Transport of gamma-interferon into the cell nucleus may be mediated by nuclear membrane receptors.
Purified mouse interferon gamma (MuIFN-gamma), a lymphokine having potent antiviral, immunomodulatory, and growth inhibitory activities, is internalized (t1/2 less than 1.0 min) by mouse L929 fibroblasts via receptor-mediated endocytosis. Individual MuIFN-gamma molecules, identified by a postembedding immuno-gold technique, are then transported to the cell nucleus, perhaps through nuclear pores, into areas of dense chromatin. Purified, isolated nuclei of L929 cells bind radiolabeled MuIFN-gamma specifically and with high affinity (Kd = 2 X 10(-10) M). These nuclear membrane receptors, distinct from those for MuIFN-beta, number about 24,000/nucleus. Treatment of nuclei with trypsin prevents binding of MuIFN-gamma. The demonstration of rapid cellular uptake and transport of MuIFN-gamma into the dense chromatin, perhaps facilitated by nuclear receptors, suggests that IFN-gamma molecules, alone or bound to receptor, may directly affect genome regulation.
D000818:Animals; D001693:Biological Transport, Active; D002467:Cell Nucleus / Q000378:metabolism*; D004705:Endocytosis; D005347:Fibroblasts / Q000378:metabolism; D006207:Half-Life; D007371:Interferon-gamma / Q000378:metabolism*; D007700:Kinetics; D051379:Mice; D009685:Nuclear Envelope / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000378:metabolism*; D017471:Receptors, Interferon
D011971:Receptors, Immunologic; D017471:Receptors, Interferon; D007371:Interferon-gamma