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Signal transduction pathway activating interferon-alpha-stimulated gene expression
S A Veals1, D S Kessler, S Josiah
1Department of Pathology, New York University School of Medicine, NY 10016.
British Journal of Haematology
|October 1, 1991
Summary
Interferon-alpha (IFN alpha) triggers cellular responses by activating the ISGF3 transcription factor. This protein complex, assembled from cytoplasmic precursors, translocates to the nucleus, initiating the expression of IFN alpha-stimulated genes.
Area of Science:
- Molecular Biology
- Cellular Biology
- Immunology
Background:
- Interferon-alpha (IFN alpha) induces significant physiological changes in target cells.
- These changes involve antiviral states, inhibited proliferation, and modulated differentiation, all requiring gene transcriptional activation.
Purpose of the Study:
- To characterize the macromolecular components involved in IFN alpha-induced gene expression.
- To define the biochemical mechanism of IFN alpha signal transduction.
Main Methods:
- Identification of the IFN alpha stimulated response element (ISRE) in gene promoters.
- Characterization of the transcription factor ISGF3 and its activation pathway.
Main Results:
- ISRE is a 15 bp element necessary and sufficient for transcriptional activation of IFN alpha-stimulated genes (ISGs).
- ISGF3, a transcription factor, binds to ISRE and mediates ISG induction.
- Active ISGF3 is formed in cells exposed to IFN alpha through assembly and nuclear translocation of cytoplasmic precursors.
Conclusions:
- ISGF3 assembly and nuclear translocation represent the earliest defined event in the IFN alpha response pathway.
- Understanding this pathway is crucial for elucidating IFN alpha's biological effects.