Stat1-independent regulation of gene expression in response to IFN-γ

Chilakamarti V. Ramana, M. Pilar Gil, Yulong Han, Richard M. Ransohoff, Robert D. Schreiber, George R. Stark

Research output: Contribution to journalArticle

200 Scopus citations

Abstract

Although Stat1 is essential for cells to respond fully to IFN-γ, there is substantial evidence that, in the absence of Stat1, IFN-γ can still regulate the expression of some genes, induce an antiviral state and affect cell growth. We have now identified many genes that are regulated by IFN-γ in serum-starved Stat1-null mouse fibroblasts. The proteins induced by IFN-γ in Stat1-null cells can account for the substantial biological responses that remain. Some genes are induced in both wild-type and Stat1-null cells and thus are truly Stat1-independent. Others are subject to more complex regulation in response to IFN-γ, repressed by Stat1 in wild-type cells and activated in Stat1-null cells. Many genes induced by IFN-γ in Stat1-null fibroblasts also are induced by platelet-derived growth factor in wild-type cells and thus are likely to be involved in cell proliferation. In mouse cells expressing the docking site mutant Y440F of human IFN-γ receptor subunit 1, the mouse Stat1 is not phosphorylated in response to human IFN-γ, but c-myc and c-jun are still induced, showing that the Stat1 docking site is not required for Stat1-independent signaling.

Original languageEnglish
Pages (from-to)6674-6679
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume98
Issue number12
DOIs
StatePublished - Jun 5 2001

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