Cytokine induction of nuclear factor κB in cycling and growth-arrested cells: Evidence for cell cycle-independent activation

Nuclear factor κB (NF-κB) is a pleiotropic transcription factor which regulates the expression of a large number of cellular and viral genes. Induction of NF-κB has been shown previously to occur during cell cycle transition from G₀ to G₁, 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-κB in serum-deprived and cycling cells in response to tumor necrosis factor-α (TNF-α). In 3T3 fibroblasts deprived of serum, and in the temperaturesensitive G₂ phase mutant carcinoma line FT210, we find that NF-κB DNA binding activity is rapidly induced upon addition of TNF-α. In addition, NF-κB induction in cycling cells occurs without a significant change in cell cycle distribution. These data reveal that NF-κB is rapidly induced by TNF-α in both proliferating and arrested cells and suggest that distinct activation pathways can lead to cell cycle-dependent or -independent induction of NF-κB.