SPATA2-mediated binding of CYLD to HOIP enables CYLD recruitment to signaling complexes
journal contributionposted on 2020-08-20, 16:27 authored by Sebastian Kupka, Diego De Miguel, Peter Draber, Luigi Martino, Silvia Surinova, Katrin Rittinger, Henning Walczak
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.
AnimalsBinding SitesCloning, MolecularDeubiquitinating Enzyme CYLDEscherichia coliGene Expression RegulationHeLa CellsHumansMacrophagesMiceNod2 Signaling Adaptor ProteinPlasmidsPrimary Cell CultureProtein BindingProteinsReceptors, Tumor Necrosis Factor, Type IRecombinant ProteinsSignal TransductionTumor Necrosis Factor-alphaTumor Suppressor ProteinsUbiquitinUbiquitin-Protein LigasesHela CellsRittinger FC001142PC-ack0601 Biochemistry and Cell Biology