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

Authors
  • Su, Zao-zhong
  • Lee, Seok-Geun
  • Emdad, Luni
  • Lebdeva, Irina V
  • Gupta, Pankaj
  • Valerie, Kristoffer
  • Sarkar, Devanand
  • Fisher, Paul B
Type
Published Article
Journal
Proceedings of the National Academy of Sciences
Publisher
Proceedings of the National Academy of Sciences
Publication Date
Dec 30, 2008
Volume
105
Issue
52
Pages
20906–20911
Identifiers
DOI: 10.1073/pnas.0807975106
PMID: 19074269
Source
Medline
License
Unknown

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.

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