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-β) treatment with 1 U/ml of IFN-β. Antisense inhibition of SARI protected HeLa cells from IFN-β-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.
Original language | English (US) |
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Pages (from-to) | 20906-20911 |
Number of pages | 6 |
Journal | Proceedings of the National Academy of Sciences of the United States of America |
Volume | 105 |
Issue number | 52 |
DOIs | |
State | Published - Dec 30 2008 |
Keywords
- Cancer growth suppressing gene
- IFN-inducible gene
- Jun-interacting protein