Cyclic AMP downregulates c-myc expression by inhibition of transcript initiation in human B-precursor Reh cells.
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.
Andersson
K B
KB
Norwegian Radium Hospital, Department of Immunology, Montebello.
Taskén
K
K
Blomhoff
H K
HK
D001402:B-Lymphocytes / Q000378:metabolism*; D015152:Blotting, Northern; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D016259:Genes, myc; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000235:genetics; D006801:Humans; D007700:Kinetics; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
D012333:RNA, Messenger; D005576:Colforsin; D000242:Cyclic AMP; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases