Nuclear integration of JAK/STAT and Ras/AP-1 signaling by CBP and p300.

We report that interferon gamma (IFN-gamma) inhibits transcription of the macrophage scavenger receptor gene by antagonizing the Ras-dependent activities of AP-1 and cooperating ets domain transcription factors, apparently as a result of competition between AP-1/ets factors and activated STAT1 for limiting amounts of CBP and p300. Consistent with this model, ...
STAT1 alpha interacts directly with CBP in cells, and microinjection of anti-CBP and anti-p300 antibodies blocks transcriptional responses to IFN-gamma. Cells lacking STAT1 fail to inhibit AP-1/ets activity, and overexpression of CBP both potentiates IFN-gamma-dependent transcription and relieves AP-1/ets repression. Thus, CBP and p300 integrate both positive and negative effects of IFN-gamma on gene expression by serving as essential coactivators of STAT1 alpha, modulating gene-specific responses to simultaneous activation of two or more signal transduction pathways.
Mesh Terms:
Acetyltransferases, Animals, CREB-Binding Protein, Cell Cycle Proteins, DNA-Binding Proteins, Drug Antagonism, Histone Acetyltransferases, Humans, Interferon-gamma, Macrophage Colony-Stimulating Factor, Macrophages, Membrane Proteins, Mice, Mice, Transgenic, Nuclear Proteins, Receptors, Immunologic, Receptors, Lipoprotein, Receptors, Scavenger, STAT1 Transcription Factor, Scavenger Receptors, Class B, Signal Transduction, Trans-Activators, Transcription Factor AP-1, Transcription Factors, Transcription, Genetic, p300-CBP Transcription Factors
Proc. Natl. Acad. Sci. U.S.A.
Date: Feb. 18, 1997
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