Regulation of jun-B expression by a cyclic AMP (cAMP)-dependent mechanism in human myeloid cells.
The present studies have examined the regulation of the jun-B early response gene by cyclic AMP (cAMP)-dependent signaling pathways. The 2.0-kb jun-B transcript was at low but detectable levels in uninduced human HL-60 myeloid leukemia cells. In contrast, treatment with 1 mmol/L8-bromo-adenosine 3',5'-cyclic monophosphate (8-Br-cAMP) in the presence of isobutylmethylxanthine, an inhibitor of cAMP-dependent phosphodiesterase, was associated with increases in jun-B transcripts that were maximal by 1 hour and then decreased to near pretreatment levels by 6 hours. Similar findings were obtained with 8-(4-chlorophenylthio)-adenosine 3',5'-cyclic monophosphate (8-CPT-cAMP) and N6,2'-0-dibutyryladenosine 3',5'-cyclic monophosphate (dBt-cAMP). jun-B transcripts were also increased with other agents that increase intracellular cAMP levels, such as prostaglandin E2 (PGE2) and forskolin. Moreover, inhibition of cAMP-dependent protein kinase by the isoquinolinesulfonamide H-8 blocked 8-Br-cAMP-induced increases in jun-B expression. The results of nuclear run-on assays demonstrate that treatment of HL-60 cells with PGE2, forskolin, 8-Br-cAMP, and dBt-cAMP is associated with increases in the rate of jun-B transcription. The present findings also demonstrate that the related jun-D gene is similarly regulated by a cAMP-dependent pathway. Taken together, these findings suggest that stimulation of cAMP-dependent protein kinase is involved in the induction of jun gene expression in myeloid leukemia cells.
Datta
R
R
Laboratory of Clinical Pharmacology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115.
Nakamura
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T
Sherman
M L
ML
Kufe
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D
D001853:Bone Marrow / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D000242:Cyclic AMP / Q000494:pharmacology*; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects*; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000378:metabolism* / Q000473:pathology; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D014157:Transcription Factors; D000242:Cyclic AMP