Antiviral response in cells containing Stat1 with heterologous transactivation domains.

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.