Human gene profiling in response to the active protein kinase, interferon-induced serine/threonine protein kinase (PKR), in infected cells. Involvement of the transcription factor ATF-3 IN PKR-induced apoptosis

The Journal of Biological Chemistry
S GuerraMariano Esteban

Abstract

The interferon-induced serine/threonine protein kinase (PKR) has an essential role in cell survival and cell death after viral infection and under stress conditions, but the host genes involved in these processes are not well defined. We used human cDNA microarrays to identify, in infected cells, genes differentially expressed after PKR expression and analyzed the requirement of catalytic activity of the enzyme. To express PKR, we used vaccinia virus (VV) recombinants producing wild type PKR (VV-PKR) and the catalytically inactive mutant K296R (VV-PKR-K296R). Most regulated genes were classified according to biological function, including apoptosis, stress, defense, and immune response. Transcriptional changes detected by microarray analysis were confirmed for selected genes by quantitative real time reverse transcription PCR. A total of 111 genes were regulated specifically by PKR catalytic activity. Of these, 97 were up-regulated, and 14 were down-regulated. The ATF-3 transcription factor, involved in stress-induced beta-cell apoptosis, was up-regulated. Activation of endogenous PKR with a VV mutant lacking the viral protein E3L (VVDeltaE3L), a PKR inhibitor, triggered an increase in ATF-3 expression that was not observed in ...Continue Reading

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Citations

Dec 21, 2010·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Agnieszka Pindel, Anthony Sadler
Jun 11, 2010·Journal of Virology·Susana GuerraMariano Esteban
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Jul 8, 2008·PLoS Pathogens·Susana GuerraMariano Esteban
May 30, 2008·Kidney International·Hua ZhouRobert A Star
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Nov 30, 2004·Journal of Molecular Biology·Peter A LemaireJames L Cole
Jul 21, 2017·Expert Reviews in Molecular Medicine·M B Garcia-OrtegaM A Garcia
Feb 27, 2018·Cancer Science·Takao WatanabeYoichi Hiasa
Nov 17, 2019·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jean-Pierre LevraudPierre Boudinot

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