Independent transcriptional and posttranscriptional regulation of the two tumor necrosis factor receptors in promyelocytic HL-60 cells.
Two separate tumor necrosis factor (TNF) receptors of approximately 55 kDa (TNF-R55) and 75 kDa (TNF-R75) have been identified. The role of protein kinase A activation by dibutyryl cAMP (dbcAMP) and of protein kinase C activation with phorbol myristate acetate (PMA) for transcriptional and posttranscriptional regulation of the two receptors was investigated in promyelocytic HL-60 cells. Incubation with dbcAMP or the adenylate cyclase agonist forskolin caused an increase in the level of TNF-R75 mRNA while TNF-R55 mRNA was unaffected. The half-life of transcripts for both TNF-R55 and TNF-R75 was unaffected as judged by disappearance of mRNA after inhibition of transcription with actinomycin D. Thus the transcription of the TNF-R75 gene seemed to be enhanced by activation of protein kinase A. This enhancement was not dependent on de novo protein synthesis. Incubation with PMA did not affect the mRNA level of any of the TNF receptors. Both TNF-R55 and TNF-R75 mRNA showed a prolonged half-life after incubation with the inhibitor of protein synthesis cycloheximide, indicating superinduction of the genes. Our results demonstrate that the two TNF receptors can be regulated differently at the transcriptional level and that both transcriptional and posttranscriptional regulation occurs.
Lindvall
L
L
Department of Medicine, University of Lund, Sweden.
Lantz
M
M
Persson
A M
AM
Olsson
I
I
Gullberg
U
U
D001483:Base Sequence; D003994:Bucladesine / Q000494:pharmacology; D002462:Cell Membrane / Q000378:metabolism; D005576:Colforsin / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D003513:Cycloheximide / Q000494:pharmacology; D017931:DNA Primers; D004789:Enzyme Activation; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007700:Kinetics; D015473:Leukemia, Promyelocytic, Acute; D008969:Molecular Sequence Data; D016376:Oligonucleotides, Antisense; D016133:Polymerase Chain Reaction; D011493:Protein Kinase C / Q000378:metabolism; D012323:RNA Processing, Post-Transcriptional / Q000187:drug effects; D012333:RNA, Messenger / Q000096:biosynthesis / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000096:biosynthesis*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects; D014407:Tumor Cells, Cultured
D017931:DNA Primers; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D018124:Receptors, Tumor Necrosis Factor; D005576:Colforsin; D003994:Bucladesine; D003513:Cycloheximide; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate