Regulation of TNFRSF and innate immune signalling complexes by TRAFs and cIAPs

There have been a number of recent discoveries relating to the functions of inhibitors of apoptosis (IAPs) and TNF receptor-associated factors (TRAFs) in regulating signalling from TNF receptor superfamily (TNFRSF) members and some tantalizing glimpses into a wider area of influence, that of innate immune signalling. Discoveries relating to the function of these ubiquitin E3 ligases in regulating signalling from the eponymous member of the family, TNF-R1, are dealt with superbly in a separate review by Wertz and Dixit and so we will confine our discussion to the subset of the TNFRSF that does not contain a death domain (DD). In line with the available data we will divide the review into two parts, the first is restricted to the role of TRAFs 2 and 3 and cIAPs in regulating TNFRSF signalling, whereas the second will be more speculative, asking what role IAPs and TRAFs have in innate immune signalling. Cell Death and Differentiation (2010) 17, 35-45; doi:10.1038/cdd.2009.114; published online 14 August 2009