2. Academic Validation
  3. SPATA2-Mediated Binding of CYLD to HOIP Enables CYLD Recruitment to Signaling Complexes

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.
Sebastian Kupka 1,  Diego De Miguel 1,  Peter Draber 1,  Luigi Martino 2,  Silvia Surinova 1,  Katrin Rittinger 2,  Henning Walczak 3
Affiliations

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.
PMID: 27545878 DOI: 10.1016/j.celrep.2016.07.086
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.

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