SKN3

SKN3 is a gene that encodes a transcription factor in the budding yeast Saccharomyces cerevisiae. The gene is located on chromosome XV and produces a protein of approximately 269 amino acids. SKN3 contains a DNA‑binding domain typical of the HSF‑C family of transcription factors and a leucine‑zipper motif that mediates protein–protein interactions.

The Skn3 protein functions primarily in the cellular oxidative stress response. Under normal growth conditions it is largely cytoplasmic, but exposure to reactive oxygen species or other stressors triggers its rapid translocation into the nucleus. Once in the nucleus, Skn3 binds to antioxidant response elements in the promoters of target genes and activates transcription of enzymes involved in glutathione synthesis, catalase activity, and other detoxification pathways. Skn3 acts both independently and cooperatively with other known yeast stress regulators such as Yap1, contributing to a coordinated defense against oxidative damage.

Functional studies have shown that skn3Δ strains (deletions of the SKN3 locus) display increased sensitivity to hydrogen peroxide, menadione, and other oxidants, indicating a critical role for Skn3 in maintaining redox homeostasis. Overexpression of SKN3 can partially rescue the oxidative stress phenotypes of mutants lacking other antioxidant genes, suggesting that Skn3 can compensate for certain deficiencies in the oxidative stress network.

The SKN3 protein is highly conserved across fungal species, and its homologs in other organisms exhibit similar regulatory roles in response to environmental stress. In metazoans, the functional analog of Skn3 is the transcription factor Nrf2, which activates a broad spectrum of cytoprotective genes following oxidative insult. While Skn3 itself is not known to participate in human disease directly, its study provides insights into the evolution of redox‑responsive transcriptional networks and may inform therapeutic strategies targeting oxidative stress in higher eukaryotes.