T cell activation signals upregulate CBP-dependent transcriptional activity.
The transcriptional coactivator CREB-binding protein (CBP) is known to play an important role in coupling signal transduction pathways to changes in gene expression. In many cases, this is achieved by the stimulus-specific recruitment of CBP to promoter-bound transcription factors. However, a number of recent studies have suggested that signal transduction pathways can also directly influence CBP-mediated transcriptional activity. Here we show that in Jurkat cells the activity of the CBP C-terminal transactivation domain is strongly upregulated in response to either T cell receptor stimulation or the combination of ionomycin and phorbol ester. We further show that maximal stimulation of CBP-mediated transcription requires the synergistic activation of both the calcineurin and Ras-MAPK signaling pathways. These results indicate that CBP can function as a T cell activation-inducible transcriptional coactivator and is therefore likely to play an important role in T cell activation-induced gene expression.
Department of Microbiology-Immunology, Northwestern University Medical School, Chicago, Illinois 60611, USA.
P S
PS
Riggins
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Clipstone
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017252:CD3 Complex / Q000276:immunology; D050882:CREB-Binding Protein; D019703:Calcineurin / Q000378:metabolism; D065095:Calcineurin Inhibitors; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D004274:DNA, Recombinant; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D015759:Ionomycin / Q000494:pharmacology; D007476:Ionophores / Q000494:pharmacology; D019169:Jurkat Cells; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology*; D010957:Plasmids / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism*; D016559:Tacrolimus / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D015534:Trans-Activators / Q000235:genetics / Q000502:physiology*; D014158:Transcription, Genetic; D014162:Transfection; D015854:Up-Regulation
D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D065095:Calcineurin Inhibitors; D004274:DNA, Recombinant; D004791:Enzyme Inhibitors; D005419:Flavonoids; D007476:Ionophores; D009687:Nuclear Proteins; D011993:Recombinant Fusion Proteins; D015534:Trans-Activators; D015759:Ionomycin; D008156:Luciferases; D050882:CREB-Binding Protein; C494363:CREBBP protein, human; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D019703:Calcineurin; D013755:Tetradecanoylphorbol Acetate; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; D016559:Tacrolimus