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Physical and functional interactions between Daxx and STAT3

Oncogene volume 25, pages 2131–2136 (2006)Cite this article

Abstract

Signal 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.

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Acknowledgements

This work was supported in part by grants from the Osaka Foundation for Promotion of Clinical Immunology, the Naito Foundation, the Akiyama Foundation and the Sasakawa Scientific Research Grant from The Japan Science Society.

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Author notes

  1. R Muromoto and K Nakao: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Immunology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo, Hokkaido, Japan

    R Muromoto, K Nakao, T Watanabe, N Sato, Y Sekine & T Matsuda

  2. Nippon Boehringer Ingelheim Co. Ltd, Kawanishi Pharma Research Institute, Kawanishi, Hyogo, Japan

    K Sugiyama

  3. Department of Hematology and Oncology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan

    K Oritani

  4. First Department of Internal Medicine, Faculty of Medicine, Kyushu University, Higashi-Ku, Fukuoka, Japan

    K Shimoda

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  1. R Muromoto
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  9. T Matsuda
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Correspondence to T Matsuda.

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Muromoto, R., Nakao, K., Watanabe, T. et al. Physical and functional interactions between Daxx and STAT3. Oncogene 25, 2131–2136 (2006). https://doi.org/10.1038/sj.onc.1209235

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