Multiple mechanisms regulate c-myc gene expression during normal T cell activation.
Quiescent normal human T cells express low levels of steady-state c-myc mRNA as a result of low constitutive promoter utilization, a block to transcriptional elongation within the gene, and rapid degradation of c-myc mRNA in the cytoplasm. Following the activation of the T cell receptor (TCR)/CD3 complex, quiescent T cells are induced to express c-myc mRNA. Two intracellular pathways, one involving protein kinase C activation and the other mediated by increased intracellular calcium concentration, are activated by TCR/CD3 receptor stimulation. These two pathways, which can be activated by phorbol myristate acetate (PMA) and ionomycin respectively, appear to play complementary roles in the transcriptional induction of c-myc gene expression by the antigen receptor complex. Ionomycin treatment of quiescent cells leads to enhanced c-myc expression primarily as a result of increased transcriptional initiation. In contrast, PMA contributes to c-myc expression, at least in part, by decreasing the block to transcriptional elongation present within the gene. Both the PMA- and ionomycin-mediated induction of c-myc expression can be independently enhanced by stabilization of c-myc mRNA in the cytoplasm. These observations demonstrate that multiple mechanisms co-operate to regulate c-myc gene expression during normal T cell activation.
D000900:Anti-Bacterial Agents / Q000494:pharmacology; D002455:Cell Division; D003432:Cross-Linking Reagents; D003513:Cycloheximide / Q000494:pharmacology; D004987:Ethers / Q000494:pharmacology; D005786:Gene Expression Regulation; D006801:Humans; D007399:Interphase; D015759:Ionomycin; D008213:Lymphocyte Activation; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016271:Proto-Oncogene Proteins c-myc; D011519:Proto-Oncogenes; D012333:RNA, Messenger / Q000096:biosynthesis; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014158:Transcription, Genetic
D000900:Anti-Bacterial Agents; D003432:Cross-Linking Reagents; D004987:Ethers; D011518:Proto-Oncogene Proteins; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell; D015759:Ionomycin; D003513:Cycloheximide; D013755:Tetradecanoylphorbol Acetate