Transcriptional and post-transcriptional regulation of c-jun expression during monocytic differentiation of human myeloid leukemic cells

• Published in: The Journal of biological chemistry Vol. 265; no. 6; pp. 3320 - 3323
• Main Authors: Sherman, M L, Stone, R M, Datta, R, Bernstein, S H, Kufe, D W
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Elsevier Inc 25.02.1990; American Society for Biochemistry and Molecular Biology
• Subjects: Biological and medical sciences; Calcitriol - pharmacology; Cell Differentiation; Cell Line; Cycloheximide - pharmacology; DNA-Binding Proteins - genetics; Fundamental and applied biological sciences. Psychology; Gene expression; Gene Expression Regulation, Neoplastic - drug effects; Humans; Leukemia, Promyelocytic, Acute; Lymphoma, Large B-Cell, Diffuse; Molecular and cellular biology; Molecular genetics; Monocytes - drug effects; Protein-Tyrosine Kinases - genetics; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins c-jun; Proto-Oncogenes; RNA Processing, Post-Transcriptional; Tetradecanoylphorbol Acetate - pharmacology; Transcription Factors - genetics; Transcription, Genetic - drug effects; Human; Northern blotting; Cell culture; Regulation(control); C-Onc gene; Chronic myelocytic leukemia; Cell differentiation; Gene expression
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/S0021-9258(19)39769-8

AP-1, the polypeptide product of c-jun, recognizes and binds to specific DNA sequences and stimulates transcription of genes responsive to certain growth factors and phorbol esters such as 12-O-tetradecanoylphorbol-13-acetate (TPA). We studied the effects of TPA on the regulation of c-jun gene expression in HL-60 cells during monocytic differentiation. Low levels of c-jun transcripts were detectable in untreated HL-60 leukemic cells, increased significantly by 6 h, and reached near maximal levels by 24 h of exposure to 32 nM TPA. Similar kinetics of c-jun induction by TPA were observed in human U-937 and THP-1 monocytic leukemia cells. Similar findings were obtained with bryostatin 1 (10 nM), another activator of protein kinase C and inducer of monocytic differentiation. Furthermore, 1,25-dihydroxyvitamin D3 (0.5 microM), a structurally distinct agent which also induces HL-60 monocytic differentiation, increased c-jun expression. TPA treatment of HL-60 cells in the presence of cycloheximide was associated with superinduction of c-jun transcripts. Run-on analysis demonstrated detectable levels of c-jun gene transcription in untreated HL-60 cells, and that exposure to TPA increases this rate 3.3-fold. Treatment of HL-60 cells with both TPA and cycloheximide had no effect on the rates of c-jun transcription. The half-life of c-jun RNA as determined by treating HL-60 cells with TPA and actinomycin D was 30 min. In contrast, the half-life of c-jun RNA in TPA-treated HL-60 cells exposed to cycloheximide and actinomycin D was greater than 2 h. These findings suggested that the increase in c-jun RNA observed during TPA-induced monocytic differentiation is mediated by both transcriptional and post-transcriptional mechanisms.