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

Zao Zhong Su, Seok Geun Lee, Luni Emdad, Irina V. Lebdeva, Pankaj Gupta, Kristoffer Valerie, Devanand Sarkar, Paul B. Fisher

Research output: Contribution to journalArticle

56 Scopus citations

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 languageEnglish (US)
Pages (from-to)20906-20911
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume105
Issue number52
DOIs
StatePublished - Dec 30 2008

Keywords

  • Cancer growth suppressing gene
  • IFN-inducible gene
  • Jun-interacting protein

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