Premium
Physical and Functional interactions between Daxx and STAT3
Author(s) -
Matsuda Tadashi,
Muromoto Ryuta,
Nakao Kei,
Watanabe Tadashi,
Sato Noriko,
Sekine Yuichi,
Sugiyma Kenji
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a533-d
Subject(s) - death associated protein 6 , stat3 , stat protein , transcription factor , microbiology and biotechnology , biology , signal transduction , cancer research , chemistry , gene , nuclear protein , genetics
Signal transducer and activator of transcription 3 (STAT3) plays key roles in the intracellular signaling pathways of the interleukin (IL)‐6 family of cytokines, which exhibits a diverse set of cellular responses, including cell proliferation and differentiation. Dysregulated IL‐6/STAT3 signaling is involved in the pathogenesis of several diseases, for examples autoimmune diseases and tumors. Type I interferon (IFN) induces the expression of proapoptotic genes and has been used in the clinical treatment of several tumors. In the present study, we found that type I IFN suppressed IL‐6/STAT3‐mediated transcription and gene expression. Furthermore, a type I IFN‐induced protein, Daxx, also suppressed STAT3‐mediated transcriptional activation, while overexpression of Daxx inhibited IL‐6/STAT3‐mediated gene expression. Importantly, small‐interfering RNA‐mediated reduction of Daxx expression enhanced IL‐6/leukemia inhibitory factor (LIF)‐induced STAT3‐dependent transcription. Co‐immunoprecipitation studies revealed a physical interaction between Daxx and STAT3 in transiently transfected 293T cells. We further found that Daxx and STAT3 were co‐localized in the nucleus. These results indicate that Daxx may serve as a transcriptional regulator of type I IFN‐mediated suppression of the IL‐6/STAT3 signaling pathway.