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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Format: | Article |
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Public Library of Science (PLoS)
2010-02-01
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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. |
first_indexed | 2024-04-14T08:31:22Z |
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id | doaj.art-a881bb787ee243a3b48edcf721b59ea8 |
institution | Directory Open Access Journal |
issn | 1932-6203 |
language | English |
last_indexed | 2024-04-14T08:31:22Z |
publishDate | 2010-02-01 |
publisher | Public Library of Science (PLoS) |
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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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