| Here we show that IFNAR 1 interacts with the Homolog of Slimb ( HOS ) F box protein in a phosphorylation dependent manner , and that this interaction is promoted by interferon alpha ( IFNalpha ) . ^^^ IFNAR 1 is ubiquitinated by the Skp 1 Cullin1 HOS Roc 1 ( SCF ( HOS ) ) ubiquitin ligase in vitro . ^^^ HOS expression and activities are required for IFNalpha stimulated ubiquitination of IFNAR 1 , endocytosis of the type 1 interferon receptor , down regulation of IFNAR 1 levels , and IFNAR 1 proteolysis via the lysosomal pathway . ^^^ These findings characterize SCF ( HOS ) as an E 3 ubiquitin ligase that is essential for ubiquitination , proteolysis and down regulation of IFNAR 1 , and implicate HOS in the regulation of cellular responses to IFNalpha . . ^^^ |