Regulation of jun-B expression by a cyclic AMP (cAMP)-dependent mechanism
in human myeloid cells
R Datta, T Nakamura, ML Sherman and D Kufe
Laboratory of Clinical Pharmacology, Dana-Farber Cancer Institute, Harvard
Medical School, Boston, MA 02115.
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.
Volume 78,
Issue 1,
pp. 83-88,
07/01/1991
Copyright © 1991 by The American Society of Hematology
