Nuclear Accumulation of Interferon γ

• Published in: Proceedings of the National Academy of Sciences - PNAS 1994-12, Vol.91 (25), p.11831-11835
• Main Authors: Bader, Thomas, Wietzerbin, Juana
• Format: Article
• Language: English
• Subjects: Amino acids; Animals; Autoradiography; Cell lines; Cell nucleus; Cell Nucleus - metabolism; Cell Nucleus - ultrastructure; Cell surface receptors; Cells; Cellular biology; Fluorescent Antibody Technique; Humans; Immunity (Disease); Interferon gamma Receptor; Interferon-gamma - metabolism; Interferons; Internalization; Iodine Radioisotopes; Kinetics; Leukemia L1210 - metabolism; Ligands; Mice; Receptors; Receptors, Interferon - biosynthesis; Receptors, Interferon - metabolism; Recombinant Proteins - biosynthesis; Recombinant Proteins - metabolism; Tumor Cells, Cultured
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.91.25.11831

Examination of the interferon γ (IFN-γ) amino acid sequence revealed two conserved basic amino acid clusters similar to the prototype nuclear localization signal. We followed the fate of cell surface receptor-bound IFN-γ in murine leukemia L1210 cells. A time- and temperature-dependent accumulation of murine IFN-γ in the cell nucleus could be demonstrated by autoradiography and indirect immunofluorescence after the rapid isolation of nuclei. Human IFN-γ was also internalized and translocated to the nucleus of murine L1210 cells transfected with and expressing the human IFN-γ receptor, but it appeared to be retained by the nucleus only transiently. IFN-γ molecules chemically crosslinked to their cell surface receptor remain capable of being translocated to the nucleus even as part of a receptor-ligand complex. Thus, the bipartite nuclear localization signal sequence appears to be functional and suggests that nuclear targeting could participate in IFN-γ signal transduction.