OTULIN Restricts Met1-Linked Ubiquitination to Control Innate Immune Signaling

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

Standard

OTULIN Restricts Met1-Linked Ubiquitination to Control Innate Immune Signaling. / Fiil, Berthe Katrine; Damgaard, Rune Busk; Wagner, Sebastian Alexander; Keusekotten, Kirstin; Fritsch, Melanie; Bekker-Jensen, Simon; Mailand, Niels; Choudhary, Chuna Ram; Komander, David; Gyrd-Hansen, Mads.

In: Molecular Cell, Vol. 50, No. 6, 27.06.2013, p. 818-30.

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

Harvard

Fiil, BK, Damgaard, RB, Wagner, SA, Keusekotten, K, Fritsch, M, Bekker-Jensen, S, Mailand, N, Choudhary, CR, Komander, D & Gyrd-Hansen, M 2013, 'OTULIN Restricts Met1-Linked Ubiquitination to Control Innate Immune Signaling', Molecular Cell, vol. 50, no. 6, pp. 818-30. https://doi.org/10.1016/j.molcel.2013.06.004

APA

Fiil, B. K., Damgaard, R. B., Wagner, S. A., Keusekotten, K., Fritsch, M., Bekker-Jensen, S., Mailand, N., Choudhary, C. R., Komander, D., & Gyrd-Hansen, M. (2013). OTULIN Restricts Met1-Linked Ubiquitination to Control Innate Immune Signaling. Molecular Cell, 50(6), 818-30. https://doi.org/10.1016/j.molcel.2013.06.004

Vancouver

Fiil BK, Damgaard RB, Wagner SA, Keusekotten K, Fritsch M, Bekker-Jensen S et al. OTULIN Restricts Met1-Linked Ubiquitination to Control Innate Immune Signaling. Molecular Cell. 2013 Jun 27;50(6):818-30. https://doi.org/10.1016/j.molcel.2013.06.004

Author

Fiil, Berthe Katrine ; Damgaard, Rune Busk ; Wagner, Sebastian Alexander ; Keusekotten, Kirstin ; Fritsch, Melanie ; Bekker-Jensen, Simon ; Mailand, Niels ; Choudhary, Chuna Ram ; Komander, David ; Gyrd-Hansen, Mads. / OTULIN Restricts Met1-Linked Ubiquitination to Control Innate Immune Signaling. In: Molecular Cell. 2013 ; Vol. 50, No. 6. pp. 818-30.

Bibtex

@article{f78235eb1d834adeb97b21c8ca76b0b4,

title = "OTULIN Restricts Met1-Linked Ubiquitination to Control Innate Immune Signaling",

abstract = "Conjugation of Met1-linked polyubiquitin (Met1-Ub) by the linear ubiquitin chain assembly complex (LUBAC) is an important regulatory modification in innate immune signaling. So far, only few Met1-Ub substrates have been described, and the regulatory mechanisms have remained elusive. We recently identified that the ovarian tumor (OTU) family deubiquitinase OTULIN specifically disassembles Met1-Ub. Here, we report that OTULIN is critical for limiting Met1-Ub accumulation after nucleotide-oligomerization domain-containing protein 2 (NOD2) stimulation, and that OTULIN depletion augments signaling downstream of NOD2. Affinity purification of Met1-Ub followed by quantitative proteomics uncovered RIPK2 as the predominant NOD2-regulated substrate. Accordingly, Met1-Ub on RIPK2 was largely inhibited by overexpressing OTULIN and was increased by OTULIN depletion. Intriguingly, OTULIN-depleted cells spontaneously accumulated Met1-Ub on LUBAC components, and NOD2 or TNFR1 stimulation led to extensive Met1-Ub accumulation on receptor complex components. We propose that OTULIN restricts Met1-Ub formation after immune receptor stimulation to prevent unwarranted proinflammatory signaling.",

author = "Fiil, {Berthe Katrine} and Damgaard, {Rune Busk} and Wagner, {Sebastian Alexander} and Kirstin Keusekotten and Melanie Fritsch and Simon Bekker-Jensen and Niels Mailand and Choudhary, {Chuna Ram} and David Komander and Mads Gyrd-Hansen",

year = "2013",

month = jun,

day = "27",

doi = "10.1016/j.molcel.2013.06.004",

language = "English",

volume = "50",

pages = "818--30",

journal = "Molecular Cell",

issn = "1097-2765",

publisher = "Cell Press",

number = "6",

}

RIS

TY - JOUR

T1 - OTULIN Restricts Met1-Linked Ubiquitination to Control Innate Immune Signaling

AU - Fiil, Berthe Katrine

AU - Damgaard, Rune Busk

AU - Wagner, Sebastian Alexander

AU - Keusekotten, Kirstin

AU - Fritsch, Melanie

AU - Bekker-Jensen, Simon

AU - Mailand, Niels

AU - Choudhary, Chuna Ram

AU - Komander, David

AU - Gyrd-Hansen, Mads

PY - 2013/6/27

Y1 - 2013/6/27

N2 - Conjugation of Met1-linked polyubiquitin (Met1-Ub) by the linear ubiquitin chain assembly complex (LUBAC) is an important regulatory modification in innate immune signaling. So far, only few Met1-Ub substrates have been described, and the regulatory mechanisms have remained elusive. We recently identified that the ovarian tumor (OTU) family deubiquitinase OTULIN specifically disassembles Met1-Ub. Here, we report that OTULIN is critical for limiting Met1-Ub accumulation after nucleotide-oligomerization domain-containing protein 2 (NOD2) stimulation, and that OTULIN depletion augments signaling downstream of NOD2. Affinity purification of Met1-Ub followed by quantitative proteomics uncovered RIPK2 as the predominant NOD2-regulated substrate. Accordingly, Met1-Ub on RIPK2 was largely inhibited by overexpressing OTULIN and was increased by OTULIN depletion. Intriguingly, OTULIN-depleted cells spontaneously accumulated Met1-Ub on LUBAC components, and NOD2 or TNFR1 stimulation led to extensive Met1-Ub accumulation on receptor complex components. We propose that OTULIN restricts Met1-Ub formation after immune receptor stimulation to prevent unwarranted proinflammatory signaling.

AB - Conjugation of Met1-linked polyubiquitin (Met1-Ub) by the linear ubiquitin chain assembly complex (LUBAC) is an important regulatory modification in innate immune signaling. So far, only few Met1-Ub substrates have been described, and the regulatory mechanisms have remained elusive. We recently identified that the ovarian tumor (OTU) family deubiquitinase OTULIN specifically disassembles Met1-Ub. Here, we report that OTULIN is critical for limiting Met1-Ub accumulation after nucleotide-oligomerization domain-containing protein 2 (NOD2) stimulation, and that OTULIN depletion augments signaling downstream of NOD2. Affinity purification of Met1-Ub followed by quantitative proteomics uncovered RIPK2 as the predominant NOD2-regulated substrate. Accordingly, Met1-Ub on RIPK2 was largely inhibited by overexpressing OTULIN and was increased by OTULIN depletion. Intriguingly, OTULIN-depleted cells spontaneously accumulated Met1-Ub on LUBAC components, and NOD2 or TNFR1 stimulation led to extensive Met1-Ub accumulation on receptor complex components. We propose that OTULIN restricts Met1-Ub formation after immune receptor stimulation to prevent unwarranted proinflammatory signaling.

U2 - 10.1016/j.molcel.2013.06.004

DO - 10.1016/j.molcel.2013.06.004

M3 - Journal article

C2 - 23806334

VL - 50

SP - 818

EP - 830

JO - Molecular Cell

JF - Molecular Cell

SN - 1097-2765

IS - 6

ER -

ID: 47417166