The IFNAR1 subunit of the type IIFN receptor complex contains a functional nuclear localization sequence

A nuclear localization sequence (NLS) in the type II interferon (IFN) IFNgamma, which is responsible for the nuclear translocation of both the ligand and the alpha-subunit (IFNGR1) of the receptor complex, has previously been characterized and its role in signaling examined in detail. We have now identified an NLS in the type I IFN receptor (IFNAR) common subunit IF-NAR1 from humans and show that the human IFNAR1 subunit can translocate to the nucleus following human IFNbeta stimulation. An NLS in human IFNAR1 is located in the extracellular domain of IFNAR1 within the sequence (RKIIEKKT)-R-382 (numbered for the precursor form). Nuclear import by the NLS functions in a conventional fashion requiring cytosolic import factors, is energy-dependent and inhibited by the prototypical NLS of the SV40 large T-antigen. These studies provide a mechanism for nuclear import of IFNARI, as well as for type I IFN ligands, and a starting point for studying an alternate role for IFNARI in nuclear signaling within the type I IFN system. (C) 2004 Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies.