Journal ArticleDOI
Jak-STAT pathways and transcriptional activation in response to IFNs and other extracellular signaling proteins
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TLDR
A previously unrecognized direct signal transduction pathway to the nucleus has been uncovered: IFN-receptor interaction at the cell surface leads to the activation of kinases of the Jak family that phosphorylate substrate proteins called STATs (signal transducers and activators of transcription).Abstract:
Through the study of transcriptional activation in response to interferon alpha (IFN-alpha) and interferon gamma (IFN-gamma), a previously unrecognized direct signal transduction pathway to the nucleus has been uncovered: IFN-receptor interaction at the cell surface leads to the activation of kinases of the Jak family that then phosphorylate substrate proteins called STATs (signal transducers and activators of transcription). The phosphorylated STAT proteins move to the nucleus, bind specific DNA elements, and direct transcription. Recognition of the molecules involved in the IFN-alpha and IFN-gamma pathway has led to discoveries that a number of STAT family members exist and that other polypeptide ligands also use the Jak-STAT molecules in signal transduction.read more
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References
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Journal ArticleDOI
Purification and cloning of interferon-stimulated gene factor 2 (ISGF2): ISGF2 (IRF-1) can bind to the promoters of both beta interferon- and interferon-stimulated genes but is not a primary transcriptional activator of either.
TL;DR: Interferon-stimulated gene factor 2 (ISGF2) was purified from HeLa cells treated with alpha interferon and sequence analysis revealed that the ISGF2 protein was the same as that encoded by the cDNA clone IRF-1, which has been claimed to activate transcription ofinterferon genes.
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Interferon-alpha regulates nuclear translocation and DNA-binding affinity of ISGF3, a multimeric transcriptional activator.
TL;DR: It is shown that post-translational activation of ISGF3 in the cytoplasm of IFN-alpha-treated cells requires two cy toplasmic activities to produce an ISRE-binding complex that accumulates in the nucleus, and that these activities are actually distinct subunits of the IS GF3 complex, which associate through noncovalent interaction.
Journal ArticleDOI
Overlapping elements in the guanylate-binding protein gene promoter mediate transcriptional induction by alpha and gamma interferons.
TL;DR: Two different elements were required to obtain the maximal response of the GBP gene to IFN-gamma: theIFN-alpha-stimulated response element and an overlapping element termed the IFN -gamma activation site.
Journal ArticleDOI
A novel interferon-inducible domain: structural and functional analysis of the human interferon regulatory factor 1 gene promoter.
TL;DR: Cloned and functionally characterized the human interferon regulatory factor 1 (IRF-1) gene promoter and showed that IFN inducibility is conferred by a novel imperfect inverted-repeat arrangement of two GAAANN motifs within a domain, 130 nucleotides upstream of transcription initiation.
Journal ArticleDOI
Identification and sequence of an accessory factor required for activation of the human interferon γ receptor
Jaemog Soh,Robert J. Donnelly,Serguei V. Kotenko,Thomas M. Mariano,Jeffry R. Cook,Ning Wang,Stuart L. Emanuel,Barbara Schwartz,Toru Miki,Sidney Pestka +9 more
TL;DR: It is confirmed that an additional factor encoded on human chromosome 21 is required for reconstitution of antiviral activity against EMCV, and that this accessory factor belongs to a family of such accessory factors responsible for different actions of IFN-γ.
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