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    Proc Natl Acad Sci U S A. 2008 Dec 16;105(50):19738-43. Epub 2008 Dec 4.

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

    Wei Q, Jiang H, Matthews CP, Colburn NH.

    Source

    Laboratory of Cancer Prevention, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA.

    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.

    PMID:
    19057013
    [PubMed - indexed for MEDLINE]
    PMCID:
    PMC2604998
    Free PMC Article

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