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J. Biol. Chem., Vol. 276, Issue 13, 9936-9944, March 30, 2001
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From the The interferon-inducible double-stranded RNA
(dsRNA)-activated protein kinase PKR is regulated by dsRNAs that
interact with the two dsRNA-binding motifs (dsRBMs) in its N terminus.
The dsRBM is a conserved protein motif found in many proteins from most organisms. In this study, we investigated the biochemical functions and
cytological activities of the two PKR dsRBMs (dsRBM1 and dsRBM2) and
the cooperation between them. We found that dsRBM1 has a higher affinity for binding to dsRNA than dsRBM2. In addition, dsRBM1 has
RNA-annealing activity that is not displayed by dsRBM2. Both dsRBMs
have an intrinsic ability to dimerize (dsRBM2) or multimerize (dsRBM1).
Binding to dsRNA inhibits oligomerization of dsRBM1 but not dsRBM2 and
strongly inhibits the dimerization of the intact PKR N terminus (p20)
containing both dsRBMs. dsRBM1, like p20, activates reporter gene
expression in transfection assays, and it plays a determinative role in
localizing PKR to the nucleolus and cytoplasm of the cell. Thus, dsRBM2
has weak or no activity in dsRNA binding, stimulation of gene
expression, and PKR localization, but it strongly enhances these
functions of dsRBM1 when contained in p20. However, dsRBM2 does not
enhance the annealing activity of dsRBM1. This study shows that the
dsRBMs of PKR possess distinct properties and that some, but not all,
of the functions of the enzyme depend on cooperation between the two motifs.
Functional Characterization of and Cooperation between the
Double-stranded RNA-binding Motifs of the Protein Kinase PKR*
§¶ and§
Department of Biochemistry and Molecular
Biology and § Graduate School of Biomedical Sciences,
New Jersey Medical School, University of Medicine and Dentistry of New
Jersey, Newark, New Jersey 07103
*
This study was supported in part by Grant AI34552
from the National Institutes of Health.The costs of publication of this article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed. Tel.:
973-972-4411; Fax: 973-972-5594; E-mail: mathews@umdnj.edu.
Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.
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