Lindvall L, Lantz M, Persson A M, Olsson I, Gullberg U
Department of Medicine, University of Lund, Sweden.
Lymphokine Cytokine Res. 1993 Aug;12(4):205-12.
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.
已鉴定出两种分别约为55 kDa（TNF-R55）和75 kDa（TNF-R75）的肿瘤坏死因子（TNF）受体。在早幼粒细胞HL-60细胞中研究了二丁酰环磷腺苷（dbcAMP）激活蛋白激酶A以及佛波酯肉豆蔻酸酯（PMA）激活蛋白激酶C对这两种受体转录和转录后调控的作用。用dbcAMP或腺苷酸环化酶激动剂福斯可林孵育会导致TNF-R75 mRNA水平升高，而TNF-R55 mRNA不受影响。用放线菌素D抑制转录后，通过mRNA的消失判断，TNF-R55和TNF-R75转录本的半衰期均未受影响。因此，蛋白激酶A的激活似乎增强了TNF-R75基因的转录。这种增强不依赖于从头合成蛋白质。用PMA孵育不影响任何一种TNF受体的mRNA水平。用蛋白质合成抑制剂环己酰亚胺孵育后，TNF-R55和TNF-R75 mRNA的半衰期均延长，表明这些基因存在超诱导现象。我们的结果表明，这两种TNF受体在转录水平上可受到不同的调控，并且转录和转录后调控均会发生。
