Transcriptionally active Stat1 is required for the antiproliferative effects of both interferon α and interferon γ Journal Article
| Authors: | Bromberg, J. F.; Horvath, C. M.; Wen, Z.; Schreiber, R. D.; Darnell, J. E. Jr |
| Article Title: | Transcriptionally active Stat1 is required for the antiproliferative effects of both interferon α and interferon γ |
| Abstract: | Type I (α, β) and type II (γ) interferons (IFNs) can restrict the growth of many cell types. INF-stimulated gene transcription, a key early event in IFN response, acts through the Janus kinase-signal transducers and activators of transcription pathway, in which both IFN-α and IFN-γ activate the transcription factor Stat1. A cell line lacking Stat1 (U3A) was not growth-arrested by IFN-α or IFN-γ, and experiments were carried out with U3A cells permanently expressing normal or various mutant forms of Stat1 protein. Only cells in which complete Stat1 activity was available (Stat1α) were growth-inhibited by IFN-γ. A mutant that supports 20-30% normal transcription did not cause growth restraint. In contrast, IFN-α growth restraint was imposed by cells producing Stat1β, which lacks transcriptional activation potential. This parallels earlier results showing the truncated Stat1 can function in IFN-α gene activation. In addition to experiments on long-term cultured cells, we also found that wild-type primary mouse embryonic fibroblasts were inhibited by IFNs, but fibroblasts from Stat1- deficient mouse embryos were not inhibited by IFNs. |
| Keywords: | signal transduction; human cell; dna-binding proteins; dose response; nonhuman; alpha interferon; dna synthesis; animal cell; mouse; animals; mice; gene; cells, cultured; cell division; cell growth; embryo; cell line; protein; transcription factor; genetic transcription; transcription, genetic; animalia; gene activation; blotting, western; dna; kinetics; gamma interferon; cell culture; protein-serine-threonine kinases; immunoprecipitation; immunoblotting; fibroblast; fibroblasts; stat3 transcription factor; trans-activators; cyclin-dependent kinases; phosphotransferase; thymidine; interferon-alpha; growth inhibition; growth arrest; cyclin-dependent kinase 2; interferon type ii; stat1 transcription factor; cdc2-cdc28 kinases; interferons; humans; human; priority journal; article; protamine kinase; signal transducers and activators of transcription; janus |
| Journal Title: | Proceedings of the National Academy of Sciences of the United States of America |
| Volume: | 93 |
| Issue: | 15 |
| ISSN: | 0027-8424 |
| Publisher: | National Academy of Sciences |
| Date Published: | 1996-07-23 |
| Start Page: | 7673 |
| End Page: | 7678 |
| Language: | English |
| DOI: | 10.1073/pnas.93.15.7673 |
| PUBMED: | 8755534 |
| PROVIDER: | scopus |
| PMCID: | PMC38805 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 22 November 2017 -- Source: Scopus |
