Ribosomal RACK1:Protein Kinase C βII Modulates Intramolecular Interactions between Unstructured Regions of Eukaryotic Initiation Factor 4G (eIF4G) That Control eIF4E and eIF3 Binding

Molecular and Cellular Biology
Mikhail DobrikovMatthias Gromeier

Abstract

The receptor for activated C kinase (RACK1), a conserved constituent of eukaryotic ribosomes, mediates phosphorylation of eukaryotic initiation factor 4G1(S1093) [eIF4G1(S1093)] and eIF3a(S1364) by protein kinase C βII (PKCβII) (M. I. Dobrikov, E. Y. Dobrikova, and M. Gromeier, Mol Cell Biol 38:e00304-18, 2018, https://doi.org/10.1128/MCB.00304-18). RACK1:PKCβII activation drives a phorbol ester-induced surge of global protein synthesis and template-specific translation induction of PKC-Raf-extracellular signal-regulated kinase 1/2 (ERK1/2)-responsive genes. For unraveling mechanisms of RACK1:PKCβII-mediated translation stimulation, we used sequentially truncated eIF4G1 in coimmunoprecipitation analyses to delineate a set of autoinhibitory elements in the N-terminal unstructured region (surrounding the eIF4E-binding motif) and the interdomain linker (within the eIF3-binding site) of eIF4G1. Computer-based predictions of secondary structure, mutational analyses, and fluorescent titration with the β-sheet dye thioflavin T suggest that eIF4G1(S1093) modulates a 4-stranded β-sheet composed of antiparallel β-hairpins formed by the autoinhibitory elements in eIF4G1's unstructured regions. The intact β-sheet "locks" the eIF4G configur...Continue Reading

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Citations

Sep 12, 2018·Molecular and Cellular Biology·Simone GalloStefano Biffo
Aug 17, 2019·Learning & Memory·Ilona R Kats, Eric Klann
Jul 30, 2020·British Journal of Pharmacology·Erica BuosoMarco Racchi
Dec 2, 2018·Frontiers in Genetics·Piera CalamitaStefano Biffo
Jun 17, 2020·Science Advances·Jonathan P KastanMatthias Gromeier
Jul 14, 2020·Wiley Interdisciplinary Reviews. RNA·Clare M MillerGabriele Fuchs
May 12, 2021·Cellular Signalling·Lilas AlboushiSeyed Mehdi Jafarnejad
Apr 21, 2020·Virology·Ethan LaFontaineGabriele Fuchs

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