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 W Litchfield, Ola Larsson, Ivan Topisirovic

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42 Citations (Scopus)

Abstract

Ternary complex (TC) and eIF4F complex assembly are the two major rate-limiting steps in translation initiation regulated by eIF2alpha 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 eIF2alpha phosphorylation. During acute nutrient or growth factor stimulation, mTORC1 induces eIF2beta phosphorylation and recruitment of NCK1 to eIF2, decreases eIF2alpha phosphorylation and bolsters TC recycling. Accordingly, eIF2beta 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 eIF2beta 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
Article number11127
Number of pages15
JournalNature Communications
Volume7
DOIs
Publication statusPublished - 4 Apr 2016

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