cAMP inducibility of transcriptional repressor ICER in developing and mature human T lymphocytes.
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.
Bodor
J
J
Laboratory of Molecular Endocrinology, Massachusetts General Hospital, Boston, MA 02114, USA.
Spetz
A L
AL
Strominger
J L
JL
Habener
J F
JF
D000595:Amino Acid Sequence; D001483:Base Sequence; D019703:Calcineurin; D002148:Calmodulin-Binding Proteins / Q000378:metabolism; D002454:Cell Differentiation; D002675:Child, Preschool; D017124:Conserved Sequence; D000242:Cyclic AMP / Q000494:pharmacology*; D051786:Cyclic AMP Response Element Modulator; D017931:DNA Primers / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D016355:Genes, pX; D015368:Human T-lymphotropic virus 1 / Q000235:genetics; D006801:Humans; D066298:In Vitro Techniques; D007223:Infant; D007376:Interleukin-2 / Q000235:genetics; D008969:Molecular Sequence Data; D010749:Phosphoprotein Phosphatases / Q000378:metabolism; D011401:Promoter Regions, Genetic; D012097:Repressor Proteins / Q000096:biosynthesis* / Q000235:genetics; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D015533:Transcriptional Activation
D002148:Calmodulin-Binding Proteins; D017931:DNA Primers; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D007376:Interleukin-2; D012097:Repressor Proteins; D051786:Cyclic AMP Response Element Modulator; D000242:Cyclic AMP; D019703:Calcineurin; D010749:Phosphoprotein Phosphatases