CSN- and CAND1-dependent remodelling of the budding yeast SCF complex

Zemla, A., Thomas, Y., Kedziora, S., Knebel, A., Wood, N. T., Rabut, G. and Kurz, T. (2013) CSN- and CAND1-dependent remodelling of the budding yeast SCF complex. Nature Communications, 4, 1641. (doi: 10.1038/ncomms2628) (PMID:23535662)

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.

• Item Type: Articles
• Additional Information: This work was supported by an ERC Starting Investigator Grant to T.K., by a European Regional Development Fund Grant for an Innovation Pipeline for Translational Science (grant number LUPS/ERDF/2008/2/1/ 0429), by a grant from the Scottish Government to the Scottish Institute for Cell Signalling and by the pharmaceutical companies supporting the Division of Signal Transduction Therapy Unit (AstraZeneca, Boehringer-Ingelheim, GlaxoSmithKline, Merck KGaA, Janssen Pharmaceutica and Pfizer).
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Kurz, Dr Thimo
• Authors: Zemla, A., Thomas, Y., Kedziora, S., Knebel, A., Wood, N. T., Rabut, G., and Kurz, T.
• College/School: College of Medical Veterinary and Life Sciences > School of Molecular Biosciences
• Journal Name: Nature Communications
• Publisher: Nature Publishing Group
• ISSN: 2041-1723
• ISSN (Online): 2041-1723
• Published Online: 27 March 2013
• Copyright Holders: Copyright © 2013 Macmillan Publishers Limited
• First Published: First published in Nature Communications 4: 1641
• Publisher Policy: Reproduced under a Creative Commons License