SPATA2 – Keeping the TNF signal short and sweet

Abstract

In this issue of The EMBO Journal, a multi-layered global proteome resource, which comprehensively covers TNF-induced phosphorylation and ubiquitination events as well as receptor interactions, has led to identification of SPATA2 as a novel player that contributes to TNF signalling by interacting with the LUBAC ubiquitin ligase and the CYLD deubiquitylase. Loss of SPATA2 augments transcriptional activation of NF-κB and limits TNF-induced necroptosis. A separate screen published in EMBO Reports corroborates these findings by showing that SPATA2 deficiency regulates CYLD activity, TNF-induced NF-κB signalling and cell death.