Convergent regulation of NF-IL6 and Oct-1 synthesis by interleukin-6 and retinoic acid signaling in embryonal carcinoma cells

Abstract

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.