title: Cloning and characterization of SARI (suppressor of AP-1, regulated by IFN).
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.
authors.affiliation: Department of Human and Molecular Genetics, Virginia Commonwealth University School of Medicine, Richmond, VA 23298, USA.
authors.forename: Zao-zhong
authors.initials: ZZ
authors.lastname: Su
authors.forename: Seok-Geun
authors.initials: SG
authors.lastname: Lee
authors.forename: Luni
authors.initials: L
authors.lastname: Emdad
authors.forename: Irina V
authors.initials: IV
authors.lastname: Lebdeva
authors.forename: Pankaj
authors.initials: P
authors.lastname: Gupta
authors.forename: Kristoffer
authors.initials: K
authors.lastname: Valerie
authors.forename: Devanand
authors.initials: D
authors.lastname: Sarkar
authors.forename: Paul B
authors.initials: PB
authors.lastname: Fisher
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D050976:Basic-Leucine Zipper Transcription Factors / Q000096:biosynthesis* / Q000235:genetics*; D003001:Cloning, Molecular; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000235:genetics*; D006367:HeLa Cells; D006801:Humans; D016899:Interferon-beta / Q000494:pharmacology; D016350:Leucine Zippers / Q000235:genetics; D012097:Repressor Proteins / Q000096:biosynthesis* / Q000235:genetics*; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis* / Q000235:genetics*
chemical_list: D050976:Basic-Leucine Zipper Transcription Factors; C569485:Batf2 protein, human; D012097:Repressor Proteins; D018808:Transcription Factor AP-1; D025521:Tumor Suppressor Proteins; D016899:Interferon-beta