Related Experiment Video
Updated: Aug 14, 2026

Merging Absolute and Relative Quantitative PCR Data to Quantify STAT3 Splice Variant Transcripts
Published on: October 9, 2016
Physical and functional interactions between Daxx and STAT3
R Muromoto1, K Nakao, T Watanabe
1Department of Immunology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo, Hokkaido, Japan.
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.
Insights
Type I interferon (IFN) suppresses interleukin-6/Signal transducer and activator of transcription 3 (STAT3) signaling. A Daxx protein, induced by type I IFN, physically interacts with STAT3 to regulate this suppression.
Area of Science:
- Molecular Biology
- Cellular Signaling
- Immunology
Background:
- Signal transducer and activator of transcription 3 (STAT3) is crucial for interleukin-6 (IL-6) cytokine family signaling, impacting cell proliferation and differentiation.
- Dysregulated IL-6/STAT3 signaling is implicated in autoimmune diseases and cancer.
- Type I interferon (IFN) exhibits anti-tumor effects by inducing proapoptotic genes.
Purpose of the Study:
- To investigate the mechanism by which type I IFN suppresses IL-6/STAT3 signaling.
- To determine the role of the type I IFN-induced protein Daxx in this suppressive pathway.
Main Methods:
- Investigated the effect of type I IFN on IL-6/STAT3-mediated transcription and gene expression.
- Examined the function of Daxx in STAT3 transcriptional activation using overexpression and small-interfering RNA (siRNA).
- Utilized co-immunoprecipitation and nuclear co-localization studies to assess Daxx-STAT3 interaction.
Main Results:
- Type I IFN suppressed IL-6/STAT3-mediated transcription and gene expression.
- Daxx, induced by type I IFN, inhibited STAT3 transcriptional activation.
- Reduction of Daxx expression enhanced IL-6/leukemia inhibitory factor (LIF)-induced STAT3-dependent transcription.
- Daxx physically interacted with STAT3 and co-localized in the nucleus.
Conclusions:
- Daxx plays a significant role in mediating type I IFN's suppression of the IL-6/STAT3 signaling pathway.
- Daxx acts as a transcriptional regulator, linking type I IFN signaling to the inhibition of IL-6/STAT3 activity.
Related Concept Videos
The JAK-STAT Signaling Pathway
Assembly of Signaling Complexes
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
TGF - β Signaling Pathway
Intracellular Signaling Affects Focal Adhesions
Some...
Amplifying Signals via Enzymatic Cascade
Master Transcription Regulators
