eIF3d specialized translation requires a RACK1-driven eIF3d binding to 43S PIC in proliferating SH-SY5Y neuroblastoma cells

Translation initiation of most mammalian mRNAs is mediated by a 5′ cap structure that binds eukaryotic initiation factor 4E (eIF4E). Notably, most mRNAs are still capped when eIF4E is inhibited, suggesting alternative mechanisms likely mediate cap-dependent mRNA translation without functional eIF4F....

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Veröffentlicht in:Cellular signalling 2025-01, Vol.125, p.111494, Article 111494
Hauptverfasser: Silvestri, Federica, Montuoro, Raffaele, Catalani, Elisabetta, Tilesi, Francesca, Willems, Daniela, Romano, Nicla, Ricciardi, Sara, Cervia, Davide, Ceci, Marcello
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container_start_page 111494
container_title Cellular signalling
container_volume 125
creator Silvestri, Federica
Montuoro, Raffaele
Catalani, Elisabetta
Tilesi, Francesca
Willems, Daniela
Romano, Nicla
Ricciardi, Sara
Cervia, Davide
Ceci, Marcello
description Translation initiation of most mammalian mRNAs is mediated by a 5′ cap structure that binds eukaryotic initiation factor 4E (eIF4E). Notably, most mRNAs are still capped when eIF4E is inhibited, suggesting alternative mechanisms likely mediate cap-dependent mRNA translation without functional eIF4F. Here we found that, when eIF4E is inhibited, the ribosomal scaffold RACK1 recruits eIF3d on the 43S pre-initiation complex. Moreover, we found that it is just PKCBII in its active form that promotes the binding of RACK1 to eIF3d. These studies disclose a previously unknown role of ribosomal RACK1 for eIF3d specialized translation. •eIF3d requires RACK1 for the binding to translational machinery and its activity.•The binding of eIF3d with ribosomal RACK1 is required for the cyclin D2 expression.•The PKCβII modulates the eIF3d-RACK1 binding.•The eIF3d-RACK1 complex is active in mTORC1 blocking conditions.•The eIF3d-RACK1 complex controls the HSP-70 mRNA translation.
doi_str_mv 10.1016/j.cellsig.2024.111494
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subjects Cell Line, Tumor
Cell Proliferation
eIF3d
eIF4E
Eukaryotic Initiation Factor-3 - metabolism
Eukaryotic Initiation Factor-4E - metabolism
HSP-70
Humans
mTORC1
Neoplasm Proteins - metabolism
Neuroblastoma - metabolism
Neuroblastoma - pathology
Protein Binding
Protein Biosynthesis
RACK1
Receptors for Activated C Kinase - metabolism
Ribosomes - metabolism
Translational control
title eIF3d specialized translation requires a RACK1-driven eIF3d binding to 43S PIC in proliferating SH-SY5Y neuroblastoma cells
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