Expression of the jun-B gene during induction of monocytic differentiation.
The AP-1 protein complex binds to specific DNA sequences that regulate transcription of genes responsive to certain growth factors and phorbol esters. This complex is composed of products of the jun and fos gene families. The present studies have examined the effects of 12-O-tetradecanoylphorbol-13-acetate (TPA) on the regulation of jun-B gene expression during induction of monocytic differentiation. Low levels of jun-B transcripts were present in uninduced HL-60 promyelocytic leukemia cells. In contrast, treatment with TPA was associated with rapid increases in jun-B mRNA levels that were maximal at 3 h and remained elevated at 48 h. The induction of jun-B expression by TPA in these cells preceded that of the c-jun and c-fos genes. Similar increases in jun-B transcripts were detectable in TPA-treated THP-1 and U-937 myeloid leukemia cells, although expression of this gene was transient in the more differentiated THP-1 cells. Run-on assays demonstrated low levels of jun-B gene activation in untreated HL-60 cells, whereas TPA treatment was associated with a 6-fold increase in the transcription rate of this gene. This induction of jun-B expression occurred in the absence of de novo protein synthesis. In contrast, inhibition of protein synthesis was associated with superinduction of TPA-induced jun-B mRNA levels and an increase in stability of this transcript. These findings suggest that jun-B gene expression is regulated at both the transcriptional and posttranscriptional levels during induction of monocytic differentiation.(ABSTRACT TRUNCATED AT 250 WORDS)
Datta
R
R
Laboratory of Clinical Pharmacology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115.
Sherman
M L
ML
Stone
R M
RM
Kufe
D
D
D054713:Bryostatins; D002117:Calcitriol / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D004268:DNA-Binding Proteins / Q000096:biosynthesis*; D015870:Gene Expression / Q000502:physiology; D006801:Humans; D007783:Lactones / Q000494:pharmacology; D007951:Leukemia, Myeloid / Q000235:genetics; D018942:Macrolides; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D016755:Proto-Oncogene Proteins c-jun; D011519:Proto-Oncogenes / Q000235:genetics*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects
D054713:Bryostatins; D004268:DNA-Binding Proteins; D007783:Lactones; D018942:Macrolides; D016755:Proto-Oncogene Proteins c-jun; C046785:bryostatin 1; D002117:Calcitriol; D013755:Tetradecanoylphorbol Acetate