NUCLEAR ACCUMULATION OF INTERFERON-GAMMA

Examination of the interferon gamma (IFN-gamma) amino acid sequence re vealed two conserved basic amino acid clusters similar to the prototyp e nuclear localization signal. We followed the fate of cell surface re ceptor-bound IFN-gamma in murine leukemia L1210 cells. A time- and tem perature-dependent accumulation of murine IFN-gamma in the cell nucleu s could be demonstrated by autoradiography and indirect immunofluoresc ence after the rapid isolation of nuclei. Human IFN-gamma was also int ernalized and translocated to the nucleus of murine L1210 cells transf ected with and expressing the human IFN-gamma receptor, but it appeare d to be retained by the nucleus only transiently. IFN-gamma molecules chemically crosslinked to their cell surface receptor remain capable o f being translocated to the nucleus even as part of a receptor-ligand complex. Thus, the bipartite nuclear localization signal sequence appe ars to be functional and suggests that nuclear targeting could partici pate in IFN-gamma signal transduction.