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)
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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 |
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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: | |
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 |
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