AIP1: a new player in TNF signaling

The signaling system generated by the binding of TNF to its cognate TNFreceptor (TNF-R) can contain two distinct type I transmembrane receptors, TNF-R1 and TNF-R2, and three ligands, the membrane-bound TNF-, the soluble TNF-, and the soluble lymphocyte-derived cytokine lymphotoxin- (LT-) (1).Both receptors are ubiquitously expressed in cells and interact with both forms of TNF-, as well as with LT-.However, TNF-R1 is the most potent in inducing cytotoxic signals.TNF-R1 is a typical death receptor with a 60-to 80-amino acid cytoplasmic sequence known as the death domain.The death domain, which is missing from TNF-R2, typically enables death receptors to initiate cytotoxic signals.Because of the role of TNF- in human diseases (2), TNF-R1 signaling mechanisms are of considerable biomedical interest.