Journal article

+ 3 other files

Global phosphoproteomics pinpoints uncharted Gcn2-mediated mechanisms of translational control


Show more…
  • 2021
Published in:
  • Mol Cell. - 2021, vol. 81, no. 6, p. 1879-1889
English The conserved Gcn2 protein kinase mediates cellular adaptations to amino acid limitation through translational control of gene expression that is exclusively executed by phosphorylation of the α-subunit of the eukaryotic translation initiation factor 2 (eIF2α). Using quantitative phosphoproteomics, however, we discovered that Gcn2 targets auxiliary effectors to modulate translation. Accordingly, Gcn2 also phosphorylates the β-subunit of the trimeric eIF2 G protein complex to promote its association with eIF5, which prevents spontaneous nucleotide exchange on eIF2 and thereby restricts the recycling of the initiator methionyl-tRNA-bound eIF2-GDP ternary complex in amino-acid-starved cells. This mechanism contributes to the inhibition of translation initiation in parallel to the sequestration of the nucleotide exchange factor eIF2B by phosphorylated eIF2α. Gcn2 further phosphorylates Gcn20 to antagonize, in an inhibitory feedback loop, the formation of the Gcn2-stimulatory Gcn1-Gcn20 complex. Thus, Gcn2 plays a substantially more intricate role in controlling translation initiation than hitherto appreciated.
Faculté des sciences et de médecine
Département de Biologie
  • English
Biological sciences
License undefined
Open access status
Persistent URL
Other files


Document views: 25 File downloads:
  • molecular-cell-d-20-01963_r5copy_1.pdf: 70
  • Global_phosphoproteomics_Supplemental_information.pdf: 30
  • mmc2.xlsx: 8
  • Table S2.xlsx: 35