Differential regulation of a cellular gene by human interferon
Two cDNA clones complementary to interferon (IFN)-..gamma.. 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/sub r/ polypeptide in vitro. This mRNA was induced by HuIFN-..gamma.. as well as by HuIFN-..cap alpha../sub 2/ but in different manners: (i) IFN-..gamma.. induced this mRNA >100-fold and this induction was sustained for at least 48 h, whereas IFN-..cap alpha../sub 2/ induced it approx. 10-fold but only transiently. (ii) Cells that were pretreated with IFN-..cap alpha../sub 2/ (18 h) became refractory to induction by IFN-..cap alpha../sub 2/ but responded normally to IFN-..gamma... (iii) Cycloheximide and anisomycin inhibited the induction by IFN-..gamma.. but not by IFN-..cap alpha../sub 2/. As analyzed by nuclear runoff transcription, IFN-..gamma.. 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-..gamma... Southern blot analysis indicated that the C5-4 gene is present in a single copy in the genome. The results demonstrate that IFN-..gamma.. and IFN-..cap alpha.. induced the expression of a common gene through different mechanisms and suggest the involvement of an intermediary mechanism in IFN-..gamma..-mediated transcriptional activation of certain cellular genes.
- Research Organization:
- Memorial Sloan-Kettering Cancer Center, New York, NY (USA)
- OSTI ID:
- 6924813
- Journal Information:
- J. Biol. Chem.; (United States), Vol. 263:1
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
INTERFERON
GENETIC EFFECTS
RECOMBINANT DNA
GENE REGULATION
GENES
MAN
MESSENGER-RNA
PHOSPHORUS 32
ANIMALS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOLOGICAL EFFECTS
DAYS LIVING RADIOISOTOPES
DNA
GROWTH FACTORS
ISOTOPES
LIGHT NUCLEI
LYMPHOKINES
MAMMALS
MITOGENS
NUCLEI
NUCLEIC ACIDS
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
PHOSPHORUS ISOTOPES
PRIMATES
PROTEINS
RADIOISOTOPES
RNA
VERTEBRATES
550201* - Biochemistry- Tracer Techniques