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Phosphorylation of Eukaryotic Initiation Factor 4G1 (eIF4G1) at Ser1147 Is Specific for eIF4G1 Bound to eIF4E in Delayed Neuronal Death after Ischemia

dc.contributor.authorMartínez Alonso, Emma
dc.contributor.authorGuerra Pérez, Natalia
dc.contributor.authorEscobar Peso, Alejandro
dc.contributor.authorPeracho, Lorena
dc.contributor.authorVera Lechuga, Rocío
dc.contributor.authorCruz Culebras, Antonio
dc.contributor.authorMasjuan, Jaime
dc.contributor.authorAlcázar González, Alberto
dc.date.accessioned2023-06-22T10:51:20Z
dc.date.available2023-06-22T10:51:20Z
dc.date.issued2022-02-06
dc.description.abstractIschemic strokes are caused by a reduction in cerebral blood flow and both the ischemic period and subsequent reperfusion induce brain injury, with different tissue damage depending on the severity of the ischemic insult, its duration, and the particular areas of the brain affected. In those areas vulnerable to cerebral ischemia, the inhibition of protein translation is an essential process of the cellular response leading to delayed neuronal death. In particular, translation initiation is ratelimiting for protein synthesis and the eukaryotic initiation factor (eIF) 4F complex is indispensable for cap-dependent protein translation. In the eIF4F complex, eIF4G is a scaffolding protein that provides docking sites for the assembly of eIF4A and eIF4E, binding to the cap structure of the mRNA and stabilizing all proteins of the complex. The eIF4F complex constituents, eIF4A, eIF4E, and eIF4G, participate in translation regulation by their phosphorylation at specific sites under cellular stress conditions, modulating the activity of the cap-binding complex and protein translation. This work investigates the phosphorylation of eIF4G1 involved in the eIF4E/eIF4G1 association complex, and their regulation in ischemia-reperfusion (IR) as a stress-inducing condition. IR was induced in an animal model of transient cerebral ischemia and the results were studied in the resistant cortical region and in the vulnerable hippocampal CA1 region. The presented data demonstrate the phosphorylation of eIF4G1 at Ser1147, Ser1185, and Ser1231 in both brain regions and in control and ischemic conditions, being the phosphorylation of eIF4G1 at Ser1147 the only one found in the eIF4E/eIF4G association complex from the cap-containing matrix (m7GTP-Sepharose). In addition, our work reveals the specific modulation of the phosphorylation of eIF4G1 at Ser1147 in the vulnerable region, with increased levels and colocalization with eIF4E in response to IR. These findings contribute to elucidate the molecular mechanism of protein translation regulation that underlies in the balance of cell survival/death during pathophysiological stress, such as cerebral ischemia.
dc.description.departmentDepto. de Genética, Fisiología y Microbiología
dc.description.facultyFac. de Ciencias Biológicas
dc.description.refereedTRUE
dc.description.sponsorshipInstituto de Salud Carlos III (ISCIII)/FEDER
dc.description.statuspub
dc.eprint.idhttps://eprints.ucm.es/id/eprint/73508
dc.identifier.doi10.3390/ijms23031830
dc.identifier.issn1661-6596, ESSN: 1422-0067
dc.identifier.officialurlhttps://doi.org/10.3390/ijms23031830
dc.identifier.relatedurlhttps://www.mdpi.com/1422-0067/23/3/1830
dc.identifier.urihttps://hdl.handle.net/20.500.14352/71788
dc.issue.number3
dc.journal.titleInternational Journal of Molecular Sciences
dc.language.isoeng
dc.page.final17
dc.page.initial1
dc.publisherMDPI
dc.relation.projectID(PI18/00255 and RETICS RD16/0019/0006 and RD21/0006/0019)
dc.rightsAtribución 3.0 España
dc.rights.accessRightsopen access
dc.rights.urihttps://creativecommons.org/licenses/by/3.0/es/
dc.subject.cdu577.112
dc.subject.cdu616.831-005.4
dc.subject.cdu612.8
dc.subject.keywordCerebral ischemia
dc.subject.keywordeIF4E
dc.subject.keywordeIF4G1
dc.subject.keywordProtein synthesis regulation
dc.subject.keywordProtein phosphorylation
dc.subject.keywordNeuronal death
dc.subject.keywordVulnerable regions
dc.subject.keywordConfocal microscopy
dc.subject.ucmBioquímica (Biología)
dc.subject.ucmNeurociencias (Biológicas)
dc.subject.unesco2302 Bioquímica
dc.subject.unesco2490 Neurociencias
dc.titlePhosphorylation of Eukaryotic Initiation Factor 4G1 (eIF4G1) at Ser1147 Is Specific for eIF4G1 Bound to eIF4E in Delayed Neuronal Death after Ischemia
dc.typejournal article
dc.volume.number23
dspace.entity.typePublication
relation.isAuthorOfPublication25551a6d-4113-4833-aa8e-85c3eee7da2d
relation.isAuthorOfPublication.latestForDiscovery25551a6d-4113-4833-aa8e-85c3eee7da2d

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