The Ubiquitin Ligase XIAP Recruits LUBAC for NOD2 Signaling in Inflammation and Innate Immunity

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The Ubiquitin Ligase XIAP Recruits LUBAC for NOD2 Signaling in Inflammation and Innate Immunity. / Damgaard, Rune Busk; Nachbur, Ueli; Yabal, Monica; Wong, Wendy Wei-Lynn; Fiil, Berthe Katrine; Kastirr, Mischa; Rieser, Eva; Rickard, James Arthur; Bankovacki, Aleksandra; Peschel, Christian; Ruland, Juergen; Bekker-Jensen, Simon; Mailand, Niels; Kaufmann, Thomas; Strasser, Andreas; Walczak, Henning; Silke, John; Jost, Philipp J; Gyrd-Hansen, Mads.

In: Molecular Cell, Vol. 46, No. 6, 2012, p. 746-58.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Damgaard, RB, Nachbur, U, Yabal, M, Wong, WW-L, Fiil, BK, Kastirr, M, Rieser, E, Rickard, JA, Bankovacki, A, Peschel, C, Ruland, J, Bekker-Jensen, S, Mailand, N, Kaufmann, T, Strasser, A, Walczak, H, Silke, J, Jost, PJ & Gyrd-Hansen, M 2012, 'The Ubiquitin Ligase XIAP Recruits LUBAC for NOD2 Signaling in Inflammation and Innate Immunity', Molecular Cell, vol. 46, no. 6, pp. 746-58. https://doi.org/10.1016/j.molcel.2012.04.014

APA

Damgaard, R. B., Nachbur, U., Yabal, M., Wong, W. W-L., Fiil, B. K., Kastirr, M., Rieser, E., Rickard, J. A., Bankovacki, A., Peschel, C., Ruland, J., Bekker-Jensen, S., Mailand, N., Kaufmann, T., Strasser, A., Walczak, H., Silke, J., Jost, P. J., & Gyrd-Hansen, M. (2012). The Ubiquitin Ligase XIAP Recruits LUBAC for NOD2 Signaling in Inflammation and Innate Immunity. Molecular Cell, 46(6), 746-58. https://doi.org/10.1016/j.molcel.2012.04.014

Vancouver

Damgaard RB, Nachbur U, Yabal M, Wong WW-L, Fiil BK, Kastirr M et al. The Ubiquitin Ligase XIAP Recruits LUBAC for NOD2 Signaling in Inflammation and Innate Immunity. Molecular Cell. 2012;46(6):746-58. https://doi.org/10.1016/j.molcel.2012.04.014

Author

Damgaard, Rune Busk ; Nachbur, Ueli ; Yabal, Monica ; Wong, Wendy Wei-Lynn ; Fiil, Berthe Katrine ; Kastirr, Mischa ; Rieser, Eva ; Rickard, James Arthur ; Bankovacki, Aleksandra ; Peschel, Christian ; Ruland, Juergen ; Bekker-Jensen, Simon ; Mailand, Niels ; Kaufmann, Thomas ; Strasser, Andreas ; Walczak, Henning ; Silke, John ; Jost, Philipp J ; Gyrd-Hansen, Mads. / The Ubiquitin Ligase XIAP Recruits LUBAC for NOD2 Signaling in Inflammation and Innate Immunity. In: Molecular Cell. 2012 ; Vol. 46, No. 6. pp. 746-58.

Bibtex

@article{fbb72e8809f04662b6d74ba9e5b4b8c7,
title = "The Ubiquitin Ligase XIAP Recruits LUBAC for NOD2 Signaling in Inflammation and Innate Immunity",
abstract = "Nucleotide-binding and oligomerization domain (NOD)-like receptors constitute a first line of defense against invading bacteria. X-linked Inhibitor of Apoptosis (XIAP) is implicated in the control of bacterial infections, and mutations in XIAP are causally linked to immunodeficiency in X-linked lymphoproliferative syndrome type-2 (XLP-2). Here, we demonstrate that the RING domain of XIAP is essential for NOD2 signaling and that XIAP contributes to exacerbation of inflammation-induced hepatitis in experimental mice. We find that XIAP ubiquitylates RIPK2 and recruits the linear ubiquitin chain assembly complex (LUBAC) to NOD2. We further show that LUBAC activity is required for efficient NF-¿B activation and secretion of proinflammatory cytokines after NOD2 stimulation. Remarkably, XLP-2-derived XIAP variants have impaired ubiquitin ligase activity, fail to ubiquitylate RIPK2, and cannot facilitate NOD2 signaling. We conclude that XIAP and LUBAC constitute essential ubiquitin ligases in NOD2-mediated inflammatory signaling and propose that deregulation of NOD2 signaling contributes to XLP-2 pathogenesis.",
author = "Damgaard, {Rune Busk} and Ueli Nachbur and Monica Yabal and Wong, {Wendy Wei-Lynn} and Fiil, {Berthe Katrine} and Mischa Kastirr and Eva Rieser and Rickard, {James Arthur} and Aleksandra Bankovacki and Christian Peschel and Juergen Ruland and Simon Bekker-Jensen and Niels Mailand and Thomas Kaufmann and Andreas Strasser and Henning Walczak and John Silke and Jost, {Philipp J} and Mads Gyrd-Hansen",
note = "Copyright {\textcopyright} 2012 Elsevier Inc. All rights reserved.",
year = "2012",
doi = "10.1016/j.molcel.2012.04.014",
language = "English",
volume = "46",
pages = "746--58",
journal = "Molecular Cell",
issn = "1097-2765",
publisher = "Cell Press",
number = "6",

}

RIS

TY - JOUR

T1 - The Ubiquitin Ligase XIAP Recruits LUBAC for NOD2 Signaling in Inflammation and Innate Immunity

AU - Damgaard, Rune Busk

AU - Nachbur, Ueli

AU - Yabal, Monica

AU - Wong, Wendy Wei-Lynn

AU - Fiil, Berthe Katrine

AU - Kastirr, Mischa

AU - Rieser, Eva

AU - Rickard, James Arthur

AU - Bankovacki, Aleksandra

AU - Peschel, Christian

AU - Ruland, Juergen

AU - Bekker-Jensen, Simon

AU - Mailand, Niels

AU - Kaufmann, Thomas

AU - Strasser, Andreas

AU - Walczak, Henning

AU - Silke, John

AU - Jost, Philipp J

AU - Gyrd-Hansen, Mads

N1 - Copyright © 2012 Elsevier Inc. All rights reserved.

PY - 2012

Y1 - 2012

N2 - Nucleotide-binding and oligomerization domain (NOD)-like receptors constitute a first line of defense against invading bacteria. X-linked Inhibitor of Apoptosis (XIAP) is implicated in the control of bacterial infections, and mutations in XIAP are causally linked to immunodeficiency in X-linked lymphoproliferative syndrome type-2 (XLP-2). Here, we demonstrate that the RING domain of XIAP is essential for NOD2 signaling and that XIAP contributes to exacerbation of inflammation-induced hepatitis in experimental mice. We find that XIAP ubiquitylates RIPK2 and recruits the linear ubiquitin chain assembly complex (LUBAC) to NOD2. We further show that LUBAC activity is required for efficient NF-¿B activation and secretion of proinflammatory cytokines after NOD2 stimulation. Remarkably, XLP-2-derived XIAP variants have impaired ubiquitin ligase activity, fail to ubiquitylate RIPK2, and cannot facilitate NOD2 signaling. We conclude that XIAP and LUBAC constitute essential ubiquitin ligases in NOD2-mediated inflammatory signaling and propose that deregulation of NOD2 signaling contributes to XLP-2 pathogenesis.

AB - Nucleotide-binding and oligomerization domain (NOD)-like receptors constitute a first line of defense against invading bacteria. X-linked Inhibitor of Apoptosis (XIAP) is implicated in the control of bacterial infections, and mutations in XIAP are causally linked to immunodeficiency in X-linked lymphoproliferative syndrome type-2 (XLP-2). Here, we demonstrate that the RING domain of XIAP is essential for NOD2 signaling and that XIAP contributes to exacerbation of inflammation-induced hepatitis in experimental mice. We find that XIAP ubiquitylates RIPK2 and recruits the linear ubiquitin chain assembly complex (LUBAC) to NOD2. We further show that LUBAC activity is required for efficient NF-¿B activation and secretion of proinflammatory cytokines after NOD2 stimulation. Remarkably, XLP-2-derived XIAP variants have impaired ubiquitin ligase activity, fail to ubiquitylate RIPK2, and cannot facilitate NOD2 signaling. We conclude that XIAP and LUBAC constitute essential ubiquitin ligases in NOD2-mediated inflammatory signaling and propose that deregulation of NOD2 signaling contributes to XLP-2 pathogenesis.

U2 - 10.1016/j.molcel.2012.04.014

DO - 10.1016/j.molcel.2012.04.014

M3 - Journal article

C2 - 22607974

VL - 46

SP - 746

EP - 758

JO - Molecular Cell

JF - Molecular Cell

SN - 1097-2765

IS - 6

ER -

ID: 40289691