The translation regulatory subunit eIF3f controls the kinase-dependent mTOR signaling required for muscle differentiation and hypertrophy in mouse.

The mTORC1 pathway is required for both the terminal muscle differentiation and hypertrophy by controlling the mammalian translational machinery via phosphorylation of S6K1 and 4E-BP1. mTOR and S6K1 are connected by interacting with the eIF3 initiation complex. The regulatory subunit eIF3f plays a m...

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Main Authors: Alfredo Csibi, Karen Cornille, Marie-Pierre Leibovitch, Anne Poupon, Lionel A Tintignac, Anthony M J Sanchez, Serge A Leibovitch
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2010-02-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC2813880?pdf=render
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author Alfredo Csibi
Karen Cornille
Marie-Pierre Leibovitch
Anne Poupon
Lionel A Tintignac
Anthony M J Sanchez
Serge A Leibovitch
author_facet Alfredo Csibi
Karen Cornille
Marie-Pierre Leibovitch
Anne Poupon
Lionel A Tintignac
Anthony M J Sanchez
Serge A Leibovitch
author_sort Alfredo Csibi
collection DOAJ
description The mTORC1 pathway is required for both the terminal muscle differentiation and hypertrophy by controlling the mammalian translational machinery via phosphorylation of S6K1 and 4E-BP1. mTOR and S6K1 are connected by interacting with the eIF3 initiation complex. The regulatory subunit eIF3f plays a major role in muscle hypertrophy and is a key target that accounts for MAFbx function during atrophy. Here we present evidence that in MAFbx-induced atrophy the degradation of eIF3f suppresses S6K1 activation by mTOR, whereas an eIF3f mutant insensitive to MAFbx polyubiquitination maintained persistent phosphorylation of S6K1 and rpS6. During terminal muscle differentiation a conserved TOS motif in eIF3f connects mTOR/raptor complex, which phosphorylates S6K1 and regulates downstream effectors of mTOR and Cap-dependent translation initiation. Thus eIF3f plays a major role for proper activity of mTORC1 to regulate skeletal muscle size.
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spelling doaj.art-a881bb787ee243a3b48edcf721b59ea82022-12-22T02:03:54ZengPublic Library of Science (PLoS)PLoS ONE1932-62032010-02-0152e899410.1371/journal.pone.0008994The translation regulatory subunit eIF3f controls the kinase-dependent mTOR signaling required for muscle differentiation and hypertrophy in mouse.Alfredo CsibiKaren CornilleMarie-Pierre LeibovitchAnne PouponLionel A TintignacAnthony M J SanchezSerge A LeibovitchThe mTORC1 pathway is required for both the terminal muscle differentiation and hypertrophy by controlling the mammalian translational machinery via phosphorylation of S6K1 and 4E-BP1. mTOR and S6K1 are connected by interacting with the eIF3 initiation complex. The regulatory subunit eIF3f plays a major role in muscle hypertrophy and is a key target that accounts for MAFbx function during atrophy. Here we present evidence that in MAFbx-induced atrophy the degradation of eIF3f suppresses S6K1 activation by mTOR, whereas an eIF3f mutant insensitive to MAFbx polyubiquitination maintained persistent phosphorylation of S6K1 and rpS6. During terminal muscle differentiation a conserved TOS motif in eIF3f connects mTOR/raptor complex, which phosphorylates S6K1 and regulates downstream effectors of mTOR and Cap-dependent translation initiation. Thus eIF3f plays a major role for proper activity of mTORC1 to regulate skeletal muscle size.http://europepmc.org/articles/PMC2813880?pdf=render
spellingShingle Alfredo Csibi
Karen Cornille
Marie-Pierre Leibovitch
Anne Poupon
Lionel A Tintignac
Anthony M J Sanchez
Serge A Leibovitch
The translation regulatory subunit eIF3f controls the kinase-dependent mTOR signaling required for muscle differentiation and hypertrophy in mouse.
PLoS ONE
title The translation regulatory subunit eIF3f controls the kinase-dependent mTOR signaling required for muscle differentiation and hypertrophy in mouse.
title_full The translation regulatory subunit eIF3f controls the kinase-dependent mTOR signaling required for muscle differentiation and hypertrophy in mouse.
title_fullStr The translation regulatory subunit eIF3f controls the kinase-dependent mTOR signaling required for muscle differentiation and hypertrophy in mouse.
title_full_unstemmed The translation regulatory subunit eIF3f controls the kinase-dependent mTOR signaling required for muscle differentiation and hypertrophy in mouse.
title_short The translation regulatory subunit eIF3f controls the kinase-dependent mTOR signaling required for muscle differentiation and hypertrophy in mouse.
title_sort translation regulatory subunit eif3f controls the kinase dependent mtor signaling required for muscle differentiation and hypertrophy in mouse
url http://europepmc.org/articles/PMC2813880?pdf=render
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