Emerging Trends for the Regulation of Thiol-Based Redox Transcription Factor Pathways

Thiol-based redox transcription factor
pathways play central roles
in the cellular response to peroxide stress. We review the bacterial
OxyR, yeast AP-1 and mammalian NRF2/Keap1 systems and the principles
underlying the regulation of these pathways. In these systems, peroxides
are sensed by specific thiol residues on a transcription factor or
on a cognate sensor protein, leading to the activation of the transcription
factor. However, transcription factor activity also depends on the
oxidizing and reducing activities within their respective reaction
networks. The transcriptional targets induced by these transcription
factors include antioxidant defense genes and, significantly, genes
required for meeting other cellular demands. We then describe new
results on these systems, such as redox microdomains, signal transmission
dynamics and phenotypic heterogeneity, which have extended our understanding
of redox signaling. These results emphasize the multifaceted nature
of the adaptive response to oxidative stress and provide connections
to other cellular pathways that are critical for cell physiology.