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

Yann Thomas, Daniel C Scott, Yosua Adi Kristariyanto, Jesse Rinehart, Kristopher Clark, Philip Cohen, Thimo Kurz (Lead / Corresponding author)

Research output: Contribution to journalArticle

1 Citation (Scopus)
75 Downloads (Pure)

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.

Original languageEnglish
Article numbere0199197
Pages (from-to)1-19
Number of pages19
JournalPLoS ONE
Volume13
Issue number6
DOIs
Publication statusPublished - 29 Jun 2018

Fingerprint

IKappaB kinase
I-kappa B Kinase
Cullin Proteins
Ubiquitin-Protein Ligases
Toll-Like Receptors
ligases
Phosphotransferases
Chemical activation
Phosphorylation
phosphotransferases (kinases)
Substrates
Innate Immunity
Scaffolds
Serine
ubiquitin-protein ligase
Tissue
serine
phosphorylation
proteins
Proteins

Cite this

Thomas, Y., Scott, D. C., Kristariyanto, Y. A., Rinehart, J., Clark, K., Cohen, P., & Kurz, T. (2018). The NEDD8 E3 ligase DCNL5 is phosphorylated by IKK alpha during Toll-like receptor activation. PLoS ONE, 13(6), 1-19. [e0199197]. https://doi.org/10.1371/journal.pone.0199197
Thomas, Yann ; Scott, Daniel C ; Kristariyanto, Yosua Adi ; Rinehart, Jesse ; Clark, Kristopher ; Cohen, Philip ; Kurz, Thimo. / The NEDD8 E3 ligase DCNL5 is phosphorylated by IKK alpha during Toll-like receptor activation. In: PLoS ONE. 2018 ; Vol. 13, No. 6. pp. 1-19.
@article{c42c1f1888f14a50a3516792f5abaaec,
title = "The NEDD8 E3 ligase DCNL5 is phosphorylated by IKK alpha during Toll-like receptor activation",
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.",
author = "Yann Thomas and Scott, {Daniel C} and Kristariyanto, {Yosua Adi} and Jesse Rinehart and Kristopher Clark and Philip Cohen and Thimo Kurz",
note = "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). We have the following interests. This study was partly supported by the pharmaceutical companies supporting the Division of Signal Transduction Therapy Unit (AstraZeneca, Boehringer-Ingelheim, GlaxoSmithKline, Merck, Janssen Pharmaceutica and Pfizer). There are no patents, products in development or marketed products to declare.",
year = "2018",
month = "6",
day = "29",
doi = "10.1371/journal.pone.0199197",
language = "English",
volume = "13",
pages = "1--19",
journal = "PLoS ONE",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "6",

}

Thomas, Y, Scott, DC, Kristariyanto, YA, Rinehart, J, Clark, K, Cohen, P & Kurz, T 2018, 'The NEDD8 E3 ligase DCNL5 is phosphorylated by IKK alpha during Toll-like receptor activation', PLoS ONE, vol. 13, no. 6, e0199197, pp. 1-19. https://doi.org/10.1371/journal.pone.0199197

The NEDD8 E3 ligase DCNL5 is phosphorylated by IKK alpha during Toll-like receptor activation. / Thomas, Yann; Scott, Daniel C; Kristariyanto, Yosua Adi; Rinehart, Jesse; Clark, Kristopher; Cohen, Philip; Kurz, Thimo (Lead / Corresponding author).

In: PLoS ONE, Vol. 13, No. 6, e0199197, 29.06.2018, p. 1-19.

Research output: Contribution to journalArticle

TY - JOUR

T1 - The NEDD8 E3 ligase DCNL5 is phosphorylated by IKK alpha during Toll-like receptor activation

AU - Thomas, Yann

AU - Scott, Daniel C

AU - Kristariyanto, Yosua Adi

AU - Rinehart, Jesse

AU - Clark, Kristopher

AU - Cohen, Philip

AU - Kurz, Thimo

N1 - 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). We have the following interests. This study was partly supported by the pharmaceutical companies supporting the Division of Signal Transduction Therapy Unit (AstraZeneca, Boehringer-Ingelheim, GlaxoSmithKline, Merck, Janssen Pharmaceutica and Pfizer). There are no patents, products in development or marketed products to declare.

PY - 2018/6/29

Y1 - 2018/6/29

N2 - 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.

AB - 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.

U2 - 10.1371/journal.pone.0199197

DO - 10.1371/journal.pone.0199197

M3 - Article

C2 - 29958295

VL - 13

SP - 1

EP - 19

JO - PLoS ONE

JF - PLoS ONE

SN - 1932-6203

IS - 6

M1 - e0199197

ER -

Thomas Y, Scott DC, Kristariyanto YA, Rinehart J, Clark K, Cohen P et al. The NEDD8 E3 ligase DCNL5 is phosphorylated by IKK alpha during Toll-like receptor activation. PLoS ONE. 2018 Jun 29;13(6):1-19. e0199197. https://doi.org/10.1371/journal.pone.0199197