Convergent regulation of NF-IL6 and Oct-1 synthesis by interleukin-6 and retinoic acid signaling in embryonal carcinoma cells.
The nuclear signaling by the pleiotropic cytokine interleukin-6 (IL-6) has been investigated in human embryonal carcinoma cells and T cells. We show that Oct-1, a ubiquitously expressed octamer-binding protein known to be regulated posttranslationally, can also be regulated at the levels of mRNA and protein synthesis by IL-6 and by retinoic acid (RA) in human embryonal carcinoma cells. NF-IL6, an IL-6-inducible transcription factor of the C/EBP family, can confer this regulation and is itself regulated by both signals. The abundance and the molar ratios of the three forms of NF-IL6, corresponding to peptides initiated in frame from different AUGs of the same NF-IL6 mRNA species, are regulated by IL-6 and by RA. These results suggest that the two signal transduction pathways overlap in human embryonal carcinoma cells and that Oct-1 may be downstream of NF-IL6 in the shared regulatory cascade. Enhanced Oct-1 synthesis correlates with one of the functions of Oct-1, i.e., stimulation of adenovirus DNA replication. This provides an example of a possible functional consequence of IL-6 and RA signaling that is mediated by NF-IL6 and Oct-1 regulation.
Hsu
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Brookdale Center for Molecular Biology, Mount Sinai School of Medicine, New York, New York 10029.
Chen-Kiang
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D000260:Adenoviruses, Human / Q000235:genetics; D022762:CCAAT-Enhancer-Binding Proteins; D002454:Cell Differentiation; D004261:DNA Replication; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000502:physiology*; D005786:Gene Expression Regulation; D051863:Host Cell Factor C1; D006801:Humans; D066298:In Vitro Techniques; D015850:Interleukin-6 / Q000502:physiology*; D009687:Nuclear Proteins / Q000096:biosynthesis*; D050811:Octamer Transcription Factor-1; D050814:Octamer Transcription Factor-3; D015398:Signal Transduction; D013724:Teratoma / Q000473:pathology / Q000503:physiopathology; D014157:Transcription Factors / Q000096:biosynthesis* / Q000502:physiology*; D014158:Transcription, Genetic; D014162:Transfection; D014212:Tretinoin / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D014779:Virus Replication
D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; C497692:HCFC1 protein, human; D051863:Host Cell Factor C1; D015850:Interleukin-6; D009687:Nuclear Proteins; D050811:Octamer Transcription Factor-1; D050814:Octamer Transcription Factor-3; C494165:POU2F1 protein, human; C494173:POU5F1 protein, human; D014157:Transcription Factors; D014212:Tretinoin