Characterisation of the mammalian family of DCN-type NEDD8 E3 ligases

Keuss, M. J., Thomas, Y., Mcarthur, R., Wood, N. T., Knebel, A. and Kurz, T. (2016) Characterisation of the mammalian family of DCN-type NEDD8 E3 ligases. Journal of Cell Science, 129(7), pp. 1441-1454. (doi: 10.1242/jcs.181784) (PMID:26906416)

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Abstract

Cullin-RING ligases (CRL) are ubiquitin E3s that bind substrates through variable substrate-receptor proteins. CRLs are activated by attachment of the ubiquitin-like protein NEDD8 to the Cullin subunit and DCNs are NEDD8 E3 ligases that promote neddylation. Mammalian cells express five DCN-like proteins and little is known about their specific functions or interaction partners. We found that DCNLs form stable stoichiometric complexes with CAND1 and Cullins that can only be neddylated in the presence of substrate adaptor. These DCNL-CUL-CAND1 complexes may represent “reserve” CRLs that can be rapidly activated when needed. We further found that all DCNLs interact with most Cullin subtypes, but that they are likely responsible for the neddylation of different subpopulations of any given Cullin. This is consistent with the fact that the subcellular localization of DCNLs in tissue culture cells differs and that they show unique tissue specific expression patterns in mice. Thus, the specificity between DCNL-type NEDD8 E3 enzymes and their Cullin substrates is only apparent in well-defined physiological contexts and related to their subcellular distribution and restricted expression.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Kurz, Dr Thimo
Authors: Keuss, M. J., Thomas, Y., Mcarthur, R., Wood, N. T., Knebel, A., and Kurz, T.
College/School:College of Medical Veterinary and Life Sciences > School of Molecular Biosciences
Journal Name:Journal of Cell Science
Publisher:Company of Biologists
ISSN:0021-9533
ISSN (Online):1477-9137
Copyright Holders:Copyright © 2016 The Company of Biologists Ltd.
First Published:First published in Journal of Cell Science 2016(129):1441-1454
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher

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