
pmid: 19422799
The transcription factor ATF-2, a member of the ATF/CREB family, is a target of p38 that are involved in stress-induced apoptosis and in Toll-like receptor (TLR)-mediated signaling. Phosphorylation of ATF-2 at Thr-71 was enhanced by treating of RAW264.7 macrophage cells with either LPS, MALP-2, or CpG-ODN. LPS treatment enhanced the trans-activation capacity of ATF-2. Among multiple LPS-induced genes, the LPS-induced expression of Socs-3 was significantly reduced by the treatment of RAW264.7 cells with an Atf-2 siRNA. Transcription from the Socs-3 promoter was synergistically stimulated by ATF-2 and LPS, whereas it was suppressed by Atf-2 siRNA. Histone deacetylase 1 (HDAC1) interacted with ATF-2 after LPS treatment, but not before treatment. Treatment of RAW264.7 cells with trichostatin A, an inhibitor of HDAC, suppressed the LPS-induced Socs-3 expression, suggesting that HDAC1 positively regulates the LPS-induced transcription of Socs-3. Thus, ATF-2 plays an important role in TLR-mediated transcriptional control in macrophage cells.
Lipopolysaccharides, Activating Transcription Factor 2, Transcription, Genetic, Macrophages, Toll-Like Receptors, Histone Deacetylase 1, Suppressor of Cytokine Signaling Proteins, Hydroxamic Acids, Histone Deacetylases, Cell Line, Histone Deacetylase Inhibitors, Mice, Gene Expression Regulation, Suppressor of Cytokine Signaling 3 Protein, Animals, Phosphorylation, Promoter Regions, Genetic
Lipopolysaccharides, Activating Transcription Factor 2, Transcription, Genetic, Macrophages, Toll-Like Receptors, Histone Deacetylase 1, Suppressor of Cytokine Signaling Proteins, Hydroxamic Acids, Histone Deacetylases, Cell Line, Histone Deacetylase Inhibitors, Mice, Gene Expression Regulation, Suppressor of Cytokine Signaling 3 Protein, Animals, Phosphorylation, Promoter Regions, Genetic
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