MTORC1 and CK2 coordinate ternary and eIF4F complex assembly

Valentina Gandin, Laia Masvidal, Marie Cargnello, Laszlo Gyenis, Shannon McLaughlan, Yutian Cai, Clara Tenkerian, Masahiro Morita, Preetika Balanathan, Olivier Jean-Jean, Vuk Stambolic, Matthias Trost, Luc Furic, Louise Larose, Antonis E. Koromilas, Katsura Asano, David Litchfield, Ola Larsson, Ivan Topisirovic

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Ternary complex (TC) and eIF4F complex assembly are the two major rate-limiting steps in translation initiation regulated by eIF2α phosphorylation and the mTOR/4E-BP pathway, respectively. How TC and eIF4F assembly are coordinated, however, remains largely unknown. We show that mTOR suppresses translation of mRNAs activated under short-term stress wherein TC recycling is attenuated by eIF2α phosphorylation. During acute nutrient or growth factor stimulation, mTORC1 induces eIF2β phosphorylation and recruitment of NCK1 to eIF2, decreases eIF2α phosphorylation and bolsters TC recycling. Accordingly, eIF2β mediates the effect of mTORC1 on protein synthesis and proliferation. In addition, we demonstrate a formerly undocumented role for CK2 in regulation of translation initiation, whereby CK2 stimulates phosphorylation of eIF2β and simultaneously bolsters eIF4F complex assembly via the mTORC1/4E-BP pathway. These findings imply a previously unrecognized mode of translation regulation, whereby mTORC1 and CK2 coordinate TC and eIF4F complex assembly to stimulate cell proliferation.

Original languageEnglish (US)
Article number11127
JournalNature Communications
Volume7
DOIs
StatePublished - Apr 4 2016
Externally publishedYes

Fingerprint

phosphorylation
Phosphorylation
assembly
Recycling
recycling
protein synthesis
Cell proliferation
nutrients
Protein Biosynthesis
stimulation
Nutrients
Intercellular Signaling Peptides and Proteins
Cell Proliferation
Food
Messenger RNA
mechanistic target of rapamycin complex 1
Proteins

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Gandin, V., Masvidal, L., Cargnello, M., Gyenis, L., McLaughlan, S., Cai, Y., ... Topisirovic, I. (2016). MTORC1 and CK2 coordinate ternary and eIF4F complex assembly. Nature Communications, 7, [11127]. https://doi.org/10.1038/ncomms11127

MTORC1 and CK2 coordinate ternary and eIF4F complex assembly. / Gandin, Valentina; Masvidal, Laia; Cargnello, Marie; Gyenis, Laszlo; McLaughlan, Shannon; Cai, Yutian; Tenkerian, Clara; Morita, Masahiro; Balanathan, Preetika; Jean-Jean, Olivier; Stambolic, Vuk; Trost, Matthias; Furic, Luc; Larose, Louise; Koromilas, Antonis E.; Asano, Katsura; Litchfield, David; Larsson, Ola; Topisirovic, Ivan.

In: Nature Communications, Vol. 7, 11127, 04.04.2016.

Research output: Contribution to journalArticle

Gandin, V, Masvidal, L, Cargnello, M, Gyenis, L, McLaughlan, S, Cai, Y, Tenkerian, C, Morita, M, Balanathan, P, Jean-Jean, O, Stambolic, V, Trost, M, Furic, L, Larose, L, Koromilas, AE, Asano, K, Litchfield, D, Larsson, O & Topisirovic, I 2016, 'MTORC1 and CK2 coordinate ternary and eIF4F complex assembly', Nature Communications, vol. 7, 11127. https://doi.org/10.1038/ncomms11127
Gandin V, Masvidal L, Cargnello M, Gyenis L, McLaughlan S, Cai Y et al. MTORC1 and CK2 coordinate ternary and eIF4F complex assembly. Nature Communications. 2016 Apr 4;7. 11127. https://doi.org/10.1038/ncomms11127
Gandin, Valentina ; Masvidal, Laia ; Cargnello, Marie ; Gyenis, Laszlo ; McLaughlan, Shannon ; Cai, Yutian ; Tenkerian, Clara ; Morita, Masahiro ; Balanathan, Preetika ; Jean-Jean, Olivier ; Stambolic, Vuk ; Trost, Matthias ; Furic, Luc ; Larose, Louise ; Koromilas, Antonis E. ; Asano, Katsura ; Litchfield, David ; Larsson, Ola ; Topisirovic, Ivan. / MTORC1 and CK2 coordinate ternary and eIF4F complex assembly. In: Nature Communications. 2016 ; Vol. 7.
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abstract = "Ternary complex (TC) and eIF4F complex assembly are the two major rate-limiting steps in translation initiation regulated by eIF2α phosphorylation and the mTOR/4E-BP pathway, respectively. How TC and eIF4F assembly are coordinated, however, remains largely unknown. We show that mTOR suppresses translation of mRNAs activated under short-term stress wherein TC recycling is attenuated by eIF2α phosphorylation. During acute nutrient or growth factor stimulation, mTORC1 induces eIF2β phosphorylation and recruitment of NCK1 to eIF2, decreases eIF2α phosphorylation and bolsters TC recycling. Accordingly, eIF2β mediates the effect of mTORC1 on protein synthesis and proliferation. In addition, we demonstrate a formerly undocumented role for CK2 in regulation of translation initiation, whereby CK2 stimulates phosphorylation of eIF2β and simultaneously bolsters eIF4F complex assembly via the mTORC1/4E-BP pathway. These findings imply a previously unrecognized mode of translation regulation, whereby mTORC1 and CK2 coordinate TC and eIF4F complex assembly to stimulate cell proliferation.",
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AU - Cai, Yutian

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AU - Larose, Louise

AU - Koromilas, Antonis E.

AU - Asano, Katsura

AU - Litchfield, David

AU - Larsson, Ola

AU - Topisirovic, Ivan

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