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 () and Ivan Topisirovic ()
Additional contact information
Valentina Gandin: Lady Davis Institute, SMBD JGH, McGill University
Laia Masvidal: Science for Life Laboratory, Karolinska Institutet
Marie Cargnello: Lady Davis Institute, SMBD JGH, McGill University
Laszlo Gyenis: Schulich School of Medicine & Dentistry, Western University, London
Shannon McLaughlan: Lady Davis Institute, SMBD JGH, McGill University
Yutian Cai: Lady Davis Institute, SMBD JGH, McGill University
Clara Tenkerian: Lady Davis Institute, SMBD JGH, McGill University
Masahiro Morita: McGill University
Preetika Balanathan: Cancer Program, Monash University
Olivier Jean-Jean: UPMC Univ Paris 06, CNRS-UMR8256
Vuk Stambolic: Princess Margaret Cancer Centre, University Health Network, University of Toronto
Matthias Trost: MRC Protein Phosphorylation and Ubiquitylation Unit, University of Dundee
Luc Furic: Cancer Program, Monash University
Louise Larose: Polypeptide Laboratory, McGill University and The Research Institute of McGill University Health Centre
Antonis E. Koromilas: Lady Davis Institute, SMBD JGH, McGill University
Katsura Asano: Molecular Cellular and Developmental Biology Program, Kansas State University
David Litchfield: Schulich School of Medicine & Dentistry, Western University, London
Ola Larsson: Science for Life Laboratory, Karolinska Institutet
Ivan Topisirovic: Lady Davis Institute, SMBD JGH, McGill University

Nature Communications, 2016, vol. 7, issue 1, 1-15

Abstract: 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.

Date: 2016
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DOI: 10.1038/ncomms11127

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