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

Matthew J Keuss1, Yann Thomas1, Robin Mcarthur1

  • 1Medical Research Council Protein Phosphorylation and Ubiquitylation Unit, College of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.

Journal of Cell Science
|February 25, 2016
PubMed

Insights

DCNL proteins regulate cullin-RING ligase (CRL) activity by promoting neddylation. These DCNL complexes form a reserve pool of CRLs, with specificity determined by cellular localization and expression patterns.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • Cullin-RING ligases (CRLs) are crucial ubiquitin E3 enzymes.
  • CRLs require NEDD8 attachment to the cullin subunit for activation.
  • DCNLs are NEDD8 E3 ligases that facilitate neddylation.

Purpose of the Study:

  • To investigate the specific functions and interaction partners of mammalian DCNL proteins.
  • To understand the regulation and specificity of DCNL-mediated neddylation.

Main Methods:

  • Analysis of DCNL protein complexes with CAND1 and cullins.
  • Investigation of neddylation in the presence of substrate adaptors.
  • Assessment of DCNL interactions with various cullin subtypes.
  • Examination of DCNL subcellular localization and tissue-specific expression in mice.

Main Results:

  • DCNLs form stable complexes with CAND1 and cullins, requiring substrate adaptors for neddylation.
  • These complexes may act as a reserve pool of CRLs for rapid activation.
  • All DCNLs interact with most cullin subtypes, suggesting distinct roles.
  • DCNLs exhibit differential subcellular localization and unique tissue-specific expression patterns.

Conclusions:

  • DCNL specificity towards cullin substrates is context-dependent, influenced by subcellular distribution and expression.
  • DCNL-type NEDD8 E3 ligases play a critical role in regulating CRL activity.
  • Understanding DCNL function provides insights into CRL pathway regulation.
Keywords:
CRLCullin-RING ligasesDCUN1DNEDD8SCCROUbiquitin

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