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IFR-9/STAT2 Functional Interaction Drives Retinoic Acid–Induced Gene G Expression Independently of STAT1

Shanghai Institute of Hematology and State Key Laboratory of Medical Genomics, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China

Requests for reprints: Jian-Hua Tong, Shanghai Institute of Hematology, Rui-Jin Hospital, 197 Rui-Jin Road II, Shanghai 200025, People's Republic of China. Phone/Fax: 86-21-64743206; E-mail: jhtong{at}yahoo.com.

Key Words: gene expression • IRF-9 • RIG-G • signal transduction • STAT2

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 IFN 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 IFN autocrine pathway, a finding that suggests a novel mechanism for the signal cross-talk between IFN 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]

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				Correction: Article on IRF-9/STAT2 Drives the Expression of RIG-G Gene Cancer Res., May 15, 2009; 69(10): 4553 - 4553. [Full Text] [PDF]