Dihydropyrimidinase-Related Protein 2 Is a New Partner in the Binding between 4E-BP2 and eIF4E Related to Neuronal Death after Cerebral Ischemia
Transient cerebral ischemia induces neuronal degeneration, followed in time by secondary delayed neuronal death that is strongly correlated with a permanent inhibition of protein synthesis in vulnerable brain regions, while protein translational rates are recovered in resistant areas. In the transla...
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| Format: | Article |
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MDPI AG
2023-05-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/9/8246 |
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| author | Emma Martínez-Alonso Alejandro Escobar-Peso Natalia Guerra-Pérez Marcel Roca Jaime Masjuan Alberto Alcázar |
| author_facet | Emma Martínez-Alonso Alejandro Escobar-Peso Natalia Guerra-Pérez Marcel Roca Jaime Masjuan Alberto Alcázar |
| author_sort | Emma Martínez-Alonso |
| collection | DOAJ |
| description | Transient cerebral ischemia induces neuronal degeneration, followed in time by secondary delayed neuronal death that is strongly correlated with a permanent inhibition of protein synthesis in vulnerable brain regions, while protein translational rates are recovered in resistant areas. In the translation-regulation initiation step, the eukaryotic initiation factor (eIF) 4E is a key player regulated by its association with eIF4E-binding proteins (4E-BPs), mostly 4E-BP2 in brain tissue. In a previous work, we identified dihydropyrimidinase-related protein 2 (DRP2) as a 4E-BP2-interacting protein. Here, using a proteomic approach in a model of transient cerebral ischemia, a detailed study of DRP2 was performed in order to address the challenge of translation restoration in vulnerable regions. In this report, several DRP2 isoforms that have a specific interaction with both 4E-BP2 and eIF4E were identified, showing significant and opposite differences in this association, and being differentially detected in resistant and vulnerable regions in response to ischemia reperfusion. Our results provide the first evidence of DRP2 isoforms as potential regulators of the 4E-BP2–eIF4E association that would have consequences in the delayed neuronal death under ischemic-reperfusion stress. The new knowledge reported here identifies DRP2 as a new target to promote neuronal survival after cerebral ischemia. |
| first_indexed | 2024-03-11T04:16:34Z |
| format | Article |
| id | doaj.art-cfdbe2efe5eb4d8d842c5a3189d4a8e8 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T04:16:34Z |
| publishDate | 2023-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-cfdbe2efe5eb4d8d842c5a3189d4a8e82023-11-17T23:06:56ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-05-01249824610.3390/ijms24098246Dihydropyrimidinase-Related Protein 2 Is a New Partner in the Binding between 4E-BP2 and eIF4E Related to Neuronal Death after Cerebral IschemiaEmma Martínez-Alonso0Alejandro Escobar-Peso1Natalia Guerra-Pérez2Marcel Roca3Jaime Masjuan4Alberto Alcázar5Department of Research, Hospital Universitario Ramón y Cajal, IRYCIS, 28034 Madrid, SpainDepartment of Research, Hospital Universitario Ramón y Cajal, IRYCIS, 28034 Madrid, SpainDepartment of Genetics, Physiology and Microbiology, Faculty of Biological Sciences, Universidad Complutense de Madrid, 28040 Madrid, SpainDepartment of Research, Hospital Universitario Ramón y Cajal, IRYCIS, 28034 Madrid, SpainDepartment of Neurology, Hospital Universitario Ramón y Cajal, IRYCIS, 28034 Madrid, SpainDepartment of Research, Hospital Universitario Ramón y Cajal, IRYCIS, 28034 Madrid, SpainTransient cerebral ischemia induces neuronal degeneration, followed in time by secondary delayed neuronal death that is strongly correlated with a permanent inhibition of protein synthesis in vulnerable brain regions, while protein translational rates are recovered in resistant areas. In the translation-regulation initiation step, the eukaryotic initiation factor (eIF) 4E is a key player regulated by its association with eIF4E-binding proteins (4E-BPs), mostly 4E-BP2 in brain tissue. In a previous work, we identified dihydropyrimidinase-related protein 2 (DRP2) as a 4E-BP2-interacting protein. Here, using a proteomic approach in a model of transient cerebral ischemia, a detailed study of DRP2 was performed in order to address the challenge of translation restoration in vulnerable regions. In this report, several DRP2 isoforms that have a specific interaction with both 4E-BP2 and eIF4E were identified, showing significant and opposite differences in this association, and being differentially detected in resistant and vulnerable regions in response to ischemia reperfusion. Our results provide the first evidence of DRP2 isoforms as potential regulators of the 4E-BP2–eIF4E association that would have consequences in the delayed neuronal death under ischemic-reperfusion stress. The new knowledge reported here identifies DRP2 as a new target to promote neuronal survival after cerebral ischemia.https://www.mdpi.com/1422-0067/24/9/8246cerebral ischemiaeIF4E-binding proteineIF4Ecollapsing-response mediator protein 2dihydropyrimidinase-related protein 2protein phosphorylation |
| spellingShingle | Emma Martínez-Alonso Alejandro Escobar-Peso Natalia Guerra-Pérez Marcel Roca Jaime Masjuan Alberto Alcázar Dihydropyrimidinase-Related Protein 2 Is a New Partner in the Binding between 4E-BP2 and eIF4E Related to Neuronal Death after Cerebral Ischemia International Journal of Molecular Sciences cerebral ischemia eIF4E-binding protein eIF4E collapsing-response mediator protein 2 dihydropyrimidinase-related protein 2 protein phosphorylation |
| title | Dihydropyrimidinase-Related Protein 2 Is a New Partner in the Binding between 4E-BP2 and eIF4E Related to Neuronal Death after Cerebral Ischemia |
| title_full | Dihydropyrimidinase-Related Protein 2 Is a New Partner in the Binding between 4E-BP2 and eIF4E Related to Neuronal Death after Cerebral Ischemia |
| title_fullStr | Dihydropyrimidinase-Related Protein 2 Is a New Partner in the Binding between 4E-BP2 and eIF4E Related to Neuronal Death after Cerebral Ischemia |
| title_full_unstemmed | Dihydropyrimidinase-Related Protein 2 Is a New Partner in the Binding between 4E-BP2 and eIF4E Related to Neuronal Death after Cerebral Ischemia |
| title_short | Dihydropyrimidinase-Related Protein 2 Is a New Partner in the Binding between 4E-BP2 and eIF4E Related to Neuronal Death after Cerebral Ischemia |
| title_sort | dihydropyrimidinase related protein 2 is a new partner in the binding between 4e bp2 and eif4e related to neuronal death after cerebral ischemia |
| topic | cerebral ischemia eIF4E-binding protein eIF4E collapsing-response mediator protein 2 dihydropyrimidinase-related protein 2 protein phosphorylation |
| url | https://www.mdpi.com/1422-0067/24/9/8246 |
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