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Cited by 482

The DOI matches its Crossref record; 56 of the 56 references it cites were found in a registry or an index.

OTULIN Antagonizes LUBAC Signaling by Specifically Hydrolyzing Met1-Linked Polyubiquitin

Open access
Keusekotten, Kirstin, Elliott, Paul Ronald, Glockner, Laura, Fiil, Berthe Katrine, Damgaard, Rune Busk, Kulathu, Yogesh, Wauer, Tobias, Hospenthal, Manuela Kathrin, Gyrd-Hansen, Mads, Krappmann, Daniel, Hofmann, Kay, Komander, David·2013·Cell
DOI 10.1016/j.cell.2013.05.014
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Abstract

The linear ubiquitin (Ub) chain assembly complex (LUBAC) is an E3 ligase that specifically assembles Met1-linked (also known as linear) Ub chains that regulate nuclear factor κB (NF-κB) signaling. Deubiquitinases (DUBs) are key regulators of Ub signaling, but a dedicated DUB for Met1 linkages has not been identified. Here, we reveal a previously unannotated human DUB, OTULIN (also known as FAM105B), which is exquisitely specific for Met1 linkages. Crystal structures of the OTULIN catalytic domain in complex with diubiquitin reveal Met1-specific Ub-binding sites and a mechanism of substrate-assisted catalysis in which the proximal Ub activates the catalytic triad of the protease. Mutation of Ub Glu16 inhibits OTULIN activity by reducing kcat 240-fold. OTULIN overexpression or knockdown affects NF-κB responses to LUBAC, TNFα, and poly(I:C) and sensitizes cells to TNFα-induced cell death. We show that OTULIN binds LUBAC and that overexpression of OTULIN prevents TNFα-induced NEMO association with ubiquitinated RIPK1. Our data suggest that OTULIN regulates Met1-polyUb signaling.

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Metadata

Authors
Keusekotten, K., Elliott, P. R., Glockner, L., Fiil, B. K., Damgaard, R. B., Kulathu, Y., Wauer, T., Hospenthal, M. K., Gyrd-Hansen, M., Krappmann, D., Hofmann, K., & Komander, D.
Venue
Cell
Publisher
Elsevier BV
Published
2013-06
Volume
153
Issue
6
Pages
1312-1326
ISSN
0092-8674 (ISSN-L)
DOI
10.1016/j.cell.2013.05.014
OpenAlex
W2152630268
Cited by
482
References
56
FWCI
15.73
Type
journal article
Language
en
Open access
hybrid

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CoChat. (2026). Citation check: OTULIN Antagonizes LUBAC Signaling by Specifically Hydrolyzing Met1-Linked Polyubiquitin. https://app.cochat.ai/papers/10.1016/j.cell.2013.05.014
The paper
Keusekotten, K., Elliott, P. R., Glockner, L., Fiil, B. K., Damgaard, R. B., Kulathu, Y., Wauer, T., Hospenthal, M. K., Gyrd-Hansen, M., Krappmann, D., Hofmann, K., & Komander, D. (2013). OTULIN Antagonizes LUBAC Signaling by Specifically Hydrolyzing Met1-Linked Polyubiquitin. Cell. https://doi.org/10.1016/j.cell.2013.05.014

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.