dsRNA-Dependent Protein Kinase PKR and its Role in Stress, Signaling and HCV Infection
The double-stranded RNA-dependent protein kinase PKR plays multiple roles in cells, in response to different stress situations. As a member of the interferon (IFN)‑Stimulated Genes, PKR was initially recognized as an actor in the antiviral action of IFN, due to its ability to control translation, th...
| Main Authors: | , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2012-10-01
|
| Series: | Viruses |
| Subjects: | |
| Online Access: | http://www.mdpi.com/1999-4915/4/11/2598 |
| _version_ | 1818943514057113600 |
|---|---|
| author | Eliane F. Meurs Stéphanie Dabo |
| author_facet | Eliane F. Meurs Stéphanie Dabo |
| author_sort | Eliane F. Meurs |
| collection | DOAJ |
| description | The double-stranded RNA-dependent protein kinase PKR plays multiple roles in cells, in response to different stress situations. As a member of the interferon (IFN)‑Stimulated Genes, PKR was initially recognized as an actor in the antiviral action of IFN, due to its ability to control translation, through phosphorylation, of the alpha subunit of eukaryotic initiation factor 2 (eIF2a). As such, PKR participates in the generation of stress granules, or autophagy and a number of viruses have designed strategies to inhibit its action. However, PKR deficient mice resist most viral infections, indicating that PKR may play other roles in the cell other than just acting as an antiviral agent. Indeed, PKR regulates several signaling pathways, either as an adapter protein and/or using its kinase activity. Here we review the role of PKR as an eIF2a kinase, its participation in the regulation of the NF-kB, p38MAPK and insulin pathways, and we focus on its role during infection with the hepatitis C virus (HCV). PKR binds the HCV IRES RNA, cooperates with some functions of the HCV core protein and may represent a target for NS5A or E2. Novel data points out for a role of PKR as a pro-HCV agent, both as an adapter protein and as an eIF2a-kinase, and in cooperation with the di-ubiquitin-like protein ISG15. Developing pharmaceutical inhibitors of PKR may help in resolving some viral infections as well as stress-related damages. |
| first_indexed | 2024-12-20T07:28:32Z |
| format | Article |
| id | doaj.art-2c9ea196380a41df9091fb0faff3b634 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-12-20T07:28:32Z |
| publishDate | 2012-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-2c9ea196380a41df9091fb0faff3b6342022-12-21T19:48:28ZengMDPI AGViruses1999-49152012-10-014112598263510.3390/v4112598dsRNA-Dependent Protein Kinase PKR and its Role in Stress, Signaling and HCV InfectionEliane F. MeursStéphanie DaboThe double-stranded RNA-dependent protein kinase PKR plays multiple roles in cells, in response to different stress situations. As a member of the interferon (IFN)‑Stimulated Genes, PKR was initially recognized as an actor in the antiviral action of IFN, due to its ability to control translation, through phosphorylation, of the alpha subunit of eukaryotic initiation factor 2 (eIF2a). As such, PKR participates in the generation of stress granules, or autophagy and a number of viruses have designed strategies to inhibit its action. However, PKR deficient mice resist most viral infections, indicating that PKR may play other roles in the cell other than just acting as an antiviral agent. Indeed, PKR regulates several signaling pathways, either as an adapter protein and/or using its kinase activity. Here we review the role of PKR as an eIF2a kinase, its participation in the regulation of the NF-kB, p38MAPK and insulin pathways, and we focus on its role during infection with the hepatitis C virus (HCV). PKR binds the HCV IRES RNA, cooperates with some functions of the HCV core protein and may represent a target for NS5A or E2. Novel data points out for a role of PKR as a pro-HCV agent, both as an adapter protein and as an eIF2a-kinase, and in cooperation with the di-ubiquitin-like protein ISG15. Developing pharmaceutical inhibitors of PKR may help in resolving some viral infections as well as stress-related damages.http://www.mdpi.com/1999-4915/4/11/2598PKRdsRNAIFNeIF2aPRRHCVMAVSISG15RIG-I |
| spellingShingle | Eliane F. Meurs Stéphanie Dabo dsRNA-Dependent Protein Kinase PKR and its Role in Stress, Signaling and HCV Infection Viruses PKR dsRNA IFN eIF2a PRR HCV MAVS ISG15 RIG-I |
| title | dsRNA-Dependent Protein Kinase PKR and its Role in Stress, Signaling and HCV Infection |
| title_full | dsRNA-Dependent Protein Kinase PKR and its Role in Stress, Signaling and HCV Infection |
| title_fullStr | dsRNA-Dependent Protein Kinase PKR and its Role in Stress, Signaling and HCV Infection |
| title_full_unstemmed | dsRNA-Dependent Protein Kinase PKR and its Role in Stress, Signaling and HCV Infection |
| title_short | dsRNA-Dependent Protein Kinase PKR and its Role in Stress, Signaling and HCV Infection |
| title_sort | dsrna dependent protein kinase pkr and its role in stress signaling and hcv infection |
| topic | PKR dsRNA IFN eIF2a PRR HCV MAVS ISG15 RIG-I |
| url | http://www.mdpi.com/1999-4915/4/11/2598 |
| work_keys_str_mv | AT elianefmeurs dsrnadependentproteinkinasepkranditsroleinstresssignalingandhcvinfection AT stephaniedabo dsrnadependentproteinkinasepkranditsroleinstresssignalingandhcvinfection |