Differential regulation of a cellular gene by human interferon-γ and interferon-α Journal Article
| Authors: | Caplen, H. S.; Gupta, S. L. |
| Article Title: | Differential regulation of a cellular gene by human interferon-γ and interferon-α |
| Abstract: | Two cDNA clones complementary to interferon (IFN)-γ-inducible mRNAs in human cells were isolated, and one of these, C5-4, was used for studying the regulation of its cognate mRNA by IFNs. C5-4 cDNA hybridized to a 2.2-kilobase mRNA that coded for a 42,000 M(r) polypeptide in vitro. This mRNA was induced by HuIFN-γ as well as by HuIFN-α2 but in different manners: (i) IFN-γ induced this mRNA > 100-fold and this induction was sustained for at least 48 h, whereas IFN-α2 induced it ~10-fold but only transiently. (ii) Cells that were pretreated with IFN-α2 (18 h) became refractory to induction by IFN-α2 but responded normally to IFN-γ. (iii) Cycloheximide (50 μg/ml) and anisomycin (10 μm or higher) inhibited the induction by IFN-γ but not by IFN-α2, suggesting the requirement for some newly synthesized, presumably IFN-γ-induced, protein factor(s) in IFN-γ-mediated but not in IFN-α2-mediated induction. Interestingly, this inhibition by cycloheximide of the IFN-γ-mediated inhibition was overcome by 24 h, whereas a sustained inhibition was obtained with anisomycin. Our results suggest that this release from cycloheximide-mediated inhibition was apparently due to a leakiness in its inhibitory action on protein biosynthesis. As analyzed by nuclear runoff transcription, IFN-γ induced the transcription of C5-4-specific RNA within 2 h and it was inhibited by cycloheximide, indicating that the newly synthesized protein mediator(s) required plays a role in the transcriptional activation of the C5-4 gene by IFN-γ. Southern blot analysis indicated that the C5-4 gene is present in a single copy in the genome. The results demonstrate that IFN-γ and IFN-α induced the expression of a common gene through different mechanisms and suggest the involvement of an intermediary mechanism in IFN-γ-mediated transcriptional activation of certain cellular genes. |
| Keywords: | human cell; alpha interferon; genetic transcription; transcription, genetic; gene expression regulation; cloning, molecular; dna; kinetics; gamma interferon; cell culture; rna, messenger; nucleic acid hybridization; complementary dna; genetic regulation; interferon type i; cycloheximide; interferon type ii; anisomycin; human; support, non-u.s. gov't; support, u.s. gov't, p.h.s.; genes, structural |
| Journal Title: | Journal of Biological Chemistry |
| Volume: | 263 |
| Issue: | 1 |
| ISSN: | 0021-9258 |
| Publisher: | American Society for Biochemistry and Molecular Biology |
| Date Published: | 1988-01-05 |
| Start Page: | 332 |
| End Page: | 339 |
| Language: | English |
| PUBMED: | 3121611 |
| PROVIDER: | scopus |
| DOI: | 10.1016/S0021-9258(19)57397-5 |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
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