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

Matthew J Keuss, Yann Thomas, Robin Mcarthur, Nicola T Wood, Axel Knebel, Thimo Kurz (Lead / Corresponding author)

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Abstract

Cullin-RING ligases (CRL) are ubiquitin E3 enzymes that bind substrates through variable substrate receptor proteins and are activated by attachment of the ubiquitin-like protein NEDD8 to the cullin subunit. DCNs are NEDD8 E3 ligases that promote neddylation. Mammalian cells express five DCN-like (DCNL) proteins but 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 a substrate adaptor. These CAND-cullin-DCNL complexes might 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 probably 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 inmice. 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.

Original languageEnglish
Pages (from-to)1441-1454
Number of pages14
JournalJournal of Cell Science
Volume129
Issue number7
Early online date18 Feb 2016
DOIs
Publication statusPublished - 1 Apr 2016

Keywords

  • CRL
  • Cullin-RING ligases
  • DCUN1D
  • NEDD8
  • SCCRO
  • Ubiquitin

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