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

Thomas, Y., Scott, D. C., Kristariyanto, Y. A., Rinehart, J., Clark, K., Cohen, P. and Kurz, T. (2018) The NEDD8 E3 ligase DCNL5 is phosphorylated by IKK alpha during Toll-like receptor activation. PLoS ONE, 13(6), e0199197. (doi: 10.1371/journal.pone.0199197) (PMID:29958295) (PMCID:PMC6025869)

[img]
Preview
Text
164126.pdf - Published Version
Available under License Creative Commons Public Domain Dedication.

6MB

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.

Item Type:Articles
Additional Information:This work was supported by the Medical Research Council (MC_UU_12016/7), an ERC Starting Investigator Grant (to TK), as well as the pharmaceutical companies supporting the Division of Signal Transduction Therapy Unit (AstraZeneca, Boehringer-Ingelheim, GlaxoSmithKline, Merck, Janssen Pharmaceutica and Pfizer).
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Kurz, Dr Thimo
Creator Roles:
Kurz, T.Supervision, Writing – original draft, Writing – review and editing
Authors: Thomas, Y., Scott, D. C., Kristariyanto, Y. A., Rinehart, J., Clark, K., Cohen, P., and Kurz, T.
College/School:College of Medical Veterinary and Life Sciences > School of Molecular Biosciences
Journal Name:PLoS ONE
Publisher:Public Library of Science
ISSN:1932-6203
ISSN (Online):1932-6203
Copyright Holders:This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose​.
First Published:First published in PLoS ONE 13(6):e0199197
Publisher Policy:Reproduced under a Creative Commons CC0 public domain dedication

University Staff: Request a correction | Enlighten Editors: Update this record