Kb. Andersson et al., CYCLIC-AMP DOWN-REGULATES C-MYC EXPRESSION BY INHIBITION OF TRANSCRIPT INITIATION IN HUMAN B-PRECURSOR REH CELLS, FEBS letters, 337(1), 1994, pp. 71-76
In the human pre-B cell line Reh, activation of the cyclic AMP signal
transduction pathway induces a rapid, transient 10-fold down-regulatio
n of steady-state c-myc mRNA. We have investigated the mechanisms invo
lved in this cAMP-mediated regulation of c-myc expression. Forskolin d
id not alter c-myc mRNA stability. Initiation of c-myc transcripts was
strongly inhibited after 1 h of forskolin treatment, as measured by n
uclear 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 downregu
lates c-myc expression by inhibition of transcriptional initiation.