| Content Provider |
World Health Organization (WHO)-Global Index Medicus |
| Author |
Esteban, Mariano Campagna, Michela Marcos-villar, Laura Lang, Valerie Gutiérrez, Sylvia Rivas, Carmen Rodríguez, Manuel S. Baz-martínez, Maite Vidal, Anxo De La Cruz-herrera, Carlos F. García, Maria A. |
| Description |
Author Affiliation: de la Cruz-Herrera CF ( From the Departamento de Biología Molecular y Celular, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas (CSIC), Darwin 3, Madrid 28049.); Campagna M ( From the Departamento de Biología Molecular y Celular, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas (CSIC), Darwin 3, Madrid 28049.); García MA ( the Unidad de Investigación, Hospital Universitario Virgen de las Nieves, 18014 Granada.); Marcos-Villar L ( From the Departamento de Biología Molecular y Celular, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas (CSIC), Darwin 3, Madrid 28049.); Lang V ( the Ubiquitylation and Cancer Molecular Biology Laboratory, Inbiomed, San Sebastian-Donostia, 20009 Gipuzkoa, Spain.); Baz-Martínez M ( the Centro de Investigación en Medicina Molecular (CIMUS), Universidade de Santiago de Compostela, Instituto de Investigaciones Sanitarias (IDIS), Santiago de Compostela E15782.); Gutiérrez S ( the Confocal Service of Centro Nacional de Biotecnología-CSIC, Darwin 3, Madrid 28049, and.); Vidal A ( the Departamento de Fisioloxía and Centro de Investigación en Medicina Molecular (CIMUS), Universidade de Santiago de Compostela, Instituto de Investigaciones Sanitarias (IDIS), Santiago de Compostela E15782, Spain.); Rodríguez MS ( the Ubiquitylation and Cancer Molecular Biology Laboratory, Inbiomed, San Sebastian-Donostia, 20009 Gipuzkoa, Spain.); Esteban M ( From the Departamento de Biología Molecular y Celular, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas (CSIC), Darwin 3, Madrid 28049.); Rivas C ( From the Departamento de Biología Molecular y Celular, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas (CSIC), Darwin 3, Madrid 28049, the Centro de Investigación en Medicina Molecular (CIMUS), Universidade de Santiago de Compostela, Instituto de Investigaciones San) |
| Abstract |
The dsRNA-dependent kinase PKR is an interferon-inducible protein with ability to phosphorylate the subunit of the eukaryotic initiation factor (eIF)-2 complex, resulting in a shut-off of general translation, induction of apoptosis, and inhibition of virus replication. Here we analyzed the modification of PKR by the small ubiquitin-like modifiers SUMO1 and SUMO2 and evaluated the consequences of PKR SUMOylation. Our results indicate that PKR is modified by both SUMO1 and SUMO2, in vitro and in vivo. We identified lysine residues Lys-60, Lys-150, and Lys-440 as SUMOylation sites in PKR. We show that SUMO is required for efficient PKR-dsRNA binding, PKR dimerization, and eIF2 phosphorylation. Furthermore, we demonstrate that SUMO potentiates the inhibition of protein synthesis induced by PKR in response to dsRNA, whereas a PKR SUMOylation mutant is impaired in its ability to inhibit protein synthesis and shows reduced capability to control vesicular stomatitis virus replication and to induce apoptosis in response to vesicular stomatitis virus infection. In summary, our data demonstrate the important role of SUMO in processes mediated by the activation of PKR. |
| ISSN |
00219258 |
| e-ISSN |
1083351X |
| Journal |
Journal of Biological Chemistry |
| Issue Number |
38 |
| Volume Number |
289 |
| Language |
English |
| Publisher |
American Society for Biochemistry and Molecular Biology (United States) |
| Publisher Date |
2014-09-19 |
| Publisher Place |
United States |
| Access Restriction |
Open |
| Subject Keyword |
SUMO-1 Protein Metabolism Sumoylation EIF-2 Kinase 3T3 Cells Animals Enzyme Activation Host-Pathogen Interactions Immunity, Innate Mice Peptide Mapping Protein Binding Protein Multimerization RNA, Double-Stranded Chemistry RNA, Viral Sequence Analysis, Protein Vesiculovirus Physiology Virus Replication Research Support, Non-U.S. Gov't Biochemistry Molecular Biology |
| Content Type |
Text |
| Resource Type |
Article |
| Subject |
Cell Biology Biochemistry Molecular Biology |
