Abstract
Stimulation of the cAMP-dependent signaling pathway exerts an inhibitory effect on the proliferation and effector functions of T cells. The ability of T cells to form high intracellular levels of cAMP is acquired during development in the human thymus and is retained by the majority of mature peripheral T lymphocytes. Here we show that elevated cAMP levels in T cells correlate with the expression of the potent transcriptional repressor ICER (inducible cAMP early repressor) previously described in the hypothalamic-pituitary-gonadal axis. Further, in transcriptional assays in vivo, ICER inhibits calcineurin-mediated expression of the interleukin 2 promoter as well as Tax-mediated transactivation of the human T-lymphotropic virus type I (HTLV-I) promoter. Thus, the induction of ICER in T cells may play an important role in the cAMP-induced quiescence and the persistent latency of HTLV-I.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Base Sequence
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Calcineurin
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Calmodulin-Binding Proteins / metabolism
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Cell Differentiation
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Child, Preschool
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Conserved Sequence
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Cyclic AMP / pharmacology*
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Cyclic AMP Response Element Modulator
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DNA Primers / genetics
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DNA, Complementary / genetics
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DNA-Binding Proteins / biosynthesis*
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DNA-Binding Proteins / genetics
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Genes, pX
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Human T-lymphotropic virus 1 / genetics
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Humans
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In Vitro Techniques
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Infant
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Interleukin-2 / genetics
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Molecular Sequence Data
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Phosphoprotein Phosphatases / metabolism
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Promoter Regions, Genetic
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Repressor Proteins / biosynthesis*
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Repressor Proteins / genetics
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Signal Transduction
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T-Lymphocytes / cytology
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T-Lymphocytes / drug effects*
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T-Lymphocytes / metabolism*
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Transcriptional Activation
Substances
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Calmodulin-Binding Proteins
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DNA Primers
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DNA, Complementary
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DNA-Binding Proteins
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Interleukin-2
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Repressor Proteins
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Cyclic AMP Response Element Modulator
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Cyclic AMP
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Calcineurin
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Phosphoprotein Phosphatases