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

  1. Author:
    Wei, Q.
    Jiang, H.
    Matthews, C. P.
    Colburn, N. H.

  2. Author Address

    Wei, Qiou, Jiang, Hong, Matthews, Connie P.; Colburn, Nancy H.] Natl Canc Inst, Lab Canc Prevent, Ctr Canc Res, Frederick, MD 21701 USA.
    1. Year: 2008
  2. Journal: Proceedings of the National Academy of Sciences of the United States of America
    1. 105
    2. 50
    3. Pages: 19738-19743
  4. Type of Article: Article
  1. Abstract:

    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.

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External Sources

  1. PMID: 19057013

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