Human PKR Transfected into Murine Cells Stimulates Expression of Genes under Control of the HIV1 or HTLV-I LTR

Eliane F. Meurs, Nigel McMillan, B. R.G. Williams, A. G. Hovanessian, P. J. Southern

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17 Scopus citations

Abstract

We have analyzed the effect of transfection into murine NIH/3T3 cells of the human dsRNA-activated kinase PKR on the expression of the β-galactosidase reporter gene, placed under control of the HIV1 or the HTLV-I LTR. β-Galactosidase expression is stimulated when the reporter plasmids are cotransfected with wild-type PKR but inhibited when cotransfected with a catalytically inactive mutant PKR. In the case of HIV1, β-galactosidase expression was not stimulated when cotransfection was carried out with PKR harboring mutations in the dsRNA binding domains, indicating that stimulation depends on the classical mode of PKR activation through dsRNA binding. In contrast, the dsRNA binding mutants of PKR could still partially stimulate β-galactosidase expression from the HTLV-I LTR, suggesting that PKR activation in this case may involve different/additional mechanisms. These results show that, in addition to the known down-regulation of protein synthesis through eIF2 phosphorylation, PKR can also positively stimulate gene expressionin vivo, most probably through phosphorylation of a substrate distinct from eIF2.

Original languageEnglish (US)
Article number70080
Pages (from-to)653-659
Number of pages7
JournalVirology
Volume214
Issue number2
DOIs
StatePublished - Dec 20 1995

Bibliographical note

Funding Information:
We thank Michael Emerman and Jakulin Kimpton, for the pJK2 and the pCMV-tat vectors, and Michael Nerenberg for the pHTLV-oligophX. E.F.M. and P.J.S. were supported in part by grants from the National Institutes of Health. B.R.G.W. and A.G.H. were supported by a grant from the International Human Frontier Science Program. A.G.H. was also supported by grants from the Agence Nationale Recherche Scienti-fique.

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