Transcriptional regulation of interferon-responsive genes is closely linked to interferon receptor occupancy.

Open Access
Publisher Website
Google Scholar
Abstract
We show that human glioblastoma cells, moving from exponential growth into a state of density‐dependent growth arrest, demonstrate a 7‐fold drop in the total number of alpha‐IFN‐receptors expressed per cell. This loss of receptor activity was not seen when cells were grown in the presence of anti‐alpha‐IFN‐monoclonal antibody. The active binding sites expressed on the arrested cell population were of reduced affinity for IFN, relative to the high‐affinity sites expressed on the growing cells, resulting in a 3‐fold lower initial rate of IFN‐binding to the arrested cells. We exploited this difference to investigate the relationship between IFN receptor binding and induced gene transcription. As determined by nuclear run‐off assays, the transcriptional response of both the gene family 1‐8 and 2‐5A synthetase to IFN treatment also showed a 3‐fold reduction in density‐arrested cells. Longer‐term (0‐8 h) induction and down‐regulation of gene transcription in IFN‐treated cells closely followed the binding to, and down‐regulation of, cell surface‐localized IFN receptors. Furthermore, inhibition of the intracellular breakdown of IFN did not affect transcriptional responses to IFN. Thus transcription of these IFN‐induced genes is closely linked to surface receptor occupancy and is most likely mediated by transmembrane signals alone.