What question did this study set out to answer?

To investigate whether alpha-interferon activates guanylate-binding protein gene transcription through distinct promoter elements and divergent intracellular signal transduction pathways.

October 1, 1991Molecular and Cellular BiologyOpen Access

Two distinct alpha-interferon-dependent signal transduction pathways may contribute to activation of transcription of the guanylate-binding protein gene.

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Population

In vitro models studying the guanylate-binding protein (GBP) gene promoter

Design

Preclinical

Authors

TDThomas DeckerMax Perutz Labs DLD J LewUniversity of California, San Diego JDJames DarnellRockefeller University

Discussion

Member takes

Implication

Does not yet inform clinical IFN use; leaves open selective pathway targeting in cardiovascular research.

Key Points

To investigate whether alpha-interferon activates guanylate-binding protein gene transcription through distinct promoter elements and divergent intracellular signal transduction pathways.
Assessed transcription activation mediated by the interferon stimulation response element and the IFN-gamma activation site within the guanylate-binding protein promoter.
Characterized the activation kinetics and requirements of DNA-binding factors using protein kinase inhibitors and protein synthesis inhibitors.
Demonstrated that the IFN-gamma activation site is an in vivo responsive element for alpha-interferon, which rapidly activates an IFN-alpha activation factor.
Distinguished the activation mechanisms of ISGF-3, GAF, and AAF using specific kinase and synthesis inhibitors, confirming alpha-interferon receptor binding triggers two separate intracellular signaling pathways.

Structured PICO

Population

In vitro models studying the guanylate-binding protein (GBP) gene promoter

Intervention

Alpha-interferon (IFN-alpha) and gamma-interferon (IFN-gamma)

Outcome

Activation of DNA-binding proteins (ISGF-3, GAF, AAF) and transcription of the GBP genesurrogate

Demonstrates that alpha-interferon activates transcription of the GBP gene via two distinct signal transduction pathways involving different DNA-binding proteins.

Cite This Study

Decker et al. (1991) studied this question.

synapsesocial.com/papers/6a70ea892163a0a01bc51e6e https://doi.org/10.1128/mcb.11.10.5147

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Two distinct alpha-interferon-dependent signal transduction pathways may contribute to activation of transcription of the guanylate-binding protein gene.

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Two distinct alpha-interferon-dependent signal transduction pathways may contribute to activation of transcription of the guanylate-binding protein gene.

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

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