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Sulfiredoxin Is an AP-1 Target Gene That Is Required for Transformation and Shows Elevated Expression in Human Skin Malignancies
Qiou Wei, Hong Jiang, Connie P. Matthews and Nancy H. Colburn
Proceedings of the National Academy of Sciences of the United States of America
Vol. 105, No. 50 (Dec. 16, 2008), pp. 19738-19743
Published by: National Academy of Sciences
Stable URL: http://www.jstor.org/stable/25465718
Page Count: 6
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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.
Proceedings of the National Academy of Sciences of the United States of America © 2008 National Academy of Sciences