Complex regulation of the T cell receptor alpha gene: three different modes of triggering induction.
The T cell receptor (TcR) for antigen is composed of variable alpha and beta subunits in noncovalent association with the invariant T3 multimer. TcR/T3 transcripts accumulate in a specific sequence during T cell development; TcR alpha transcripts are the last in the series to accumulate. To explore the regulation of TcR alpha gene expression, we investigated a T lymphoma cell clone which constitutively expresses TcR beta, T3 delta and T3 epsilon mRNA, but essentially lacks detectable TcR alpha mRNA. The cell clone can be induced to accumulate substantial amounts of TcR alpha mRNA in response to phorbol myristate acetate (PMA) or calcium ionophore A23187. Two different protein synthesis inhibitors also induce TcR alpha mRNA. The following evidence indicates that PMA, A23187 and cycloheximide induce TcR alpha by different mechanisms: (a) treatment with a combination of two agents induces greater than additive amounts of TcR alpha mRNA than that induced by a single agent; (b) the immunosuppressant cyclosporin A specifically inhibits A23187-mediated TcR alpha mRNA induction, whereas it fails to inhibit PMA or cycloheximide-mediated induction; and (c) both A23187 and PMA increase the rate of TcR alpha gene transcription, while cycloheximide influences TcR alpha mRNA accumulation by post-transcriptional mechanisms.
D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002460:Cell Line; D003524:Cyclosporins / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D051379:Mice; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012323:RNA Processing, Post-Transcriptional / Q000187:drug effects; D012333:RNA, Messenger / Q000096:biosynthesis; D011948:Receptors, Antigen, T-Cell / Q000187:drug effects / Q000235:genetics*; D013601:T-Lymphocytes / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D003524:Cyclosporins; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell; D000001:Calcimycin; D013755:Tetradecanoylphorbol Acetate