2024-03-29T16:04:43Zhttps://eprints.lib.hokudai.ac.jp/dspace-oai/requestoai:eprints.lib.hokudai.ac.jp:2115/221032022-11-17T02:08:08Zhdl_2115_20044hdl_2115_124Physical and functional interactions between Daxx and STAT3.Muromoto, R.Nakao, K.Watanabe, T.Sato, N.Sekine, Y.Sugiyama, K.Oritani, K.Shimoda, K.Matsuda, T.IL-6LIFSTAT3Daxxtranscriptional regulation499Signal transducer and activator of transcription 3 (STAT3) play key roles in the intracellular signaling pathways of the interleukin (IL)-6 family of cytokines, which exhibit 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 example 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.Nature Publishing GroupJournal Articleapplication/pdfhttp://hdl.handle.net/2115/22103https://eprints.lib.hokudai.ac.jp/dspace/bitstream/2115/22103/1/ONCO25-14.pdf0950-92320950-9232Oncogene2514213121362006-03-30enginfo:pmid/16331268info:doi/10.1038/sj.onc.1209235Nature Publishing Group, ONCOGENE, 25, 14, 2006, 2131-2136.author