SPATA2-Mediated Binding of CYLD to HOIP Enables CYLD Recruitment to Signaling Complexes

Sebastian Kupka; Diego De Miguel; Peter Draber; Luigi Martino; Silvia Surinova; Katrin Rittinger; Henning Walczak

doi:10.1016/j.celrep.2016.07.086

SPATA2-Mediated Binding of CYLD to HOIP Enables CYLD Recruitment to Signaling Complexes

Cell Rep. 2016 Aug 30;16(9):2271-80. doi: 10.1016/j.celrep.2016.07.086. Epub 2016 Aug 18.

Authors

Sebastian Kupka¹, Diego De Miguel¹, Peter Draber¹, Luigi Martino², Silvia Surinova¹, Katrin Rittinger², Henning Walczak³

Affiliations

¹ Centre for Cell Death, Cancer, and Inflammation (CCCI), UCL Cancer Institute, University College London, 72 Huntley Street, London WC1E 6DD, UK.
² The Francis Crick Institute, 1 Midland Road, London NW1 1BF, UK.
³ Centre for Cell Death, Cancer, and Inflammation (CCCI), UCL Cancer Institute, University College London, 72 Huntley Street, London WC1E 6DD, UK. Electronic address: h.walczak@ucl.ac.uk.

Abstract

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.

MeSH terms

Animals
Binding Sites
Cloning, Molecular
Deubiquitinating Enzyme CYLD
Escherichia coli / genetics
Escherichia coli / metabolism
Gene Expression Regulation
HeLa Cells
Humans
Macrophages / cytology
Macrophages / drug effects
Macrophages / metabolism*
Mice
Nod2 Signaling Adaptor Protein / genetics
Nod2 Signaling Adaptor Protein / metabolism
Plasmids
Primary Cell Culture
Protein Binding
Proteins / genetics
Proteins / metabolism*
Receptors, Tumor Necrosis Factor, Type I / genetics
Receptors, Tumor Necrosis Factor, Type I / metabolism
Recombinant Proteins / genetics
Recombinant Proteins / metabolism
Signal Transduction*
Tumor Necrosis Factor-alpha / pharmacology
Tumor Suppressor Proteins / genetics
Tumor Suppressor Proteins / metabolism*
Ubiquitin / genetics
Ubiquitin / metabolism*
Ubiquitin-Protein Ligases / genetics
Ubiquitin-Protein Ligases / metabolism*

Substances

NOD2 protein, human
Nod2 Signaling Adaptor Protein
Proteins
Receptors, Tumor Necrosis Factor, Type I
Recombinant Proteins
SPATA2 protein, human
Tumor Necrosis Factor-alpha
Tumor Suppressor Proteins
Ubiquitin
RNF31 protein, human
Ubiquitin-Protein Ligases
CYLD protein, human
Deubiquitinating Enzyme CYLD

Abstract

MeSH terms

Substances

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