Nucleic Acids Research Advance Access originally published online on December 20, 2007
Nucleic Acids Research 2008 36(3):998-1008; doi:10.1093/nar/gkm1129
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Nucleic Acids Research, 2008, Vol. 36, No. 3 998-1008
© 2007 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Molecular Biology |
Interaction of human tRNA-dihydrouridine synthase-2 with interferon-induced protein kinase PKR
1Department of Biological Sciences and 2Department of Cell, Developmental Biology and Anatomy, University of South Carolina Columbia, SC 29208, USA
*To whom correspondence should be addressed. Tel: +1 803 777 1853; Fax: +1 803 777 4002; Email: patelr{at}biol.sc.edu
Received November 7, 2007. Revised December 4, 2007. Accepted December 4, 2007.
PKR is an interferon (IFN)-induced protein kinase, which is involved in regulation of antiviral innate immunity, stress signaling, cell proliferation and programmed cell death. Although a low amount of PKR is expressed ubiquitously in all cell types in the absence of IFNs, PKR expression is induced at transcriptional level by IFN. PKR's enzymatic activity is activated by its binding to one of its activators. Double-stranded (ds) RNA, protein activator PACT and heparin are the three known activators of PKR. Activation of PKR in cells leads to a general block in protein synthesis due to phosphorylation of eIF2
on serine 51 by PKR. PKR activation is regulated very tightly in mammalian cells and a prolonged activation of PKR leads to apoptosis. Thus, positive and negative regulation of PKR activation is important for cell viability and function. The studies presented here describe human dihydrouridine synthase-2 (hDUS2) as a novel regulator of PKR. We originally identified hDUS2 as a protein interacting with PACT in a yeast two-hybrid screen. Further characterization revealed that hDUS2 also interacts with PKR through its dsRNA binding/dimerization domain and inhibits its kinase activity. Our results suggest that hDUS2 may act as a novel inhibitor of PKR in cells.
The authors wish it to be known that, in their opinion, the first two authors should be regarded as joint First Authors