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

• Published in: PloS one Vol. 13; no. 6; p. e0199197
• Main Authors: Thomas, Yann, Scott, Daniel C, Kristariyanto, Yosua Adi, Rinehart, Jesse, Clark, Kristopher, Cohen, Philip, Kurz, Thimo
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 29.06.2018; Public Library of Science (PLoS)
• Subjects: Activation; Animals; Biology; Biology and Life Sciences; Cancer; Cell cycle; Councils; Cullin; Cytokines; Enzymes; Health aspects; HEK293 Cells; Humans; I-kappa B Kinase - genetics; I-kappa B Kinase - immunology; IKK protein; Immune system; Immunity; Immunity, Innate; Immunoglobulins; Immunologic research; Innate immunity; Kinases; Life sciences; Localization; Medical research; Medicine and Health Sciences; Mice; Natural immunity; NEDD8 Protein - genetics; NEDD8 Protein - immunology; Oncogene Proteins - genetics; Oncogene Proteins - immunology; Peptide Synthases - genetics; Peptide Synthases - immunology; Phosphorylation; Phosphorylation - genetics; Phosphorylation - immunology; Physical Sciences; Physiological aspects; Post-translation; Post-translational modifications; Proteins; RAW 264.7 Cells; Receptor mechanisms; Receptors; Research and Analysis Methods; Serine; Sheep; Signal transduction; Signal Transduction - genetics; Signal Transduction - immunology; Signaling; Substrates; Toll-like receptors; Ubiquitin; Ubiquitin-protein ligase; United Kingdom > UK; United States > US; Connecticut
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0199197

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.