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

Kupka, S; De Miguel, D; Draber, P; Martino, L; Surinova, S; Rittinger, K; Walczak, H; (2016) SPATA2-Mediated Binding of CYLD to HOIP Enables CYLD Recruitment to Signaling Complexes. Cell Reports , 16 (9) pp. 2271-2280. 10.1016/j.celrep.2016.07.086. Green open access

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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.

Type: Article
Title: SPATA2-Mediated Binding of CYLD to HOIP Enables CYLD Recruitment to Signaling Complexes
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.celrep.2016.07.086
Publisher version: http://dx.doi.org/10.1016/j.celrep.2016.07.086
Language: English
Additional information: © 2016 The Authors. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Keywords: Science & Technology, Life Sciences & Biomedicine, Cell Biology, NF-KAPPA-B, DEUBIQUITINATING ENZYME CYLD, LINEAR UBIQUITIN CHAINS, CELL-DEATH, ASSEMBLY COMPLEX, INNATE IMMUNITY, LUBAC, INFLAMMATION, APOPTOSIS, OTULIN
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Cancer Bio
URI: http://discovery.ucl.ac.uk/id/eprint/1508764
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