Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.7.48 (transcriptase)
 9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We reported previously that murine L-929 cells expressing a human interferon (IFN)-gamma cDNA lacking a signal peptide sequence synthesize but fail to secrete human IFN-gamma and support viral replication at a reduced level. These cells also had elevated levels of IFN-inducible gene products. We show here that a similar response is seen in human cells expressing a mutated murine IFN-gamma cDNA. The ability of human IFN-gamma to induce gene expression in murine cells is shown to be due to the intracellular IFN-gamma rather than to clonal variation, induction of endogenous murine IFN, or alternative mediators of antiviral activity. We have used a murine cell line, Ltk-aprt-, which is resistant to both type I and II IFNs but responsive to combined treatment with both. Ltk-aprt- cells transfected with human IFN-gamma cDNA lacking a signal sequence support virus replication at the same level as control cells. However, unlike transfectants containing only the neoR selection gene, clones expressing the mutated human IFN-gamma gene show strong protection against viral infection and elevated levels of 2,5 A synthetase mRNA and MHC class I protein after treatment with IFN-beta alone. Reverse transcriptase-PCR rules out the induction of endogenous murine IFN expression as a mediator of these effects. Thus, expression of intracellular human IFN-gamma mimics treatment with extracellular murine IFN-gamma in permitting a synergistic response to IFN-beta. Given the inability of human IFN-gamma to bind to the murine cell-surface receptor our results show that intracellular IFN-gamma can activate certain responses independent of cell-surface binding.
 ...
PMID:Induction of gene expression by intracellular interferon-gamma: abrogation of the species specificity barrier. 757 13