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Antiviral response in cells containing Stat1 with heterologous transactivation domains
1Laboratory of Molecular Cell Biology, The Rockefeller University, New York, New York 10021, USA.
Abstract:
The STATs (signal transducers and activators of transcription), latent cytoplasmic transcription factors, are activated by binding of extracellular polypeptides to cell surface receptors. Dimerization, accumulation in the nucleus, and transcriptional inductions of specific genes then occur. The COOH terminus of the STATs acts as a transcriptional activation domain (TAD). Stat1, one of seven mammalian STAT genes, forms a homodimer after activation by gamma interferon and induces transcription of a number of genes. These induced genes in turn produce the antiviral state. In the present experiments we used a Stat1-deficient cell line complemented with Stat1 or various fusion constructs in which the wild-type Stat1 TAD was replaced by other TADs to test the possibility that a specific activating domain was necessary for the induction of the antiviral response. We found that a wide variety of TADs with different activation potential appended to the Stat1 COOH terminus could substitute for the wild-type protein in inducing the antiviral state.
Insights
Signal transducers and activators of transcription (STATs) are crucial for antiviral responses. Researchers found that various transcriptional activation domains (TADs) can substitute for the wild-type Stat1 TAD in inducing this antiviral state.
Area of Science:
- Molecular Biology
- Immunology
- Cell Biology
Background:
- Signal transducers and activators of transcription (STATs) are latent cytoplasmic transcription factors.
- STATs are activated by extracellular signals binding to cell surface receptors, leading to nuclear translocation and gene induction.
- The COOH terminus of STATs functions as a transcriptional activation domain (TAD).
Purpose of the Study:
- To investigate whether a specific TAD is essential for Stat1-mediated antiviral response induction.
- To determine if different TADs can functionally replace the wild-type Stat1 TAD.
Main Methods:
- Utilized a Stat1-deficient cell line.
- Complemented the cell line with wild-type Stat1 or fusion constructs where the Stat1 TAD was replaced by other TADs.
- Assessed the induction of the antiviral state.
Main Results:
- A broad range of TADs, irrespective of their specific activation potential, could functionally substitute for the wild-type Stat1 TAD.
- The antiviral state could be induced even when the Stat1 COOH terminus was replaced by alternative TADs.
Conclusions:
- The specific identity of the TAD is not critical for Stat1-mediated antiviral response.
- The results suggest a degree of functional redundancy among TADs in the context of Stat1 signaling and antiviral immunity.