Molecular basis and regulation of OTULIN-LUBAC interaction

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Molecular basis and regulation of OTULIN-LUBAC interaction. / Elliott, Paul R.; Al-Saoudi, Sofie Vincents; Marco-Casanova, Paola; Fiil, Berthe Katrine; Keusekotten, Kirstin; Mailand, Niels; Freund, Stefan M. V.; Gyrd-Hansen, Mads; Komander, David.

In: Molecular Cell, Vol. 54, No. 3, 2014, p. 335-348.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Elliott, PR, Al-Saoudi, SV, Marco-Casanova, P, Fiil, BK, Keusekotten, K, Mailand, N, Freund, SMV, Gyrd-Hansen, M & Komander, D 2014, 'Molecular basis and regulation of OTULIN-LUBAC interaction', Molecular Cell, vol. 54, no. 3, pp. 335-348. https://doi.org/10.1016/j.molcel.2014.03.018

APA

Elliott, P. R., Al-Saoudi, S. V., Marco-Casanova, P., Fiil, B. K., Keusekotten, K., Mailand, N., ... Komander, D. (2014). Molecular basis and regulation of OTULIN-LUBAC interaction. Molecular Cell, 54(3), 335-348. https://doi.org/10.1016/j.molcel.2014.03.018

Vancouver

Elliott PR, Al-Saoudi SV, Marco-Casanova P, Fiil BK, Keusekotten K, Mailand N et al. Molecular basis and regulation of OTULIN-LUBAC interaction. Molecular Cell. 2014;54(3):335-348. https://doi.org/10.1016/j.molcel.2014.03.018

Author

Elliott, Paul R. ; Al-Saoudi, Sofie Vincents ; Marco-Casanova, Paola ; Fiil, Berthe Katrine ; Keusekotten, Kirstin ; Mailand, Niels ; Freund, Stefan M. V. ; Gyrd-Hansen, Mads ; Komander, David. / Molecular basis and regulation of OTULIN-LUBAC interaction. In: Molecular Cell. 2014 ; Vol. 54, No. 3. pp. 335-348.

Bibtex

@article{f34de31ac4f84dcd8c371c34ce4a83c5,
title = "Molecular basis and regulation of OTULIN-LUBAC interaction",
abstract = "The linear ubiquitin (Ub) chain assembly complex (LUBAC) generates Met1-linked {"}linear{"} Ub chains that regulate the activation of the nuclear factor κB (NFκB) transcription factor and other processes. We recently discovered OTULIN as a deubiquitinase that specifically cleaves Met1-linked polyUb. Now, we show that OTULIN binds via a conserved PUB-interacting motif (PIM) to the PUB domain of the LUBAC component HOIP. Crystal structures and nuclear magnetic resonance experiments reveal the molecular basis for the high-affinity interaction and explain why OTULIN binds the HOIP PUB domain specifically. Analysis of LUBAC-induced NFκB signaling suggests that OTULIN needs to be present on LUBAC in order to restrict Met1-polyUb signaling. Moreover, LUBAC-OTULIN complex formation is regulated by OTULIN phosphorylation in the PIM. Phosphorylation of OTULIN prevents HOIP binding, whereas unphosphorylated OTULIN is part of the endogenous LUBAC complex. Our work exemplifies how coordination of ubiquitin assembly and disassembly activities in protein complexes regulates individual Ub linkage types.",
author = "Elliott, {Paul R.} and Al-Saoudi, {Sofie Vincents} and Paola Marco-Casanova and Fiil, {Berthe Katrine} and Kirstin Keusekotten and Niels Mailand and Freund, {Stefan M. V.} and Mads Gyrd-Hansen and David Komander",
note = "Copyright {\circledC} 2014 The Authors. Published by Elsevier Inc. All rights reserved.",
year = "2014",
doi = "10.1016/j.molcel.2014.03.018",
language = "English",
volume = "54",
pages = "335--348",
journal = "Molecular Cell",
issn = "1097-2765",
publisher = "Cell Press",
number = "3",

}

RIS

TY - JOUR

T1 - Molecular basis and regulation of OTULIN-LUBAC interaction

AU - Elliott, Paul R.

AU - Al-Saoudi, Sofie Vincents

AU - Marco-Casanova, Paola

AU - Fiil, Berthe Katrine

AU - Keusekotten, Kirstin

AU - Mailand, Niels

AU - Freund, Stefan M. V.

AU - Gyrd-Hansen, Mads

AU - Komander, David

N1 - Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

PY - 2014

Y1 - 2014

N2 - The linear ubiquitin (Ub) chain assembly complex (LUBAC) generates Met1-linked "linear" Ub chains that regulate the activation of the nuclear factor κB (NFκB) transcription factor and other processes. We recently discovered OTULIN as a deubiquitinase that specifically cleaves Met1-linked polyUb. Now, we show that OTULIN binds via a conserved PUB-interacting motif (PIM) to the PUB domain of the LUBAC component HOIP. Crystal structures and nuclear magnetic resonance experiments reveal the molecular basis for the high-affinity interaction and explain why OTULIN binds the HOIP PUB domain specifically. Analysis of LUBAC-induced NFκB signaling suggests that OTULIN needs to be present on LUBAC in order to restrict Met1-polyUb signaling. Moreover, LUBAC-OTULIN complex formation is regulated by OTULIN phosphorylation in the PIM. Phosphorylation of OTULIN prevents HOIP binding, whereas unphosphorylated OTULIN is part of the endogenous LUBAC complex. Our work exemplifies how coordination of ubiquitin assembly and disassembly activities in protein complexes regulates individual Ub linkage types.

AB - The linear ubiquitin (Ub) chain assembly complex (LUBAC) generates Met1-linked "linear" Ub chains that regulate the activation of the nuclear factor κB (NFκB) transcription factor and other processes. We recently discovered OTULIN as a deubiquitinase that specifically cleaves Met1-linked polyUb. Now, we show that OTULIN binds via a conserved PUB-interacting motif (PIM) to the PUB domain of the LUBAC component HOIP. Crystal structures and nuclear magnetic resonance experiments reveal the molecular basis for the high-affinity interaction and explain why OTULIN binds the HOIP PUB domain specifically. Analysis of LUBAC-induced NFκB signaling suggests that OTULIN needs to be present on LUBAC in order to restrict Met1-polyUb signaling. Moreover, LUBAC-OTULIN complex formation is regulated by OTULIN phosphorylation in the PIM. Phosphorylation of OTULIN prevents HOIP binding, whereas unphosphorylated OTULIN is part of the endogenous LUBAC complex. Our work exemplifies how coordination of ubiquitin assembly and disassembly activities in protein complexes regulates individual Ub linkage types.

U2 - 10.1016/j.molcel.2014.03.018

DO - 10.1016/j.molcel.2014.03.018

M3 - Journal article

VL - 54

SP - 335

EP - 348

JO - Molecular Cell

JF - Molecular Cell

SN - 1097-2765

IS - 3

ER -

ID: 110602668