CYTOKINE INDUCTION OF NUCLEAR FACTOR KAPPA-B IN CYCLING AND GROWTH-ARRESTED CELLS - EVIDENCE FOR CELL CYCLE-INDEPENDENT ACTIVATION

Nuclear factor kappa B (NF-kappa B) is a pleiotropic transcription factor which regulates the expression of a large number of cellular and viral genes. Induction of NF-kappa B has been shown previously to occur during cell cycle transition from G(0) to G(1), but the relationship of cytokine induction of this transcription factor to cell cycling has not been directly addressed. Here we examine the induction of NF-kappa B in serum-deprived and cycling cells in response to tumor necrosis factor-alpha (TNF-alpha). In 3T3 fibroblasts deprived of serum, and in the temperature-sensitive G(2) phase mutant carcinoma line FT210, we find that NF-kappa B DNA binding activity is rapidly induced upon addition of TNF-alpha. In addition, NF-kappa B induction in cycling cells occurs without a significant change in cell cycle distribution. These data reveal that NF-kappa B is rapidly induced by TNF-alpha in both proliferating and arrested cells and suggest that distinct activation pathways can lead to cell cycle-dependent or -independent induction of NF-kappa B.