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

doi:10.1038/ncomms11127

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 (Lead / Corresponding author), Ivan Topisirovic (Lead / Corresponding author)

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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.

Original language	English
Article number	11127
Number of pages	15
Journal	Nature Communications
Volume	7
DOIs	https://doi.org/10.1038/ncomms11127
Publication status	Published - 4 Apr 2016

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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, A. E., Asano, K., Litchfield, D., Larsson, O., & Topisirovic, I. (2016). mTORC1 and CK2 coordinate ternary and eIF4F complex assembly. Nature Communications, 7, Article 11127. https://doi.org/10.1038/ncomms11127

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title = "mTORC1 and CK2 coordinate ternary and eIF4F complex assembly",

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.",

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

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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

TY - JOUR

T1 - mTORC1 and CK2 coordinate ternary and eIF4F complex assembly

AU - Gandin, Valentina

AU - Masvidal, Laia

AU - Cargnello, Marie

AU - Gyenis, Laszlo

AU - McLaughlan, Shannon

AU - Cai, Yutian

AU - Tenkerian, Clara

AU - Morita, Masahiro

AU - Balanathan, Preetika

AU - Jean-Jean, Olivier

AU - Stambolic, Vuk

AU - Trost, Matthias

AU - Furic, Luc

AU - Larose, Louise

AU - Koromilas, Antonis E

AU - Asano, Katsura

AU - Litchfield, David

AU - Larsson, Ola

AU - Topisirovic, Ivan

PY - 2016/4/4

Y1 - 2016/4/4

N2 - 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.

AB - 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.

U2 - 10.1038/ncomms11127

DO - 10.1038/ncomms11127

M3 - Article

C2 - 27040916

SN - 2041-1723

VL - 7

JO - Nature Communications

JF - Nature Communications

M1 - 11127

ER -

mTORC1 and CK2 coordinate ternary and eIF4F complex assembly

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