SPATA2-Mediated Binding of CYLD to HOIP Enables CYLD Recruitment to Signaling Complexes
Open accessAbstract
Recruitment of the deubiquitinase CYLD to signaling complexes is mediated by its interaction with HOIP, the catalytically active component of the linear ubiquitin chain assembly complex (LUBAC). Here, we identify SPATA2 as a constitutive direct binding partner of HOIP that bridges the interaction between CYLD and HOIP. SPATA2 recruitment to TNFR1- and NOD2-signaling complexes is dependent on HOIP, and loss of SPATA2 abolishes CYLD recruitment. Deficiency in SPATA2 exerts limited effects on gene activation pathways but diminishes necroptosis induced by tumor necrosis factor (TNF), resembling loss of CYLD. In summary, we describe SPATA2 as a previously unrecognized factor in LUBAC-dependent signaling pathways that serves as an adaptor between HOIP and CYLD, thereby enabling recruitment of CYLD to signaling complexes.
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Necroptosis relies on deubiquitinating activity of CYLD, which is also proteolytic target of CASP8.
“Accordingly, necroptosis relies on the deubiquitinating activity of CYLD [338], which is also a proteolytic target of CASP8 [494–496].”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [494]
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References 42 · Cited by 135
- Authors
- Kupka, S., De Miguel, D., Draber, P., Martino, L., Surinova, S., Rittinger, K., & Walczak, H.
- Affiliations
- University College London (GB)
- The Francis Crick Institute (GB)
- Corresponding author
- Walczak, Henning
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2016-08
- Volume
- 16
- Issue
- 9
- Pages
- 2271-2280
- ISSN
- 2211-1247 (ISSN-L)
- PMC
- PMC5009064
- OpenAlex
- W2517895740
- Cited by
- 135
- References
- 42
- Citations by year
- 2026: 7 · 2025: 6 · 2024: 6 · 2023: 9 · 2022: 18 · 2021: 17 · 2020: 13 · 2019: 20 · 2018: 16 · 2017: 20 · 2016: 3
- FWCI
- 8.19
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cell Reports (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- UCL Discovery (University College London) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- Funders
- Wellcome Trust (508528)
- Francis Crick Institute (10142)
- Cancer Research UK (A17341, 17341)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- CYLD, HOIP, LUBAC, TNFR1 signaling, NOD2 signaling, necroptosis, TNF-α, adaptor proteins, signaling complex assembly
- MeSH terms
- Deubiquitinating Enzyme CYLD, Animals, Binding Sites, Cloning, Molecular, Escherichia coli, Gene Expression Regulation, HeLa Cells, Humans, Macrophages, Plasmids, Protein Binding, Proteins, Recombinant Proteins, Tumor Necrosis Factor-alpha, Signal Transduction, Tumor Suppressor Proteins, Ubiquitin, Ubiquitin-Protein Ligases, Receptors, Tumor Necrosis Factor, Type I, Mice, Nod2 Signaling Adaptor Protein, Primary Cell Culture
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