SPATA2-Mediated Binding of CYLD to HOIP Enables CYLD Recruitment to Signaling Complexes.
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, Gene Expression Regulation, HeLa Cells, Humans, Macrophages, Mice, Nod2 Signaling Adaptor Protein, Plasmids, Primary Cell Culture, Protein Binding, Proteins, Receptors, Tumor Necrosis Factor, Type I, Recombinant Proteins, Signal Transduction, Tumor Necrosis Factor-alpha, Tumor Suppressor Proteins, Ubiquitin, Ubiquitin-Protein Ligases
Animals, Binding Sites, Cloning, Molecular, Deubiquitinating Enzyme CYLD, Escherichia coli, Gene Expression Regulation, HeLa Cells, Humans, Macrophages, Mice, Nod2 Signaling Adaptor Protein, Plasmids, Primary Cell Culture, Protein Binding, Proteins, Receptors, Tumor Necrosis Factor, Type I, Recombinant Proteins, Signal Transduction, Tumor Necrosis Factor-alpha, Tumor Suppressor Proteins, Ubiquitin, Ubiquitin-Protein Ligases
Cell Rep
Date: Dec. 30, 2015
PubMed ID: 27545878
View in: Pubmed Google Scholar
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