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TRADD interacts with STAT1-α and influences interferon-γ signaling

  • A Corrigendum to this article was published on 01 March 2004
  • An Erratum to this article was published on 01 March 2004

Abstract

Tumor necrosis factor receptor 1 (TNFR1)-associated death domain protein (TRADD) is essential in recruiting signaling molecules to the TNFR1 receptor complex. Interferon-γ (IFN-γ) is a potent activator of macrophages and uses signal transducer and activator of transcription 1-α (STAT1-α) for signal transduction. Here we demonstrate that IFN-γ induces the formation of a nuclear-localized TRADD–STAT1-α complex. IFN-γ-mediated STAT1-α phosphorylation was prolonged in cells with reduced TRADD expression. Moreover, we noted an increase in IFN-γ-mediated STAT1-α DNA-binding activity, nuclear presence and transcriptional potential in the TRADD knockdown cells. These data indicate that TRADD may be involved in IFN-γ signaling by forming a complex with STAT1-α within the nucleus and regulating IFN-γ-mediated STAT1-α activation.

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Acknowledgements

We thank Z.D. Ma and R. Shah for assistance with the ChIP assay; C. Wilson for assistance with RPA analysis; and S. Frank for comments on the manuscript. The TRADD expression construct was a gift from H. Wu. Supported in part by National Institutes of Health grants NS-36765 and NS-39954 (E.N.B.), and the Medical Scientist Training Program at The University of Alabama at Birmingham and National Institutes of Health Predoctoral Fellowships T32 AI-07051-26 and F30 NS-47051 (D.R.W.).

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Competing interests

The authors declare no competing financial interests.

Correspondence to Etty N Benveniste.

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Figure 1: IFN-γ treatment induces TRADD–STAT1-α complex formation.
Figure 2: TRADD and STAT1-α colocalize to the nucleus.
Figure 3: TRADD translocation is independent of STAT1-α activation.
Figure 4: The TRADD N terminus binds STAT1-α.
Figure 5: TRADD affects IFN-γ-mediated STAT1-α activation.
Figure 6: TRADD affects STAT1-α transcriptional activity.
Figure 7: TRADD involvement in IFN-γ-regulated genes.