The NEDD8 E3 ligase DCNL5 is phosphorylated by IKK alpha during Toll-like receptor activation

PLoS One. 2018 Jun 29;13(6):e0199197. doi: 10.1371/journal.pone.0199197. eCollection 2018.

Abstract

The activity of Cullin-RING ubiquitin E3 ligases (CRL) is regulated by NEDD8 modification. DCN-like proteins promote Cullin neddylation as scaffold-like E3s. One DCNL, DCNL5, is highly expressed in immune tissue. Here, we provide evidence that DCNL5 may be involved in innate immunity, as it is a direct substrate of the kinase IKKα during immune signalling. We find that upon activation of Toll-like receptors, DCNL5 gets rapidly and transiently phosphorylated on a specific N-terminal serine residue (S41). This phosphorylation event is specifically mediated by IKKα and not IKKβ. Our data for the first time provides evidence that DCNL proteins are post-translationally modified in an inducible manner. Our findings also provide the first example of a DCNL member as a kinase substrate in a signalling pathway, indicating that the activity of at least some DCNLs may be regulated.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • HEK293 Cells
  • Humans
  • I-kappa B Kinase / genetics
  • I-kappa B Kinase / immunology*
  • Immunity, Innate*
  • Mice
  • NEDD8 Protein / genetics
  • NEDD8 Protein / immunology
  • Oncogene Proteins / genetics
  • Oncogene Proteins / immunology*
  • Peptide Synthases / genetics
  • Peptide Synthases / immunology*
  • Phosphorylation / genetics
  • Phosphorylation / immunology
  • RAW 264.7 Cells
  • Signal Transduction / genetics
  • Signal Transduction / immunology*

Substances

  • NEDD8 Protein
  • NEDD8 protein, human
  • Nedd8 protein, mouse
  • Oncogene Proteins
  • Chuk protein, mouse
  • I-kappa B Kinase
  • DCUN1D5 protein, human
  • Peptide Synthases