IFR-9/STAT2 Functional Interaction Drives Retinoic Acid–Induced Gene G Expression Independently of STAT1
Open Access
- 15 April 2009
- journal article
- Published by American Association for Cancer Research (AACR) in Cancer Research
- Vol. 69 (8), 3673-3680
- https://doi.org/10.1158/0008-5472.can-08-4922
Abstract
Retinoic acid–induced gene G (RIG-G), a gene originally identified in all-trans retinoic acid–treated NB4 acute promyelocytic leukemia cells, is also induced by IFNα in various hematopoietic and solid tumor cells. Our previous work showed that RIG-G possessed a potent antiproliferative activity. However, the mechanism for the transcriptional regulation of RIG-G gene remains unknown. Here, we report that signal transducer and activator of transcription (STAT) 2 together with IFN regulatory factor (IRF)-9 can effectively drive the transcription of RIG-G gene by their functional interaction through a STAT1-independent manner, even without the tyrosine phosphorylation of STAT2. The complex IRF-9/STAT2 is both necessary and sufficient for RIG-G gene expression. In addition, IRF-1 is also able to induce RIG-G gene expression through an IRF-9/STAT2–dependent or IRF-9/STAT2–independent mechanism. Moreover, the induction of RIG-G by retinoic acid in NB4 cells resulted, to some extent, from an IFNα autocrine pathway, a finding that suggests a novel mechanism for the signal cross-talk between IFNα and retinoic acid. Taken together, our results provide for the first time the evidence of the biological significance of IRF-9/STAT2 complex, and furnish an alternative pathway modulating the expression of IFN-stimulated genes, contributing to the diversity of IFN signaling to mediate their multiple biological properties in normal and tumor cells. [Cancer Res 2009;69(8):3673–80]Keywords
This publication has 36 references indexed in Scilit:
- Organization of the mouse RNA-specific adenosine deaminase Adar1 gene 5′-region and demonstration of STAT1-independent, STAT2-dependent transcriptional activation by interferonVirology, 2008
- IFN-γ-induced expression of MUC4 in pancreatic cancer cells is mediated by STAT-1 upregulation: a novel mechanism for IFN-γ responseOncogene, 2007
- Unphosphorylated STAT3 accumulates in response to IL-6 and activates transcription by binding to NFκBGenes & Development, 2007
- Unphosphorylated STAT6 contributes to constitutive cyclooxygenase-2 expression in human non-small cell lung cancerOncogene, 2007
- RIG-G as a key mediator of the antiproliferative activity of interferon-related pathways through enhancing p21 and p27 proteinsProceedings of the National Academy of Sciences of the United States of America, 2006
- Viruses Evade the Immune System through Type I Interferon-Mediated STAT2-Dependent, but STAT1-Independent, SignalingImmunity, 2005
- Complex Formation of the Interferon (IFN) Consensus Sequence-binding Protein with IRF-1 Is Essential for Murine Macrophage IFN-γ-induced iNOS Gene ExpressionPublished by Elsevier BV ,2003
- The Cell Cycle Control Element of Histone H4 Gene Transcription Is Maximally Responsive to Interferon Regulatory Factor Pairs IRF-1/IRF-3 and IRF-1/IRF-7Published by Elsevier BV ,2001
- How Stat1 mediates constitutive gene expression: a complex of unphosphorylated Stat1 and IRF1 supports transcription of the LMP2 geneThe EMBO Journal, 2000
- Stat2 Is a Transcriptional Activator That Requires Sequence-specific Contacts Provided by Stat1 and p48 for Stable Interaction with DNAPublished by Elsevier BV ,1997