Cyclic AMP downregulates c‐myc expression by inhibition of transcript initiation in human B‐precursor Reh cells

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Abstract
In the human pre‐B cell line Reh, activation of the cyclic AMP signal transduction pathway induces a rapid, transient 10‐fold down‐regulation of steady‐state c‐myc mRNA. We have investigated the mechanisms involved in this cAMP‐mediated regulation of c‐myc expression. Forskolin did not alter c‐myc mRNA stability. Initiation of c‐myc transcripts was strongly inhibited after 1 h of forskolin treatment, as measured by nuclear run‐on assays. Reinitiation of c‐myc transcription was apparent after 3–4 h, and full transcriptional elongation was detected after 8 h of forskolin treatment. These data suggest that cyclic AMP downregulates c‐myc expression by inhibition of transcriptional initiation.