SCFHOS ubiquitin ligase mediates the ligand-induced down-regulation of the interferon-  receptor

Down-regulation of activated signaling receptors in response to their ligands plays a key role in restricting the extent and duration of the signaling. Mechanisms underlying down-regulation of the type I interferon receptor consisting of IFNAR1 and IFNAR2 subunits remain largely unknown. Here we show that IFNAR1 interacts with the Homolog of Slimb (HOS) F-box protein in a phosphorylation-dependent manner, and that this interaction is promoted by interferon [alpha] (IFN[alpha]). IFNAR1 is ubiquitinated by the Skp1-Cullin1-HOS-Roc1 (SCF