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PMID: 17158706 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Review

Impact of protein kinase PKR in cell biology: from antiviral to antiproliferative action.

Microbiology and molecular biology reviews : MMBR ·Vol. 70 ·No. 4 ·2006-12-00 ·Pages 1032-60

García MA, Gil J, Ventoso I, Guerra S, Domingo E, Rivas C, Esteban M

Abstract

The double-stranded RNA-dependent protein kinase PKR is a critical mediator of the antiproliferative and antiviral effects exerted by interferons. Not only is PKR an effector molecule on the cellular response to double-stranded RNA, but it also integrates signals in response to Toll-like receptor activation, growth factors, and diverse cellular stresses. In this review, we provide a detailed picture on how signaling downstream of PKR unfolds and what are the ultimate consequences for the cell fate. PKR activation affects both transcription and translation. PKR phosphorylation of the alpha subunit of eukaryotic initiation factor 2 results in a blockade on translation initiation. However, PKR cannot avoid the translation of some cellular and viral mRNAs bearing special features in their 5' untranslated regions. In addition, PKR affects diverse transcriptional factors such as interferon regulatory factor 1, STATs, p53, activating transcription factor 3, and NF-kappaB. In particular, how PKR triggers a cascade of events involving IKK phosphorylation of IkappaB and NF-kappaB nuclear translocation has been intensively studied. At the cellular and organism levels PKR exerts antiproliferative effects, and it is a key antiviral agent. A point of convergence in both effects is that PKR activation results in apoptosis induction. The extent and strength of the antiviral action of PKR are clearly understood by the findings that unrelated viral proteins of animal viruses have evolved to inhibit PKR action by using diverse strategies. The case for the pathological consequences of the antiproliferative action of PKR is less understood, but therapeutic strategies aimed at targeting PKR are beginning to offer promising results.

MeSH Terms
Animals Antiviral Agents/pharmacology Cell Biology Cells/drug effects Humans Interferons/pharmacology Signal Transduction/drug effects eIF-2 Kinase/physiology
Chemicals
Antiviral Agents Interferons eIF-2 Kinase
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
García M A
Department of Molecular and Cellular Biology, Centro Nacional de Biotecnología, Ciudad Universitaria Cantoblanco, 28049 Madrid, Spain.
Gil J
Ventoso I
Guerra S
Domingo E
Rivas C
Esteban M
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Article Info
Journal
Microbiology and molecular biology reviews : MMBR
Abbr.
Microbiol Mol Biol Rev
ISSN
1092-2172
DOI
10.1128/MMBR.00027-06
Published
2006-12-00
Pages
1032-60
Language
English
Region
United States
NLM ID
9706653
PMCID
PMC1698511
Subset
IM
Grants
Medical Research Council · MC_U120085810 · United Kingdom
External Links
PubMed source DOI: 10.1128/MMBR.00027-06 PMC Full Text View journal details
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