Transcriptionally active Stat1 is required for the antiproliferative effects of both interferon α and interferon γ

Jacqueline F. Bromberg, Curt M. Horvath, Zilong Wen, Robert D. Schreiber, James E. Darnell*

*Corresponding author for this work

Research output: Contribution to journalArticle

407 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)7673-7678
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume93
Issue number15
DOIs
StatePublished - Jul 23 1996

Keywords

  • growth arrest
  • interferons
  • signal transducers and activators of transcription

ASJC Scopus subject areas

  • General

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