mTORC1 and CK2 coordinate ternary and eIF4F complex assembly
Identifieur interne : 003357 ( Ncbi/Merge ); précédent : 003356; suivant : 003358mTORC1 and CK2 coordinate ternary and eIF4F complex assembly
Auteurs : Valentina Gandin [Canada] ; Laia Masvidal [Suède] ; Marie Cargnello [Canada] ; Laszlo Gyenis [Canada] ; Shannon Mclaughlan [Canada] ; Yutian Cai [Canada] ; Clara Tenkerian [Canada] ; Masahiro Morita [Canada] ; Preetika Balanathan [Australie] ; Olivier Jean-Jean [France] ; Vuk Stambolic [Canada] ; Matthias Trost [Royaume-Uni] ; Luc Furic [Australie] ; Louise Larose [Canada] ; Antonis E. Koromilas [Canada] ; Katsura Asano [États-Unis] ; David Litchfield [Canada] ; Ola Larsson [Suède] ; Ivan Topisirovic [Canada]Source :
- Nature Communications [ 2041-1723 ] ; 2016.
Descripteurs français
- KwdFr :
- Casein Kinase II (génétique), Casein Kinase II (métabolisme), Casein Kinase II (physiologie), Cellules HEK293, Cellules MCF-7, Complexes multiprotéiques (génétique), Complexes multiprotéiques (métabolisme), Complexes multiprotéiques (physiologie), Facteur-2 d'initiation eucaryote (métabolisme), Facteur-2 d'initiation eucaryote (physiologie), Facteur-4F d'initiation eucaryote (métabolisme), Facteurs du complexe ternaire (métabolisme), Humains, Initiation de la traduction, Modèles génétiques, Phosphorylation, Protéines adaptatrices de la transduction du signal (métabolisme), Protéines oncogènes (métabolisme), Régulation de l'expression des gènes, Stress physiologique, Sérine-thréonine kinases TOR (génétique), Sérine-thréonine kinases TOR (métabolisme), Sérine-thréonine kinases TOR (physiologie), Transduction du signal.
- MESH :
- génétique : Casein Kinase II, Complexes multiprotéiques, Sérine-thréonine kinases TOR.
- métabolisme : Casein Kinase II, Complexes multiprotéiques, Facteur-2 d'initiation eucaryote, Facteur-4F d'initiation eucaryote, Facteurs du complexe ternaire, Protéines adaptatrices de la transduction du signal, Protéines oncogènes, Sérine-thréonine kinases TOR.
- physiologie : Casein Kinase II, Complexes multiprotéiques, Facteur-2 d'initiation eucaryote, Sérine-thréonine kinases TOR.
- Cellules HEK293, Cellules MCF-7, Humains, Initiation de la traduction, Modèles génétiques, Phosphorylation, Régulation de l'expression des gènes, Stress physiologique, Transduction du signal.
English descriptors
- KwdEn :
- Adaptor Proteins, Signal Transducing (metabolism), Casein Kinase II (genetics), Casein Kinase II (metabolism), Casein Kinase II (physiology), Eukaryotic Initiation Factor-2 (metabolism), Eukaryotic Initiation Factor-2 (physiology), Eukaryotic Initiation Factor-4F (metabolism), Gene Expression Regulation, HEK293 Cells, Humans, MCF-7 Cells, Models, Genetic, Multiprotein Complexes (genetics), Multiprotein Complexes (metabolism), Multiprotein Complexes (physiology), Oncogene Proteins (metabolism), Peptide Chain Initiation, Translational, Phosphorylation, Signal Transduction, Stress, Physiological, TOR Serine-Threonine Kinases (genetics), TOR Serine-Threonine Kinases (metabolism), TOR Serine-Threonine Kinases (physiology), Ternary Complex Factors (metabolism).
- MESH :
- chemical , genetics : Casein Kinase II, Multiprotein Complexes, TOR Serine-Threonine Kinases.
- chemical , metabolism : Adaptor Proteins, Signal Transducing, Casein Kinase II, Eukaryotic Initiation Factor-2, Eukaryotic Initiation Factor-4F, Multiprotein Complexes, Oncogene Proteins, TOR Serine-Threonine Kinases, Ternary Complex Factors.
- chemical , physiology : Casein Kinase II, Eukaryotic Initiation Factor-2, Multiprotein Complexes, TOR Serine-Threonine Kinases.
- Gene Expression Regulation, HEK293 Cells, Humans, MCF-7 Cells, Models, Genetic, Peptide Chain Initiation, Translational, Phosphorylation, Signal Transduction, Stress, Physiological.
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.
Url:
DOI: 10.1038/ncomms11127
PubMed: 27040916
PubMed Central: 4822005
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PMC:4822005Le document en format XML
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<author><name sortKey="Furic, Luc" sort="Furic, Luc" uniqKey="Furic L" first="Luc" last="Furic">Luc Furic</name>
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<country xml:lang="fr">Australie</country>
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<country xml:lang="fr">Canada</country>
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<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<affiliation wicri:level="1"><nlm:aff id="a4"><institution>Department of Experimental Medicine, McGill University</institution>
, Montreal, Quebec,<country>Canada</country>
H3T 1E2</nlm:aff>
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<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<country xml:lang="fr">Canada</country>
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<author><name sortKey="Larsson, Ola" sort="Larsson, Ola" uniqKey="Larsson O" first="Ola" last="Larsson">Ola Larsson</name>
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<country xml:lang="fr">Suède</country>
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<country xml:lang="fr">Canada</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<affiliation wicri:level="1"><nlm:aff id="a2"><institution>Department of Oncology, McGill University</institution>
, Montreal, Quebec,<country>Canada</country>
H3T 1E2</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="a3"><institution>Department of Biochemistry, McGill University</institution>
, Montreal, Quebec,<country>Canada</country>
H3T 1E2</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="a4"><institution>Department of Experimental Medicine, McGill University</institution>
, Montreal, Quebec,<country>Canada</country>
H3T 1E2</nlm:aff>
<country xml:lang="fr">Canada</country>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">mTORC1 and CK2 coordinate ternary and eIF4F complex assembly</title>
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H3T 1E2</nlm:aff>
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, Montreal, Quebec,<country>Canada</country>
H3T 1E2</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="a3"><institution>Department of Biochemistry, McGill University</institution>
, Montreal, Quebec,<country>Canada</country>
H3T 1E2</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="a4"><institution>Department of Experimental Medicine, McGill University</institution>
, Montreal, Quebec,<country>Canada</country>
H3T 1E2</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Gyenis, Laszlo" sort="Gyenis, Laszlo" uniqKey="Gyenis L" first="Laszlo" last="Gyenis">Laszlo Gyenis</name>
<affiliation wicri:level="1"><nlm:aff id="a6"><institution>Departments of Biochemistry and Oncology, Schulich School of Medicine & Dentistry, Western University, London</institution>
, Ontario,<country>Canada</country>
N6A 4L6</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Mclaughlan, Shannon" sort="Mclaughlan, Shannon" uniqKey="Mclaughlan S" first="Shannon" last="Mclaughlan">Shannon Mclaughlan</name>
<affiliation wicri:level="1"><nlm:aff id="a1"><institution>Lady Davis Institute, SMBD JGH, McGill University</institution>
, Montreal, Quebec,<country>Canada</country>
H3T 1E2</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="a2"><institution>Department of Oncology, McGill University</institution>
, Montreal, Quebec,<country>Canada</country>
H3T 1E2</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="a3"><institution>Department of Biochemistry, McGill University</institution>
, Montreal, Quebec,<country>Canada</country>
H3T 1E2</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="a4"><institution>Department of Experimental Medicine, McGill University</institution>
, Montreal, Quebec,<country>Canada</country>
H3T 1E2</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Cai, Yutian" sort="Cai, Yutian" uniqKey="Cai Y" first="Yutian" last="Cai">Yutian Cai</name>
<affiliation wicri:level="1"><nlm:aff id="a1"><institution>Lady Davis Institute, SMBD JGH, McGill University</institution>
, Montreal, Quebec,<country>Canada</country>
H3T 1E2</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="a3"><institution>Department of Biochemistry, McGill University</institution>
, Montreal, Quebec,<country>Canada</country>
H3T 1E2</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Tenkerian, Clara" sort="Tenkerian, Clara" uniqKey="Tenkerian C" first="Clara" last="Tenkerian">Clara Tenkerian</name>
<affiliation wicri:level="1"><nlm:aff id="a1"><institution>Lady Davis Institute, SMBD JGH, McGill University</institution>
, Montreal, Quebec,<country>Canada</country>
H3T 1E2</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="a6"><institution>Departments of Biochemistry and Oncology, Schulich School of Medicine & Dentistry, Western University, London</institution>
, Ontario,<country>Canada</country>
N6A 4L6</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Morita, Masahiro" sort="Morita, Masahiro" uniqKey="Morita M" first="Masahiro" last="Morita">Masahiro Morita</name>
<affiliation wicri:level="1"><nlm:aff id="a3"><institution>Department of Biochemistry, McGill University</institution>
, Montreal, Quebec,<country>Canada</country>
H3T 1E2</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Balanathan, Preetika" sort="Balanathan, Preetika" uniqKey="Balanathan P" first="Preetika" last="Balanathan">Preetika Balanathan</name>
<affiliation wicri:level="1"><nlm:aff id="a7"><institution>Cancer Program, Biomedicine Discovery Institute and Department of Anatomy and Developmental Biology, Monash University</institution>
, Victoria 3168,<country>Australia</country>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Jean Jean, Olivier" sort="Jean Jean, Olivier" uniqKey="Jean Jean O" first="Olivier" last="Jean-Jean">Olivier Jean-Jean</name>
<affiliation wicri:level="1"><nlm:aff id="a8"><institution>UPMC Univ Paris 06, CNRS-UMR8256</institution>
, Paris 75005,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Stambolic, Vuk" sort="Stambolic, Vuk" uniqKey="Stambolic V" first="Vuk" last="Stambolic">Vuk Stambolic</name>
<affiliation wicri:level="1"><nlm:aff id="a9"><institution>Princess Margaret Cancer Centre, University Health Network, and the Department of Medical Biophysics, University of Toronto</institution>
, Toronto, Ontario,<country>Canada</country>
M5G 1L7</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Trost, Matthias" sort="Trost, Matthias" uniqKey="Trost M" first="Matthias" last="Trost">Matthias Trost</name>
<affiliation wicri:level="1"><nlm:aff id="a10"><institution>MRC Protein Phosphorylation and Ubiquitylation Unit, University of Dundee</institution>
, Scotland DD1 5EH,<country>UK</country>
</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Furic, Luc" sort="Furic, Luc" uniqKey="Furic L" first="Luc" last="Furic">Luc Furic</name>
<affiliation wicri:level="1"><nlm:aff id="a7"><institution>Cancer Program, Biomedicine Discovery Institute and Department of Anatomy and Developmental Biology, Monash University</institution>
, Victoria 3168,<country>Australia</country>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Larose, Louise" sort="Larose, Louise" uniqKey="Larose L" first="Louise" last="Larose">Louise Larose</name>
<affiliation wicri:level="1"><nlm:aff id="a11"><institution>Department of Medicine, Polypeptide Laboratory, McGill University and The Research Institute of McGill University Health Centre</institution>
, Montreal, Quebec,<country>Canada</country>
H3A 2B2</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Koromilas, Antonis E" sort="Koromilas, Antonis E" uniqKey="Koromilas A" first="Antonis E." last="Koromilas">Antonis E. Koromilas</name>
<affiliation wicri:level="1"><nlm:aff id="a1"><institution>Lady Davis Institute, SMBD JGH, McGill University</institution>
, Montreal, Quebec,<country>Canada</country>
H3T 1E2</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="a4"><institution>Department of Experimental Medicine, McGill University</institution>
, Montreal, Quebec,<country>Canada</country>
H3T 1E2</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="a6"><institution>Departments of Biochemistry and Oncology, Schulich School of Medicine & Dentistry, Western University, London</institution>
, Ontario,<country>Canada</country>
N6A 4L6</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Asano, Katsura" sort="Asano, Katsura" uniqKey="Asano K" first="Katsura" last="Asano">Katsura Asano</name>
<affiliation wicri:level="1"><nlm:aff id="a12"><institution>Molecular Cellular and Developmental Biology Program, Division of Biology, Kansas State University</institution>
, Manhattan, Kansas 66506,<country>USA</country>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Litchfield, David" sort="Litchfield, David" uniqKey="Litchfield D" first="David" last="Litchfield">David Litchfield</name>
<affiliation wicri:level="1"><nlm:aff id="a6"><institution>Departments of Biochemistry and Oncology, Schulich School of Medicine & Dentistry, Western University, London</institution>
, Ontario,<country>Canada</country>
N6A 4L6</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Larsson, Ola" sort="Larsson, Ola" uniqKey="Larsson O" first="Ola" last="Larsson">Ola Larsson</name>
<affiliation wicri:level="1"><nlm:aff id="a5"><institution>Department of Oncology-Pathology, Science for Life Laboratory, Karolinska Institutet</institution>
, Stockholm 171 76,<country>Sweden</country>
</nlm:aff>
<country xml:lang="fr">Suède</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Topisirovic, Ivan" sort="Topisirovic, Ivan" uniqKey="Topisirovic I" first="Ivan" last="Topisirovic">Ivan Topisirovic</name>
<affiliation wicri:level="1"><nlm:aff id="a1"><institution>Lady Davis Institute, SMBD JGH, McGill University</institution>
, Montreal, Quebec,<country>Canada</country>
H3T 1E2</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="a2"><institution>Department of Oncology, McGill University</institution>
, Montreal, Quebec,<country>Canada</country>
H3T 1E2</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="a3"><institution>Department of Biochemistry, McGill University</institution>
, Montreal, Quebec,<country>Canada</country>
H3T 1E2</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="a4"><institution>Department of Experimental Medicine, McGill University</institution>
, Montreal, Quebec,<country>Canada</country>
H3T 1E2</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
</analytic>
<series><title level="j">Nature Communications</title>
<idno type="eISSN">2041-1723</idno>
<imprint><date when="2016">2016</date>
</imprint>
</series>
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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adaptor Proteins, Signal Transducing (metabolism)</term>
<term>Casein Kinase II (genetics)</term>
<term>Casein Kinase II (metabolism)</term>
<term>Casein Kinase II (physiology)</term>
<term>Eukaryotic Initiation Factor-2 (metabolism)</term>
<term>Eukaryotic Initiation Factor-2 (physiology)</term>
<term>Eukaryotic Initiation Factor-4F (metabolism)</term>
<term>Gene Expression Regulation</term>
<term>HEK293 Cells</term>
<term>Humans</term>
<term>MCF-7 Cells</term>
<term>Models, Genetic</term>
<term>Multiprotein Complexes (genetics)</term>
<term>Multiprotein Complexes (metabolism)</term>
<term>Multiprotein Complexes (physiology)</term>
<term>Oncogene Proteins (metabolism)</term>
<term>Peptide Chain Initiation, Translational</term>
<term>Phosphorylation</term>
<term>Signal Transduction</term>
<term>Stress, Physiological</term>
<term>TOR Serine-Threonine Kinases (genetics)</term>
<term>TOR Serine-Threonine Kinases (metabolism)</term>
<term>TOR Serine-Threonine Kinases (physiology)</term>
<term>Ternary Complex Factors (metabolism)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Casein Kinase II (génétique)</term>
<term>Casein Kinase II (métabolisme)</term>
<term>Casein Kinase II (physiologie)</term>
<term>Cellules HEK293</term>
<term>Cellules MCF-7</term>
<term>Complexes multiprotéiques (génétique)</term>
<term>Complexes multiprotéiques (métabolisme)</term>
<term>Complexes multiprotéiques (physiologie)</term>
<term>Facteur-2 d'initiation eucaryote (métabolisme)</term>
<term>Facteur-2 d'initiation eucaryote (physiologie)</term>
<term>Facteur-4F d'initiation eucaryote (métabolisme)</term>
<term>Facteurs du complexe ternaire (métabolisme)</term>
<term>Humains</term>
<term>Initiation de la traduction</term>
<term>Modèles génétiques</term>
<term>Phosphorylation</term>
<term>Protéines adaptatrices de la transduction du signal (métabolisme)</term>
<term>Protéines oncogènes (métabolisme)</term>
<term>Régulation de l'expression des gènes</term>
<term>Stress physiologique</term>
<term>Sérine-thréonine kinases TOR (génétique)</term>
<term>Sérine-thréonine kinases TOR (métabolisme)</term>
<term>Sérine-thréonine kinases TOR (physiologie)</term>
<term>Transduction du signal</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Casein Kinase II</term>
<term>Multiprotein Complexes</term>
<term>TOR Serine-Threonine Kinases</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Adaptor Proteins, Signal Transducing</term>
<term>Casein Kinase II</term>
<term>Eukaryotic Initiation Factor-2</term>
<term>Eukaryotic Initiation Factor-4F</term>
<term>Multiprotein Complexes</term>
<term>Oncogene Proteins</term>
<term>TOR Serine-Threonine Kinases</term>
<term>Ternary Complex Factors</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="physiology" xml:lang="en"><term>Casein Kinase II</term>
<term>Eukaryotic Initiation Factor-2</term>
<term>Multiprotein Complexes</term>
<term>TOR Serine-Threonine Kinases</term>
</keywords>
<keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Casein Kinase II</term>
<term>Complexes multiprotéiques</term>
<term>Sérine-thréonine kinases TOR</term>
</keywords>
<keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Casein Kinase II</term>
<term>Complexes multiprotéiques</term>
<term>Facteur-2 d'initiation eucaryote</term>
<term>Facteur-4F d'initiation eucaryote</term>
<term>Facteurs du complexe ternaire</term>
<term>Protéines adaptatrices de la transduction du signal</term>
<term>Protéines oncogènes</term>
<term>Sérine-thréonine kinases TOR</term>
</keywords>
<keywords scheme="MESH" qualifier="physiologie" xml:lang="fr"><term>Casein Kinase II</term>
<term>Complexes multiprotéiques</term>
<term>Facteur-2 d'initiation eucaryote</term>
<term>Sérine-thréonine kinases TOR</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Gene Expression Regulation</term>
<term>HEK293 Cells</term>
<term>Humans</term>
<term>MCF-7 Cells</term>
<term>Models, Genetic</term>
<term>Peptide Chain Initiation, Translational</term>
<term>Phosphorylation</term>
<term>Signal Transduction</term>
<term>Stress, Physiological</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Cellules HEK293</term>
<term>Cellules MCF-7</term>
<term>Humains</term>
<term>Initiation de la traduction</term>
<term>Modèles génétiques</term>
<term>Phosphorylation</term>
<term>Régulation de l'expression des gènes</term>
<term>Stress physiologique</term>
<term>Transduction du signal</term>
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<front><div type="abstract" xml:lang="en"><p>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.</p>
</div>
</front>
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</TEI>
<double pmid="27040916"><pmc><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">mTORC1 and CK2 coordinate ternary and eIF4F complex assembly</title>
<author><name sortKey="Gandin, Valentina" sort="Gandin, Valentina" uniqKey="Gandin V" first="Valentina" last="Gandin">Valentina Gandin</name>
<affiliation wicri:level="1"><nlm:aff id="a1"><institution>Lady Davis Institute, SMBD JGH, McGill University</institution>
, Montreal, Quebec,<country>Canada</country>
H3T 1E2</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="a2"><institution>Department of Oncology, McGill University</institution>
, Montreal, Quebec,<country>Canada</country>
H3T 1E2</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="a3"><institution>Department of Biochemistry, McGill University</institution>
, Montreal, Quebec,<country>Canada</country>
H3T 1E2</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="a4"><institution>Department of Experimental Medicine, McGill University</institution>
, Montreal, Quebec,<country>Canada</country>
H3T 1E2</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Masvidal, Laia" sort="Masvidal, Laia" uniqKey="Masvidal L" first="Laia" last="Masvidal">Laia Masvidal</name>
<affiliation wicri:level="1"><nlm:aff id="a5"><institution>Department of Oncology-Pathology, Science for Life Laboratory, Karolinska Institutet</institution>
, Stockholm 171 76,<country>Sweden</country>
</nlm:aff>
<country xml:lang="fr">Suède</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Cargnello, Marie" sort="Cargnello, Marie" uniqKey="Cargnello M" first="Marie" last="Cargnello">Marie Cargnello</name>
<affiliation wicri:level="1"><nlm:aff id="a1"><institution>Lady Davis Institute, SMBD JGH, McGill University</institution>
, Montreal, Quebec,<country>Canada</country>
H3T 1E2</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="a2"><institution>Department of Oncology, McGill University</institution>
, Montreal, Quebec,<country>Canada</country>
H3T 1E2</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="a3"><institution>Department of Biochemistry, McGill University</institution>
, Montreal, Quebec,<country>Canada</country>
H3T 1E2</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="a4"><institution>Department of Experimental Medicine, McGill University</institution>
, Montreal, Quebec,<country>Canada</country>
H3T 1E2</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Gyenis, Laszlo" sort="Gyenis, Laszlo" uniqKey="Gyenis L" first="Laszlo" last="Gyenis">Laszlo Gyenis</name>
<affiliation wicri:level="1"><nlm:aff id="a6"><institution>Departments of Biochemistry and Oncology, Schulich School of Medicine & Dentistry, Western University, London</institution>
, Ontario,<country>Canada</country>
N6A 4L6</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Mclaughlan, Shannon" sort="Mclaughlan, Shannon" uniqKey="Mclaughlan S" first="Shannon" last="Mclaughlan">Shannon Mclaughlan</name>
<affiliation wicri:level="1"><nlm:aff id="a1"><institution>Lady Davis Institute, SMBD JGH, McGill University</institution>
, Montreal, Quebec,<country>Canada</country>
H3T 1E2</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="a2"><institution>Department of Oncology, McGill University</institution>
, Montreal, Quebec,<country>Canada</country>
H3T 1E2</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="a3"><institution>Department of Biochemistry, McGill University</institution>
, Montreal, Quebec,<country>Canada</country>
H3T 1E2</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="a4"><institution>Department of Experimental Medicine, McGill University</institution>
, Montreal, Quebec,<country>Canada</country>
H3T 1E2</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Cai, Yutian" sort="Cai, Yutian" uniqKey="Cai Y" first="Yutian" last="Cai">Yutian Cai</name>
<affiliation wicri:level="1"><nlm:aff id="a1"><institution>Lady Davis Institute, SMBD JGH, McGill University</institution>
, Montreal, Quebec,<country>Canada</country>
H3T 1E2</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="a3"><institution>Department of Biochemistry, McGill University</institution>
, Montreal, Quebec,<country>Canada</country>
H3T 1E2</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Tenkerian, Clara" sort="Tenkerian, Clara" uniqKey="Tenkerian C" first="Clara" last="Tenkerian">Clara Tenkerian</name>
<affiliation wicri:level="1"><nlm:aff id="a1"><institution>Lady Davis Institute, SMBD JGH, McGill University</institution>
, Montreal, Quebec,<country>Canada</country>
H3T 1E2</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="a6"><institution>Departments of Biochemistry and Oncology, Schulich School of Medicine & Dentistry, Western University, London</institution>
, Ontario,<country>Canada</country>
N6A 4L6</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Morita, Masahiro" sort="Morita, Masahiro" uniqKey="Morita M" first="Masahiro" last="Morita">Masahiro Morita</name>
<affiliation wicri:level="1"><nlm:aff id="a3"><institution>Department of Biochemistry, McGill University</institution>
, Montreal, Quebec,<country>Canada</country>
H3T 1E2</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Balanathan, Preetika" sort="Balanathan, Preetika" uniqKey="Balanathan P" first="Preetika" last="Balanathan">Preetika Balanathan</name>
<affiliation wicri:level="1"><nlm:aff id="a7"><institution>Cancer Program, Biomedicine Discovery Institute and Department of Anatomy and Developmental Biology, Monash University</institution>
, Victoria 3168,<country>Australia</country>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Jean Jean, Olivier" sort="Jean Jean, Olivier" uniqKey="Jean Jean O" first="Olivier" last="Jean-Jean">Olivier Jean-Jean</name>
<affiliation wicri:level="1"><nlm:aff id="a8"><institution>UPMC Univ Paris 06, CNRS-UMR8256</institution>
, Paris 75005,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Stambolic, Vuk" sort="Stambolic, Vuk" uniqKey="Stambolic V" first="Vuk" last="Stambolic">Vuk Stambolic</name>
<affiliation wicri:level="1"><nlm:aff id="a9"><institution>Princess Margaret Cancer Centre, University Health Network, and the Department of Medical Biophysics, University of Toronto</institution>
, Toronto, Ontario,<country>Canada</country>
M5G 1L7</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Trost, Matthias" sort="Trost, Matthias" uniqKey="Trost M" first="Matthias" last="Trost">Matthias Trost</name>
<affiliation wicri:level="1"><nlm:aff id="a10"><institution>MRC Protein Phosphorylation and Ubiquitylation Unit, University of Dundee</institution>
, Scotland DD1 5EH,<country>UK</country>
</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Furic, Luc" sort="Furic, Luc" uniqKey="Furic L" first="Luc" last="Furic">Luc Furic</name>
<affiliation wicri:level="1"><nlm:aff id="a7"><institution>Cancer Program, Biomedicine Discovery Institute and Department of Anatomy and Developmental Biology, Monash University</institution>
, Victoria 3168,<country>Australia</country>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Larose, Louise" sort="Larose, Louise" uniqKey="Larose L" first="Louise" last="Larose">Louise Larose</name>
<affiliation wicri:level="1"><nlm:aff id="a11"><institution>Department of Medicine, Polypeptide Laboratory, McGill University and The Research Institute of McGill University Health Centre</institution>
, Montreal, Quebec,<country>Canada</country>
H3A 2B2</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Koromilas, Antonis E" sort="Koromilas, Antonis E" uniqKey="Koromilas A" first="Antonis E." last="Koromilas">Antonis E. Koromilas</name>
<affiliation wicri:level="1"><nlm:aff id="a1"><institution>Lady Davis Institute, SMBD JGH, McGill University</institution>
, Montreal, Quebec,<country>Canada</country>
H3T 1E2</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="a4"><institution>Department of Experimental Medicine, McGill University</institution>
, Montreal, Quebec,<country>Canada</country>
H3T 1E2</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="a6"><institution>Departments of Biochemistry and Oncology, Schulich School of Medicine & Dentistry, Western University, London</institution>
, Ontario,<country>Canada</country>
N6A 4L6</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Asano, Katsura" sort="Asano, Katsura" uniqKey="Asano K" first="Katsura" last="Asano">Katsura Asano</name>
<affiliation wicri:level="1"><nlm:aff id="a12"><institution>Molecular Cellular and Developmental Biology Program, Division of Biology, Kansas State University</institution>
, Manhattan, Kansas 66506,<country>USA</country>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Litchfield, David" sort="Litchfield, David" uniqKey="Litchfield D" first="David" last="Litchfield">David Litchfield</name>
<affiliation wicri:level="1"><nlm:aff id="a6"><institution>Departments of Biochemistry and Oncology, Schulich School of Medicine & Dentistry, Western University, London</institution>
, Ontario,<country>Canada</country>
N6A 4L6</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Larsson, Ola" sort="Larsson, Ola" uniqKey="Larsson O" first="Ola" last="Larsson">Ola Larsson</name>
<affiliation wicri:level="1"><nlm:aff id="a5"><institution>Department of Oncology-Pathology, Science for Life Laboratory, Karolinska Institutet</institution>
, Stockholm 171 76,<country>Sweden</country>
</nlm:aff>
<country xml:lang="fr">Suède</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Topisirovic, Ivan" sort="Topisirovic, Ivan" uniqKey="Topisirovic I" first="Ivan" last="Topisirovic">Ivan Topisirovic</name>
<affiliation wicri:level="1"><nlm:aff id="a1"><institution>Lady Davis Institute, SMBD JGH, McGill University</institution>
, Montreal, Quebec,<country>Canada</country>
H3T 1E2</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="a2"><institution>Department of Oncology, McGill University</institution>
, Montreal, Quebec,<country>Canada</country>
H3T 1E2</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="a3"><institution>Department of Biochemistry, McGill University</institution>
, Montreal, Quebec,<country>Canada</country>
H3T 1E2</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="a4"><institution>Department of Experimental Medicine, McGill University</institution>
, Montreal, Quebec,<country>Canada</country>
H3T 1E2</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PMC</idno>
<idno type="pmid">27040916</idno>
<idno type="pmc">4822005</idno>
<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4822005</idno>
<idno type="RBID">PMC:4822005</idno>
<idno type="doi">10.1038/ncomms11127</idno>
<date when="2016">2016</date>
<idno type="wicri:Area/Pmc/Corpus">000765</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000765</idno>
<idno type="wicri:Area/Pmc/Curation">000764</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000764</idno>
<idno type="wicri:Area/Pmc/Checkpoint">000481</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000481</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">mTORC1 and CK2 coordinate ternary and eIF4F complex assembly</title>
<author><name sortKey="Gandin, Valentina" sort="Gandin, Valentina" uniqKey="Gandin V" first="Valentina" last="Gandin">Valentina Gandin</name>
<affiliation wicri:level="1"><nlm:aff id="a1"><institution>Lady Davis Institute, SMBD JGH, McGill University</institution>
, Montreal, Quebec,<country>Canada</country>
H3T 1E2</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="a2"><institution>Department of Oncology, McGill University</institution>
, Montreal, Quebec,<country>Canada</country>
H3T 1E2</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="a3"><institution>Department of Biochemistry, McGill University</institution>
, Montreal, Quebec,<country>Canada</country>
H3T 1E2</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="a4"><institution>Department of Experimental Medicine, McGill University</institution>
, Montreal, Quebec,<country>Canada</country>
H3T 1E2</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Masvidal, Laia" sort="Masvidal, Laia" uniqKey="Masvidal L" first="Laia" last="Masvidal">Laia Masvidal</name>
<affiliation wicri:level="1"><nlm:aff id="a5"><institution>Department of Oncology-Pathology, Science for Life Laboratory, Karolinska Institutet</institution>
, Stockholm 171 76,<country>Sweden</country>
</nlm:aff>
<country xml:lang="fr">Suède</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Cargnello, Marie" sort="Cargnello, Marie" uniqKey="Cargnello M" first="Marie" last="Cargnello">Marie Cargnello</name>
<affiliation wicri:level="1"><nlm:aff id="a1"><institution>Lady Davis Institute, SMBD JGH, McGill University</institution>
, Montreal, Quebec,<country>Canada</country>
H3T 1E2</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="a2"><institution>Department of Oncology, McGill University</institution>
, Montreal, Quebec,<country>Canada</country>
H3T 1E2</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="a3"><institution>Department of Biochemistry, McGill University</institution>
, Montreal, Quebec,<country>Canada</country>
H3T 1E2</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="a4"><institution>Department of Experimental Medicine, McGill University</institution>
, Montreal, Quebec,<country>Canada</country>
H3T 1E2</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Gyenis, Laszlo" sort="Gyenis, Laszlo" uniqKey="Gyenis L" first="Laszlo" last="Gyenis">Laszlo Gyenis</name>
<affiliation wicri:level="1"><nlm:aff id="a6"><institution>Departments of Biochemistry and Oncology, Schulich School of Medicine & Dentistry, Western University, London</institution>
, Ontario,<country>Canada</country>
N6A 4L6</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Mclaughlan, Shannon" sort="Mclaughlan, Shannon" uniqKey="Mclaughlan S" first="Shannon" last="Mclaughlan">Shannon Mclaughlan</name>
<affiliation wicri:level="1"><nlm:aff id="a1"><institution>Lady Davis Institute, SMBD JGH, McGill University</institution>
, Montreal, Quebec,<country>Canada</country>
H3T 1E2</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="a2"><institution>Department of Oncology, McGill University</institution>
, Montreal, Quebec,<country>Canada</country>
H3T 1E2</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="a3"><institution>Department of Biochemistry, McGill University</institution>
, Montreal, Quebec,<country>Canada</country>
H3T 1E2</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="a4"><institution>Department of Experimental Medicine, McGill University</institution>
, Montreal, Quebec,<country>Canada</country>
H3T 1E2</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Cai, Yutian" sort="Cai, Yutian" uniqKey="Cai Y" first="Yutian" last="Cai">Yutian Cai</name>
<affiliation wicri:level="1"><nlm:aff id="a1"><institution>Lady Davis Institute, SMBD JGH, McGill University</institution>
, Montreal, Quebec,<country>Canada</country>
H3T 1E2</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="a3"><institution>Department of Biochemistry, McGill University</institution>
, Montreal, Quebec,<country>Canada</country>
H3T 1E2</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Tenkerian, Clara" sort="Tenkerian, Clara" uniqKey="Tenkerian C" first="Clara" last="Tenkerian">Clara Tenkerian</name>
<affiliation wicri:level="1"><nlm:aff id="a1"><institution>Lady Davis Institute, SMBD JGH, McGill University</institution>
, Montreal, Quebec,<country>Canada</country>
H3T 1E2</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="a6"><institution>Departments of Biochemistry and Oncology, Schulich School of Medicine & Dentistry, Western University, London</institution>
, Ontario,<country>Canada</country>
N6A 4L6</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Morita, Masahiro" sort="Morita, Masahiro" uniqKey="Morita M" first="Masahiro" last="Morita">Masahiro Morita</name>
<affiliation wicri:level="1"><nlm:aff id="a3"><institution>Department of Biochemistry, McGill University</institution>
, Montreal, Quebec,<country>Canada</country>
H3T 1E2</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Balanathan, Preetika" sort="Balanathan, Preetika" uniqKey="Balanathan P" first="Preetika" last="Balanathan">Preetika Balanathan</name>
<affiliation wicri:level="1"><nlm:aff id="a7"><institution>Cancer Program, Biomedicine Discovery Institute and Department of Anatomy and Developmental Biology, Monash University</institution>
, Victoria 3168,<country>Australia</country>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Jean Jean, Olivier" sort="Jean Jean, Olivier" uniqKey="Jean Jean O" first="Olivier" last="Jean-Jean">Olivier Jean-Jean</name>
<affiliation wicri:level="1"><nlm:aff id="a8"><institution>UPMC Univ Paris 06, CNRS-UMR8256</institution>
, Paris 75005,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Stambolic, Vuk" sort="Stambolic, Vuk" uniqKey="Stambolic V" first="Vuk" last="Stambolic">Vuk Stambolic</name>
<affiliation wicri:level="1"><nlm:aff id="a9"><institution>Princess Margaret Cancer Centre, University Health Network, and the Department of Medical Biophysics, University of Toronto</institution>
, Toronto, Ontario,<country>Canada</country>
M5G 1L7</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Trost, Matthias" sort="Trost, Matthias" uniqKey="Trost M" first="Matthias" last="Trost">Matthias Trost</name>
<affiliation wicri:level="1"><nlm:aff id="a10"><institution>MRC Protein Phosphorylation and Ubiquitylation Unit, University of Dundee</institution>
, Scotland DD1 5EH,<country>UK</country>
</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Furic, Luc" sort="Furic, Luc" uniqKey="Furic L" first="Luc" last="Furic">Luc Furic</name>
<affiliation wicri:level="1"><nlm:aff id="a7"><institution>Cancer Program, Biomedicine Discovery Institute and Department of Anatomy and Developmental Biology, Monash University</institution>
, Victoria 3168,<country>Australia</country>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Larose, Louise" sort="Larose, Louise" uniqKey="Larose L" first="Louise" last="Larose">Louise Larose</name>
<affiliation wicri:level="1"><nlm:aff id="a11"><institution>Department of Medicine, Polypeptide Laboratory, McGill University and The Research Institute of McGill University Health Centre</institution>
, Montreal, Quebec,<country>Canada</country>
H3A 2B2</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Koromilas, Antonis E" sort="Koromilas, Antonis E" uniqKey="Koromilas A" first="Antonis E." last="Koromilas">Antonis E. Koromilas</name>
<affiliation wicri:level="1"><nlm:aff id="a1"><institution>Lady Davis Institute, SMBD JGH, McGill University</institution>
, Montreal, Quebec,<country>Canada</country>
H3T 1E2</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="a4"><institution>Department of Experimental Medicine, McGill University</institution>
, Montreal, Quebec,<country>Canada</country>
H3T 1E2</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="a6"><institution>Departments of Biochemistry and Oncology, Schulich School of Medicine & Dentistry, Western University, London</institution>
, Ontario,<country>Canada</country>
N6A 4L6</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Asano, Katsura" sort="Asano, Katsura" uniqKey="Asano K" first="Katsura" last="Asano">Katsura Asano</name>
<affiliation wicri:level="1"><nlm:aff id="a12"><institution>Molecular Cellular and Developmental Biology Program, Division of Biology, Kansas State University</institution>
, Manhattan, Kansas 66506,<country>USA</country>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Litchfield, David" sort="Litchfield, David" uniqKey="Litchfield D" first="David" last="Litchfield">David Litchfield</name>
<affiliation wicri:level="1"><nlm:aff id="a6"><institution>Departments of Biochemistry and Oncology, Schulich School of Medicine & Dentistry, Western University, London</institution>
, Ontario,<country>Canada</country>
N6A 4L6</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Larsson, Ola" sort="Larsson, Ola" uniqKey="Larsson O" first="Ola" last="Larsson">Ola Larsson</name>
<affiliation wicri:level="1"><nlm:aff id="a5"><institution>Department of Oncology-Pathology, Science for Life Laboratory, Karolinska Institutet</institution>
, Stockholm 171 76,<country>Sweden</country>
</nlm:aff>
<country xml:lang="fr">Suède</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Topisirovic, Ivan" sort="Topisirovic, Ivan" uniqKey="Topisirovic I" first="Ivan" last="Topisirovic">Ivan Topisirovic</name>
<affiliation wicri:level="1"><nlm:aff id="a1"><institution>Lady Davis Institute, SMBD JGH, McGill University</institution>
, Montreal, Quebec,<country>Canada</country>
H3T 1E2</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="a2"><institution>Department of Oncology, McGill University</institution>
, Montreal, Quebec,<country>Canada</country>
H3T 1E2</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="a3"><institution>Department of Biochemistry, McGill University</institution>
, Montreal, Quebec,<country>Canada</country>
H3T 1E2</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="a4"><institution>Department of Experimental Medicine, McGill University</institution>
, Montreal, Quebec,<country>Canada</country>
H3T 1E2</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
</analytic>
<series><title level="j">Nature Communications</title>
<idno type="eISSN">2041-1723</idno>
<imprint><date when="2016">2016</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass></textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><p>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.</p>
</div>
</front>
<back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Sonenberg, N" uniqKey="Sonenberg N">N. Sonenberg</name>
</author>
<author><name sortKey="Hinnebusch, A G" uniqKey="Hinnebusch A">A. G. Hinnebusch</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Hinnebusch, A G" uniqKey="Hinnebusch A">A. G. Hinnebusch</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Albert, V" uniqKey="Albert V">V. Albert</name>
</author>
<author><name sortKey="Hall, M N" uniqKey="Hall M">M. N. Hall</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Koromilas, A E" uniqKey="Koromilas A">A. E. Koromilas</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Baird, T D" uniqKey="Baird T">T. D. Baird</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Gandin, V" uniqKey="Gandin V">V. Gandin</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Thoreen, C C" uniqKey="Thoreen C">C. C. Thoreen</name>
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</analytic>
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<pubmed><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">mTORC1 and CK2 coordinate ternary and eIF4F complex assembly.</title>
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<author><name sortKey="Tenkerian, Clara" sort="Tenkerian, Clara" uniqKey="Tenkerian C" first="Clara" last="Tenkerian">Clara Tenkerian</name>
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<author><name sortKey="Asano, Katsura" sort="Asano, Katsura" uniqKey="Asano K" first="Katsura" last="Asano">Katsura Asano</name>
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<author><name sortKey="Topisirovic, Ivan" sort="Topisirovic, Ivan" uniqKey="Topisirovic I" first="Ivan" last="Topisirovic">Ivan Topisirovic</name>
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<author><name sortKey="Gandin, Valentina" sort="Gandin, Valentina" uniqKey="Gandin V" first="Valentina" last="Gandin">Valentina Gandin</name>
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</author>
<author><name sortKey="Masvidal, Laia" sort="Masvidal, Laia" uniqKey="Masvidal L" first="Laia" last="Masvidal">Laia Masvidal</name>
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</affiliation>
</author>
<author><name sortKey="Cargnello, Marie" sort="Cargnello, Marie" uniqKey="Cargnello M" first="Marie" last="Cargnello">Marie Cargnello</name>
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</placeName>
</affiliation>
</author>
<author><name sortKey="Gyenis, Laszlo" sort="Gyenis, Laszlo" uniqKey="Gyenis L" first="Laszlo" last="Gyenis">Laszlo Gyenis</name>
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<wicri:regionArea>Departments of Biochemistry and Oncology, Schulich School of Medicine &Dentistry, Western University, London, Ontario</wicri:regionArea>
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</author>
<author><name sortKey="Mclaughlan, Shannon" sort="Mclaughlan, Shannon" uniqKey="Mclaughlan S" first="Shannon" last="Mclaughlan">Shannon Mclaughlan</name>
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</placeName>
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<author><name sortKey="Cai, Yutian" sort="Cai, Yutian" uniqKey="Cai Y" first="Yutian" last="Cai">Yutian Cai</name>
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</author>
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<author><name sortKey="Jean Jean, Olivier" sort="Jean Jean, Olivier" uniqKey="Jean Jean O" first="Olivier" last="Jean-Jean">Olivier Jean-Jean</name>
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</placeName>
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<author><name sortKey="Stambolic, Vuk" sort="Stambolic, Vuk" uniqKey="Stambolic V" first="Vuk" last="Stambolic">Vuk Stambolic</name>
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<author><name sortKey="Trost, Matthias" sort="Trost, Matthias" uniqKey="Trost M" first="Matthias" last="Trost">Matthias Trost</name>
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<author><name sortKey="Furic, Luc" sort="Furic, Luc" uniqKey="Furic L" first="Luc" last="Furic">Luc Furic</name>
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<author><name sortKey="Larose, Louise" sort="Larose, Louise" uniqKey="Larose L" first="Louise" last="Larose">Louise Larose</name>
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</author>
<author><name sortKey="Koromilas, Antonis E" sort="Koromilas, Antonis E" uniqKey="Koromilas A" first="Antonis E" last="Koromilas">Antonis E. Koromilas</name>
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</author>
<author><name sortKey="Asano, Katsura" sort="Asano, Katsura" uniqKey="Asano K" first="Katsura" last="Asano">Katsura Asano</name>
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<country xml:lang="fr">États-Unis</country>
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<author><name sortKey="Litchfield, David" sort="Litchfield, David" uniqKey="Litchfield D" first="David" last="Litchfield">David Litchfield</name>
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<author><name sortKey="Larsson, Ola" sort="Larsson, Ola" uniqKey="Larsson O" first="Ola" last="Larsson">Ola Larsson</name>
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<country xml:lang="fr">Suède</country>
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<author><name sortKey="Topisirovic, Ivan" sort="Topisirovic, Ivan" uniqKey="Topisirovic I" first="Ivan" last="Topisirovic">Ivan Topisirovic</name>
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<series><title level="j">Nature communications</title>
<idno type="eISSN">2041-1723</idno>
<imprint><date when="2016" type="published">2016</date>
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<term>Casein Kinase II (metabolism)</term>
<term>Casein Kinase II (physiology)</term>
<term>Eukaryotic Initiation Factor-2 (metabolism)</term>
<term>Eukaryotic Initiation Factor-2 (physiology)</term>
<term>Eukaryotic Initiation Factor-4F (metabolism)</term>
<term>Gene Expression Regulation</term>
<term>HEK293 Cells</term>
<term>Humans</term>
<term>MCF-7 Cells</term>
<term>Models, Genetic</term>
<term>Multiprotein Complexes (genetics)</term>
<term>Multiprotein Complexes (metabolism)</term>
<term>Multiprotein Complexes (physiology)</term>
<term>Oncogene Proteins (metabolism)</term>
<term>Peptide Chain Initiation, Translational</term>
<term>Phosphorylation</term>
<term>Signal Transduction</term>
<term>Stress, Physiological</term>
<term>TOR Serine-Threonine Kinases (genetics)</term>
<term>TOR Serine-Threonine Kinases (metabolism)</term>
<term>TOR Serine-Threonine Kinases (physiology)</term>
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<term>Casein Kinase II (métabolisme)</term>
<term>Casein Kinase II (physiologie)</term>
<term>Cellules HEK293</term>
<term>Cellules MCF-7</term>
<term>Complexes multiprotéiques (génétique)</term>
<term>Complexes multiprotéiques (métabolisme)</term>
<term>Complexes multiprotéiques (physiologie)</term>
<term>Facteur-2 d'initiation eucaryote (métabolisme)</term>
<term>Facteur-2 d'initiation eucaryote (physiologie)</term>
<term>Facteur-4F d'initiation eucaryote (métabolisme)</term>
<term>Facteurs du complexe ternaire (métabolisme)</term>
<term>Humains</term>
<term>Initiation de la traduction</term>
<term>Modèles génétiques</term>
<term>Phosphorylation</term>
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<term>Protéines oncogènes (métabolisme)</term>
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<term>Facteur-4F d'initiation eucaryote</term>
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<term>HEK293 Cells</term>
<term>Humans</term>
<term>MCF-7 Cells</term>
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<term>Peptide Chain Initiation, Translational</term>
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<term>Humains</term>
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<term>Modèles génétiques</term>
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<front><div type="abstract" xml:lang="en">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.</div>
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