MTORC1 and CK2 Coordinate Ternary and EIF4F Complex Assembly

Overview

Journal Nat Commun

Specialty Biology

Date 2016 Apr 5

PMID 27040916

Citations 52

Authors

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

Affiliations

Soon will be listed here.

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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