Intracellular oxidation/reduction status in the regulation of transcription factors NF-kappaB and AP-1.

The eukaryotic cell contains a multitude of pathways coupling environmental stimuli to the specific regulation of gene expression. Two early response transcriptional complexes, NF-kappaB and AP-1, appear to respond to environmental stressors by inducing the expression of response specific downstream genes. Both are well-characterized transcriptional regulatory factors that are induced by a wide variety of seemingly unrelated exogenous and endogenous agents and serve important roles in cell growth and differentiation, immunity, inflammation, and other preprogrammed cellular genetic processes. The activities of NF-kappaB and AP-1 are also affected following exposure to chemicals, drugs, or other agents that appear to alter the cellular oxidation/reduction (redox) status. From these observations, it has been suggested that changes in cellular oxidation/reduction status, communicated via a series of cellular redox-sensitive signaling circuitry employing metal- and thiol-containing proteins, serve as common mechanisms linking environmental stressors to adaptive cellular responses. As such, these transcription factors are ideal paradigms to study the mechanism and possible physiological significance of early response genes in the cellular response to changes in cellular redox status. In this article we summarize the evidence suggesting that cellular redox regulates these transcription factors.