ubiquitin-like protein Nedd8 (neddylation). The protein CAND1 (Cullin-associated-Nedd8-dissociated-1) also promotes CRL activity, even though it only interacts with inactive ligase complexes. The molecular mechanism underlying this behaviour remains largely unclear. Here, we find that yeast SCF (Skp1-Cdc53-F-box) Cullin-RING complexes are remodelled in a CAND1-dependent manner, when cells are switched from growth in fermentable to non-fermentable carbon sources. Mechanistically, CAND1 promotes substrate adaptor release following SCF deneddylation by the COP9 signalosome (CSN). CSN- or CAND1-mutant cells fail to release substrate adaptors. This delays the formation of new complexes during SCF reactivation and results in substrate degradation defects. Our results shed light on how CAND1 regulates CRL activity and demonstrate that the cullin neddylation-deneddylation cycle is not only required to activate CRLs, but also to regulate substrate specificity through dynamic substrate adaptor exchange.
authors.affiliation: Scottish Institute for Cell Signalling, Protein Ubiquitylation Unit, College of Life Sciences, University of Dundee, Dundee, Scotland, UK.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Zemla
authors.forename: Yann
authors.initials: Y
authors.lastname: Thomas
authors.forename: Sylwia
authors.initials: S
authors.lastname: Kedziora
authors.forename: Axel
authors.initials: A
authors.lastname: Knebel
authors.forename: Nicola T
authors.initials: NT
authors.lastname: Wood
authors.forename: Gwenaël
authors.initials: G
authors.lastname: Rabut
authors.forename: Thimo
authors.initials: T
authors.lastname: Kurz
mesh_terms: D002244:Carbon / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000502:physiology*
chemical_list: D029701:Saccharomyces cerevisiae Proteins; D002244:Carbon
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