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Proc Natl Acad Sci U S A. 2008 Dec 30;105(52):20906-11. doi: 10.1073/pnas.0807975106. Epub 2008 Dec 12.

Cloning and characterization of SARI (suppressor of AP-1, regulated by IFN).

Author information

1
Department of Human and Molecular Genetics, Virginia Commonwealth University School of Medicine, Richmond, VA 23298, USA.

Abstract

We describe a novel basic leucine zipper containing type I IFN-inducible early response gene SARI (Suppressor of AP-1, Regulated by IFN). Steady-state SARI mRNA expression was detected in multiple lineage-specific normal cells, but not in their transformed/tumorigenic counterparts. In normal and cancer cells, SARI expression was induced 2 h after fibroblast IFN (IFN-beta) treatment with 1 U/ml of IFN-beta. Antisense inhibition of SARI protected HeLa cells from IFN-beta-mediated growth inhibition. As a corollary, overexpression of SARI inhibited growth and induced apoptosis in cancer cells, but not in normal cells. SARI interacted with c-Jun via its leucine zipper, resulting in inhibition of DNA binding of activator protein (AP-1) complex and consequently AP-1-dependent gene expression. Transformed cells relying on AP-1 activity for proliferative advantage demonstrated increased susceptibility to SARI-mediated growth inhibition. These findings uncover a novel mode of IFN-induced anti-tumor growth suppression and suggest potential gene therapy applications for SARI.

PMID:
19074269
PMCID:
PMC2634918
DOI:
10.1073/pnas.0807975106
[Indexed for MEDLINE]
Free PMC Article

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