Lys63/Met1-hybrid ubiquitin chains are commonly formed during the activation of innate immune signalling.

Christoph Emmerich; Siddharth Bakshi; Ian Kelsall; Juan Ortiz-Guerrero; Natalia Shpiro; Philip Cohen

doi:10.1016/j.bbrc.2016.04.141

Lys63/Met1-hybrid ubiquitin chains are commonly formed during the activation of innate immune signalling.

Christoph Emmerich, Siddharth Bakshi, Ian Kelsall, Juan Ortiz-Guerrero, Natalia Shpiro, Philip Cohen (Lead / Corresponding author)

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Abstract

We have reported previously that activation of the MyD88-signaling network rapidly induces the formation of hybrid ubiquitin chains containing both Lys63-linked and Met1-linked ubiquitin (Ub) oligomers, some of which are attached covalently to Interleukin Receptor Associated kinase 1. Here we show that Lys63/Met1-Ub hybrids are also formed rapidly when the TNFα, TLR3/TRIF- and NOD1/RIP2-signaling networks are activated, some of which are attached covalently to Receptor-Interacting Protein 1 (TNFα pathway) or Receptor-Interacting Protein 2 (NOD1 pathway). These observations suggest that the formation of Lys63/Met1-Ub hybrids are of general significance for the regulation of innate immune signaling systems, and their potential roles in vivo are discussed. We also report that TNFα induces the attachment of Met1-linked Ub chains directly to TNF receptor 1, which do not seem to be attached covalently to Lys63-linked or other types of ubiquitin chain.

Original language	English
Pages (from-to)	452-461
Number of pages	10
Journal	Biochemical and Biophysical Research Communications
Volume	474
Issue number	3
Early online date	28 Apr 2016
DOIs	https://doi.org/10.1016/j.bbrc.2016.04.141
Publication status	Published - 3 Jun 2016

Keywords

Ubiquitin
innate
immunity
TNF
TLR3
NOD1
LUBAC

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10.1016/j.bbrc.2016.04.141Licence: CC BY

Final Published Version
© 2016 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Final published version, 2.47 MBLicence: CC BY

Cite this

@article{82cd1cccfa0d42cdbd21141ecd2ab305,

title = "Lys63/Met1-hybrid ubiquitin chains are commonly formed during the activation of innate immune signalling.",

abstract = "We have reported previously that activation of the MyD88-signaling network rapidly induces the formation of hybrid ubiquitin chains containing both Lys63-linked and Met1-linked ubiquitin (Ub) oligomers, some of which are attached covalently to Interleukin Receptor Associated kinase 1. Here we show that Lys63/Met1-Ub hybrids are also formed rapidly when the TNFα, TLR3/TRIF- and NOD1/RIP2-signaling networks are activated, some of which are attached covalently to Receptor-Interacting Protein 1 (TNFα pathway) or Receptor-Interacting Protein 2 (NOD1 pathway). These observations suggest that the formation of Lys63/Met1-Ub hybrids are of general significance for the regulation of innate immune signaling systems, and their potential roles in vivo are discussed. We also report that TNFα induces the attachment of Met1-linked Ub chains directly to TNF receptor 1, which do not seem to be attached covalently to Lys63-linked or other types of ubiquitin chain.",

keywords = "Ubiquitin, innate, immunity, TNF, TLR3, NOD1, LUBAC",

author = "Christoph Emmerich and Siddharth Bakshi and Ian Kelsall and Juan Ortiz-Guerrero and Natalia Shpiro and Philip Cohen",

note = "This work was supported by the Wellcome Trust [grant WT100294] and by AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Janssen Pharmaceutica and Merck-Serono.",

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doi = "10.1016/j.bbrc.2016.04.141",

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T1 - Lys63/Met1-hybrid ubiquitin chains are commonly formed during the activation of innate immune signalling.

AU - Emmerich, Christoph

AU - Bakshi, Siddharth

AU - Kelsall, Ian

AU - Ortiz-Guerrero, Juan

AU - Shpiro, Natalia

AU - Cohen, Philip

N1 - This work was supported by the Wellcome Trust [grant WT100294] and by AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Janssen Pharmaceutica and Merck-Serono.

PY - 2016/6/3

Y1 - 2016/6/3

N2 - We have reported previously that activation of the MyD88-signaling network rapidly induces the formation of hybrid ubiquitin chains containing both Lys63-linked and Met1-linked ubiquitin (Ub) oligomers, some of which are attached covalently to Interleukin Receptor Associated kinase 1. Here we show that Lys63/Met1-Ub hybrids are also formed rapidly when the TNFα, TLR3/TRIF- and NOD1/RIP2-signaling networks are activated, some of which are attached covalently to Receptor-Interacting Protein 1 (TNFα pathway) or Receptor-Interacting Protein 2 (NOD1 pathway). These observations suggest that the formation of Lys63/Met1-Ub hybrids are of general significance for the regulation of innate immune signaling systems, and their potential roles in vivo are discussed. We also report that TNFα induces the attachment of Met1-linked Ub chains directly to TNF receptor 1, which do not seem to be attached covalently to Lys63-linked or other types of ubiquitin chain.

AB - We have reported previously that activation of the MyD88-signaling network rapidly induces the formation of hybrid ubiquitin chains containing both Lys63-linked and Met1-linked ubiquitin (Ub) oligomers, some of which are attached covalently to Interleukin Receptor Associated kinase 1. Here we show that Lys63/Met1-Ub hybrids are also formed rapidly when the TNFα, TLR3/TRIF- and NOD1/RIP2-signaling networks are activated, some of which are attached covalently to Receptor-Interacting Protein 1 (TNFα pathway) or Receptor-Interacting Protein 2 (NOD1 pathway). These observations suggest that the formation of Lys63/Met1-Ub hybrids are of general significance for the regulation of innate immune signaling systems, and their potential roles in vivo are discussed. We also report that TNFα induces the attachment of Met1-linked Ub chains directly to TNF receptor 1, which do not seem to be attached covalently to Lys63-linked or other types of ubiquitin chain.

KW - Ubiquitin

KW - innate

KW - immunity

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KW - TLR3

KW - NOD1

KW - LUBAC

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JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

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ER -

Lys63/Met1-hybrid ubiquitin chains are commonly formed during the activation of innate immune signalling.

Abstract

Keywords

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Characterisation of Signal Transduction Pathways that Restrict Activation of the Innate Immune System to Prevent Inflammatory and Autoimmune Diseases (Programme Grant)

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Lys63/Met1-hybrid ubiquitin chains are commonly formed during the activation of innate immune signalling.

Abstract

Keywords

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Characterisation of Signal Transduction Pathways that Restrict Activation of the Innate Immune System to Prevent Inflammatory and Autoimmune Diseases (Programme Grant)

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