Keeping Cell Death in Check: Ubiquitylation-Dependent Control of TNFR1 and TLR Signaling

Pro-inflammatory signaling pathways, induced by pathogens, tissue damage or cytokines, depend on the ubiquitylation of various subunits of receptor signaling complexes, controlled by ubiquitin ligases and deubiquitinases. Ubiquitylation sets the stage for the activation of kinases within these receptor complexes, which ultimately regulate pro-inflammatory gene expression. The receptors, which transduce pro-inflammatory signals, can often induce cell death, which is controlled by ubiquitylation as well. In this review, we discuss the key role of ubiquitylation in pro-inflammatory signaling by TNFR1 and TLRs and its role in setting the threshold for cell death induced by these pro-inflammatory triggers.