Sulfiredoxin is an AP-1 target gene that is required for transformation and shows elevated expression in human skin malignancies

Q Wei, H Jiang, CP Matthews… - Proceedings of the …, 2008 - National Acad Sciences
Q Wei, H Jiang, CP Matthews, NH Colburn
Proceedings of the National Academy of Sciences, 2008National Acad Sciences
Previous studies have shown that a dominant negative form of c-Jun (TAM67) suppresses
mouse skin carcinogenesis both in vitro and in vivo. The current study identifies Sulfiredoxin
(Srx) as a unique target of activator protein-1 (AP-1) activation and TAM67 inhibition.
Manipulation of Srx levels by ShRNA or over-expression demonstrates that Srx is critical for
redox homeostasis through reducing hyperoxidized peroxiredoxins. In JB6 cells, knockdown
of Srx abolishes tumor promoter-induced transformation and enhances cell sensitivity to …
Previous studies have shown that a dominant negative form of c-Jun (TAM67) suppresses mouse skin carcinogenesis both in vitro and in vivo. The current study identifies Sulfiredoxin (Srx) as a unique target of activator protein-1 (AP-1) activation and TAM67 inhibition. Manipulation of Srx levels by ShRNA or over-expression demonstrates that Srx is critical for redox homeostasis through reducing hyperoxidized peroxiredoxins. In JB6 cells, knockdown of Srx abolishes tumor promoter-induced transformation and enhances cell sensitivity to oxidative stress. Knockdown of Srx also impairs c-Jun phosphorylation, implicating a role for Srx in the feedback regulation of AP-1 activity. Screening of patient tissues by tissue microarray reveals elevated Srx expression in several types of human skin cancers. Our study indicates that Srx is a functionally significant target of AP-1 blockade that may have value in cancer prevention or treatment.
National Acad Sciences